*****ANNALS OF THORACIC SURGERY*****
(REFERENCE 1 OF 102) 97219107
Chen EP Bittner HB Davis RD Jr Van Trigt P 3rd Milrinone improves pulmonary hemodynamics and right ventricular function in chronic pulmonary hypertension.
In: Ann Thorac Surg (1997 Mar) 63(3):814-21
ISSN: 0003-4975
BACKGROUND: Right ventricular failure after cardiac transplantation is commonly related to preexisting recipient pulmonary hypertension. This study was designed to investigate the effects of intravenous milrinone on pulmonary hemodynamic indices and right ventricular function in a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. METHODS: Eight mongrel dogs underwent pulmonary artery catheterization to measure right-sided hemodynamic indices before and 6 weeks after a right atrial injection of monocrotaline pyrrole. Six weeks after injection, all hearts were instrumented with a pulmonary artery flow probe, ultrasonic dimension transducers, and micromanometers. Data were collected at baseline and after milrinone infusion. RESULTS: Six weeks after monocrotaline pyrrole injection, significant increases in the pulmonary artery pressure and pulmonary vascular resistance were observed. Milrinone led to significant increases in right ventricular function as well as significant improvements in pulmonary vascular resistance, pulmonary blood flow, and left ventricular filling. CONCLUSIONS: This investigation demonstrates the well-known hemodynamic and inotropic effects of milrinone which, in the setting of monocrotaline pyrrole- induced pulmonary hypertension, were also associated with significant increases in pulmonary blood flow and left ventricular filling.
Registry Numbers: 23291-96-5 (monocrotaline pyrrole) 315-22-0 (Monocrotaline) 78415-72-2 (milrinone)
Institutional address: Department of Surgery Duke University Medical Center Durham North Carolina USA.
(REFERENCE 2 OF 102) 97219106
Chen EP Bittner HB Craig DM Davis RD Jr Van Trigt P 3rd Pulmonary hemodynamics and blood flow characteristics in chronic pulmonary hypertension.
In: Ann Thorac Surg (1997 Mar) 63(3):806-13
ISSN: 0003-4975
BACKGROUND: Lung transplantation is now an acceptable form of therapy for pulmonary hypertension, but controversy remains regarding the most appropriate surgical procedure. In this study, the changes in pulmonary vascular mechanics occurring in the setting of pulmonary hypertension were investigated using an adult canine model of monocrotaline pyrrole-induced pulmonary hypertension. METHODS: Animals underwent pulmonary artery catheterization to measure right heart pressures before and 8 weeks after injection of either 3 mg/kg of monocrotaline pyrrole (n = 8) or placebo (n = 8). Eight weeks after injection, hearts underwent instrumentation with an ultrasonic flow probe and micromanometers. Harmonic derivation of functional data was achieved with Fourier analysis. RESULTS: Significant increases in mean pulmonary artery pressure and pulmonary vascular resistance were observed after monocrotaline pyrrole injection. There was no significant difference in pulmonary blood flow. However, significant increases in input resistance and right ventricular hydraulic power with significant decreases in transpulmonary efficiency were observed. CONCLUSIONS: Pulmonary hypertension causes significant alterations in pulmonary hemodynamics. Pulmonary blood flow is maintained by a significant increase in total power but with a significant decrease in transpulmonary efficiency. This adult canine model of pulmonary hypertension provides a useful means by which to evaluate surgical options of lung transplantation for improving pulmonary hemodynamics in the setting of chronic pulmonary hypertension.
Registry Numbers: 23291-96-5 (monocrotaline pyrrole) 315-22-0 (Monocrotaline)
Institutional address: Department of Surgery Duke University Medical Center Durham North Carolina USA.
(REFERENCE 3 OF 102) 97219078
Hiramatsu T Imai Y Takanashi Y Hoshino S Yashima M Tanaka SA Chang D Nakazawa M Time course of endothelin-1 and nitrate anion levels after cardiopulmonary bypass in congenital heart defects.
In: Ann Thorac Surg (1997 Mar) 63(3):648-52
ISSN: 0003-4975
BACKGROUND: The endothelium-derived vasoconstrictor endothelin-1 (ET- 1) may be involved in pulmonary hypertension (PH), but production of the endothelium-derived vasodilator nitric oxide (NO) after cardiopulmonary bypass (CPB) in congenital heart disease is unclear. METHODS: Twenty patients (age, 4 months to 12 years) were divided into three groups: severe PH (mean pulmonary-to-systemic arterial pressure ratio > 0.5) and high pulmonary flow (n = 8), mild PH (mean pulmonary-to-systemic arterial pressure ratio < 0.35) and high pulmonary flow (n = 6), and no PH and low pulmonary flow (n = 6). The mean pulmonary-to-systemic arterial pressure ratio was calculated and blood samples were taken, and NO3-, an NO metabolite, was measured. RESULTS: Levels of ET-1 in the group with severe PH and high pulmonary flow were higher than in the other groups until 6 hours after CPB, and NO3- was not changed significantly in the group with severe PH and high pulmonary flow and or the group with mild PH and high pulmonary flow during CPB. Endothelin-1 in the group with no PH and low pulmonary flow was higher than in the group with mild PH and high pulmonary flow after CPB, and NO3- in the group with no PH and low pulmonary flow significantly decreased after CPB. A positive correlation was obtained between mean pulmonary-to-systemic arterial pressure ratio and ET-1 (r = 0.742 before CPB; r = 0.689 after CPB). CONCLUSIONS: Imbalance between increased ET-1 and constant NO after CPB in the group with severe PH and high pulmonary flow could contribute to dominant effects of ET-1, which may injure the lung. The increased ET-1 and the decreased NO after CPB in the group with no PH and low pulmonary flow may induce a mechanism of protective vasoconstriction against an acute increase in pulmonary flow.
Institutional address: Department of Pediatric Cardiac Surgery Tokyo Women's Medical College Heart Institute of Japan Japan.
(REFERENCE 4 OF 102) 98014677
Mendeloff EN Huddleston CB Payne M Unusual cause of pulmonary hypertension and congestive heart failure in a newborn.
In: Ann Thorac Surg (1997 Oct) 64(4):1174-7
ISSN: 0003-4975
Anomalous systemic arterial supply to a lobe of the lung is a rare cause of pulmonary hypertension and congestive heart failure in the newborn period. We report the presentation and successful treatment of a neonate with this unusual anatomy. Proper diagnosis required both echocardiography and aortography, and surgical resection of the involved lobe was curative.
Institutional address: Department of Cardiothoracic Surgery St. Louis Children's Hospital St. Louis Missouri 63110 USA. mendeloff_e@a1kids.wustl.edu
(REFERENCE 5 OF 102) 98014663
Luciani GB Nichani S Chang AC Wells WJ Newth CJ Starnes VA Continuous versus intermittent furosemide infusion in critically ill infants after open heart operations.
In: Ann Thorac Surg (1997 Oct) 64(4):1133-9
ISSN: 0003-4975
BACKGROUND: Use of intravenous furosemide is generally avoided in critically ill neonates and infants soon after open heart operations to prevent fluctuations in intravascular volume and resulting circulatory instability. METHODS: To assess and compare the safety and efficacy of continuous versus intermittent intravenous furosemide, we undertook a prospective, randomized trial in 26 consecutive patients less than 6 months of age. Inclusion criteria were presence of low-output syndrome requiring inotropic support (24/26 patients) or pulmonary hypertension requiring vasodilator therapy (10/26 patients) within 6 hours of discontinuation of cardiopulmonary bypass. Eleven patients received 0.1 mg x kg(-1) x h(- 1) continuous intravenous furosemide (group 1) and 15 received 1 mg/kg bolus every 4 hours (group 2) for 24 hours. Mean age (3.7 +/- 3.4 versus 1.8 +/- 2.5 months) and weight (4.6 +/- 2.1 versus 4.3 +/- 1.7 kg) were comparable. RESULTS: Group 2 infants showed slightly greater absolute urinary output (2.5 +/- 1.1 mL/kg per hour versus 3.3 +/- 1.1 mL/kg per hour, p = 0.05). However, urinary output per dose of drug was significantly larger in group 1 infants (1.0 +/- 0.4 versus 0.5 +/- 0.2 mL x kg(-1) x h(-1); p = 0.002) with lesser fluctuations (variance, 1.9 +/- 1.6 versus 3.8 +/- 2.1; p = 0.02) and fluid replacement needs (20.6 +/- 3.8 versus 51.8 +/- 14.4; p = 0.001). Electrolyte replacement requirements were similar. A trend toward greater hemodynamic instability in group 2 patients (heart rate variance 88.4 +/- 79.8 versus 128.3 +/- 82.7; p = 0.09; central venous pressure variance 2.8 +/- 1.90 versus 4.1 +/- 3.7; p = 0.07; mixed venous oxygen saturation variance, 32.3 +/- 27.6 versus 45.7 +/- 20.4; p = 0.06) was noted. All patients who completed the study protocol survived operation and were discharged home. CONCLUSIONS: We conclude that (1) commonly used doses of both intermittent and continuous intravenous furosemide infusion can be safely administered to critically ill neonates and infants as early as 6 hours after operation, (2) continuous infusion yields an almost comparable urinary output with a much lower dose of furosemide, and (3) intermittent administration is associated with greater fluctuations in urinary output and greater needs for fluid replacement therapy.
Registry Numbers: 54-31-9 (Furosemide)
Institutional address: Division of Cardiothoracic Surgery Childrens Hospital Los Angeles California USA.
(REFERENCE 6 OF 102) 97185653
Barzaghi N Olivei M Minzioni G Degani A Braschi A Vigano M ECMO and inhaled nitric oxide for cardiopulmonary failure after heart retransplantation.
In: Ann Thorac Surg (1997 Feb) 63(2):533-5
ISSN: 0003-4975
Cardiopulmonary failure occurred in a 62-year-old patient a few hours after emergency cardiac retransplantation. Venoarterial extracorporeal membrane oxygenation was required to support biventricular dysfunction; thereafter, inhaled nitric oxide was given for residual hypoxemia and pulmonary hypertension. We report survival after venoarterial extracorporeal membrane oxygenation and inhaled nitric oxide treatment for both heart and lung failure in a heart recipient.
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Department of Anesthesiology and Biotechnology IRCCS Policlinico San Matteo Italy.
(REFERENCE 7 OF 102) 97048824
Hartz RS Byrne JG Levitsky S Park J Rich S Predictors of mortality in pulmonary thromboendarterectomy [see comments]
In: Ann Thorac Surg (1996 Nov) 62(5):1255-9; discussion 1259-60
ISSN: 0003-4975
BACKGROUND: The operative mortality associated with surgical thromboendarterectomy of the pulmonary arteries has decreased at the University of California in San Diego with the application of new techniques. For universal performance of the procedure, however, those factors that contribute to the high operative mortality must be identified. We analyzed our results in 34 consecutive patients undergoing pulmonary thromboendarterectomy to determine those preoperative factors that contribute to operative mortality. METHODS: Since 1983, 34 patients with severe, surgically correctable chronic thromboembolic pulmonary hypertension who were judged to be operable by pulmonary arteriography underwent pulmonary thromboendarterectomy. No patient was excluded because of right ventricular failure or hemodynamic severity of disease; the mean pulmonary artery pressure (PAP) was 54 mm Hg, the mean pulmonary vascular resistance (PVR) was 1,094 dynes.s.cm-5, and all patients were in New York Heart Association functional class III or IV. RESULTS: Postoperative course was characterized either by swift recovery (mean length of stay, 13 days) or by rapid demise resulting from pulmonary or right ventricular failure, or both (overall operative mortality, 23%). In survivors, the mean PAP, PVR, cardiac output, and New York Heart Association functional class were significantly improved (p < 0.05). Patients who died had a significantly greater mean preoperative PAP than did those who survived (62.1 +/- 1.2 versus 49.5 +/- 2.3 mm Hg; p < 0.01) and significantly higher PVR (1,512 +/- 116 versus 949 +/- 85 dynes.s.cm-5; p < 0.01). In addition, both a PVR of more than 1,100 dynes.s.cm-5 and a mean PAP of more than 50 mm Hg could accurately predict operative mortality: operative mortality was six times greater in patients with a preoperative PVR of greater than 1,100 dynes.s.cm-5 (41% versus 5.85%) and almost five times greater in those with a mean PAP of greater than 50 mm Hg (37% versus 8%). No intraoperative factors, including the use or duration of circulatory arrest, affected outcome. CONCLUSIONS: Patients with severe hemodynamic disease (PVR > 1,100 dynes.s.cm-5 and PAP > 50 mm Hg) have a high likelihood of operative mortality and perhaps should not undergo pulmonary thromboendarterectomy, except at institutions where the operation is performed frequently.
Comment in: Ann Thorac Surg 1996 Nov;62(5):1253-4
Comment in: Ann Thorac Surg 1997 Sep;64(3):883-4
Institutional address: Department of Surgery University of Illinois Hospital and Clinics Chicago USA.
(REFERENCE 8 OF 102) 99091011
Zund G Pretre R Niederhauser U Vogt PR Turina MI Improved exposure of the pulmonary arteries for thromboendarterectomy.
In: Ann Thorac Surg (1998 Nov) 66(5):1821-3
ISSN: 0003-4975
Pulmonary thromboendarterectomy is a surgical technique for treating pulmonary hypertension caused by unresolved pulmonary embolism. It has been recommended to perform this procedure under deep hypothermic circulatory arrest. Here we describe two technical modifications: (1) improved exposure to the right pulmonary artery by division of the superior caval vein and (2) thromboendarterectomy in normothermic cardiopulmonary bypass, with beating heart or electrically induced ventricular fibrillation. These modifications allow complete endarterectomy of both pulmonary arteries under normothermic conditions, thus avoiding hypothermic circulatory arrest, which results in short cardiopulmonary bypass times and reduces the morbidity and mortality of this procedure.
Institutional address: Clinic for Cardiovascular Surgery University Hospital Zurich Switzerland.
(REFERENCE 9 OF 102) 99090956
Yamaki S Abe A Tabayashi K Endo M Mohri H Takahashi T Inoperable pulmonary vascular disease in infants with congenital heart disease.
In: Ann Thorac Surg (1998 Nov) 66(5):1565-70
ISSN: 0003-4975
BACKGROUND: Among 120 infants less than 12 months of age who had lung biopsy and autopsy, 20 were inoperable because of severe irreversible pulmonary vascular disease. METHODS: The infants were classified into three groups. Group 1 comprised 6 patients who showed complete obstruction of the small pulmonary arterial lumen and atrophy of the peripheral arterial media and who were considered to have absolute operative contraindications. Group 2 comprised 6 patients who had no pathologic findings of absolute operative contraindication and had an index of pulmonary vascular disease of more than 2.2. They were isolated as having advanced plexogenic pulmonary arteriopathy. Group 3 comprised 8 patients who had extremely thickened media of small pulmonary arteries, with abnormally thickened media extending into the small peripheral arteries characterized by extremely narrow lumina and medial thickness exceeding luminal diameter. RESULTS: Six of the 9 patients in whom operative repair was abandoned on the basis of preoperative or intraoperative lung biopsy are still alive. Of the 11 patients who underwent operation without biopsy, none survived. CONCLUSIONS: Preoperative or intraoperative lung biopsy and assessment of arteriopathy based on the above criteria are recommended in all patients in whom fatal pulmonary vascular disease is suspected.
Institutional address: Department of Cardiology Katta General Hospital Shiroishi Japan. s-heart@mail.cc.tohoku.ac.jp
(REFERENCE 10 OF 102) 99015454
Vitvitsky EV Griffin JP Collins MH Spray TL Gaynor JW Increased pulmonary blood flow produces endothelial cell dysfunction in neonatal swine.
In: Ann Thorac Surg (1998 Oct) 66(4):1372-7
ISSN: 0003-4975
BACKGROUND: The mechanisms by which increased pulmonary blood flow results in pulmonary hypertension have not been determined. METHODS: To determine if increased pulmonary blood flow produces endothelial dysfunction that precedes vascular remodeling and smooth muscle proliferation, neonatal swine (n = 12) (age, 6.1+/-0.5 days) underwent ligation of the left pulmonary artery (LPA) to increase blood flow to the right lung. At 12 weeks of age, endothelium- dependent vasodilatation was assessed by acetylcholine infusion and endothelium-independent vasodilatation by inhaled nitric oxide (NO) in the LPA group and age-matched controls (CON) (n = 11). RESULTS: Mean pulmonary artery pressure was 24.1+/-3.0 mm Hg in the LPA group and 20.8+/-1.9 mm Hg in the CON group (p < 0.1). Pulmonary vascular resistance was 13.2+/-2.2 Wood units in the LPA group and 5.8+/-0.8 Wood units in the CON group (p = 0.001). Acute occlusion of the left pulmonary artery in the CON group increased pulmonary vascular resistance to 6.9+/-3.9 Wood units (p = 0.04). Administration of acetylcholine in the CON group after preconstriction with the thromboxane A2 analogue U46619 resulted in a 30.6%+/-5.4% decrease in pulmonary vascular resistance. In the LPA group, acetylcholine produced paradoxical vasoconstriction and a 15.4%+/-4.1% increase in pulmonary vascular resistance (p < 0.001 versus CON) indicating loss of endothelium-dependent vasodilatation. Nitric oxide decreased pulmonary vascular resistance by 41.9%+/-3.3% in the CON group and 30.8%+/-2.7% in the LPA group (p = 0.04 versus CON), indicating preserved endothelium-independent vasodilatation in both groups. Morphometric analysis was performed in 4 animals from each group. Medial wall thickness as percent of external diameter of small arteries (<100 microm) was the same in both groups (6.4%+/-0.4% in the LPA group versus 6.6% +/-0.4% in the CON animals; p > 0.1). CONCLUSIONS: Increased pulmonary blood flow in immature animals produces endothelial cell dysfunction with loss of endothelium- dependent vasodilatation before the onset of pulmonary vascular remodeling. Subsequent smooth muscle proliferation may be mediated by endothelium-derived factors.
Institutional address: Department of Pathology The Children's Hospital of Philadelphia Pennsylvania 19104 USA.
(REFERENCE 11 OF 102) 95374073
Goldman AP Delius RE Deanfield JE Macrae DJ Nitric oxide is superior to prostacyclin for pulmonary hypertension after cardiac operations.
In: Ann Thorac Surg (1995 Aug) 60(2):300-5; discussion 306
ISSN: 0003-4975
BACKGROUND. Severe pulmonary hypertension is still a cause of morbidity and mortality in children after cardiac operations. The objective of this study was to compare the vasodilator properties of inhaled nitric oxide, a novel pulmonary vasodilator, and intravenous prostacyclin in the treatment of severe postoperative pulmonary hypertension. METHODS. Thirteen children (aged 3 days to 12 months) with severe pulmonary hypertension after cardiac operations were given inhaled nitric oxide (20 ppm x 10 minutes) and intravenous prostacyclin (20 ng.kg-1.min-1 x 10 minutes) in a prospective, randomized cross-over study. RESULTS. Both nitric oxide and prostacyclin resulted in a reduction in pulmonary arterial pressure, although the mean pulmonary arterial pressure was significantly lower during nitric oxide therapy (28.5 +/- 2.9 mm Hg) than during prostacyclin therapy (35.4 +/- 2.1 mm Hg; p < 0.05). The mean pulmonary to systemic arterial pressure ratio was also significantly lower during nitric oxide than prostacylin administration (0.46 +/- 0.04 versus 0.68 +/- 0.05; p < 0.01), due mainly to only prostacyclin lowering systemic blood pressure. CONCLUSIONS. Inhaled nitric oxide was a more effective and selective pulmonary vasodilator than prostacyclin and should be considered as the preferred treatment for severe postoperative pulmonary hypertension.
Registry Numbers: 10102-43-9 (Nitric Oxide) 35121-78-9 (Epoprostenol)
Institutional address: Cardiothoracic Unit Great Ormond Street Hospital for Children London United Kingdom.
(REFERENCE 12 OF 102) 95374068
Frist WH Lorenz CH Walker ES Loyd JE Stewart JR Graham TP Jr Pearlstein DP Key SP Merrill WH MRI complements standard assessment of right ventricular function after lung transplantation.
In: Ann Thorac Surg (1995 Aug) 60(2):268-71
ISSN: 0003-4975
BACKGROUND. Changes in right ventricular mass and ejection fraction after single-lung transplantation for pulmonary hypertension are poorly understood. METHODS. To complement functional data provided by echocardiography, radionuclide ventriculography, and right heart catheterization, magnetic resonance imaging was used to assess right ventricular function in 5 single-lung transplant recipients with preoperative pulmonary hypertension and right ventricular dysfunction (right ventricular ejection fraction, 0.21 +/- 0.09). The right and left ventricular mass, ejection fraction, and mass ratio (left ventricular mass/right ventricular mass) were calculated from the magnetic resonance images. RESULTS. The mean pulmonary artery pressure fell from 72 +/- 18 to 21 +/- 8 mm Hg after transplantation. At 3 months after transplantation both the left ventricular and right ventricular ejection fractions approached normal values, as shown by both radionuclide ventriculography and magnetic resonance imaging, but the right ventricular mass remained abnormally high with slightly low mass ratios. By 1 year both the left ventricular and right ventricular masses had regressed to normal with near-normal mass ratios. CONCLUSIONS. Right ventricular performance returns to nearly normal early after transplantation, but the right ventricular mass regresses over a more prolonged time. Cine magnetic resonance imaging provides a noninvasive means of assessing changes in right ventricular function and mass after lung transplantation.
Institutional address: Department of Cardiac and Thoracic Surgery Vanderbilt University Medical Center Nashville Tennessee USA.
(REFERENCE 13 OF 102) 95251435
Serraf A Herve P Labat C Mazmanian GM de Montpreville V Planche C Brink C Endothelial dysfunction in venous pulmonary hypertension in the neonatal piglet.
In: Ann Thorac Surg (1995 May) 59(5):1155-61
ISSN: 0003-4975
In a group of neonatal piglets an increase in pulmonary arterial pressure was obtained within 2 weeks after a partial mechanical obstruction of the left atrium by a balloon catheter. Mean pulmonary artery pressure in the hypertensive animals (n = 6) was 24 +/- 2 mm Hg as compared (p < 0.01) with 15 +/- 1 mm Hg in controls (n = 6) or 9 +/- 2 mm Hg in sham-operated piglets (n = 6). Cardiac index was reduced in hypertensive versus control and sham groups: 0.15 +/- 0.01 versus 0.32 +/- 0.05 and 0.29 +/- 0.04 L.min-1.kg-1 (p < 0.05), respectively. There was no detectable difference on histologic examination in the pulmonary arteries between the three groups. Right ventricular hypertrophy was observed in the group with pulmonary hypertension. In hypertensive piglets, isolated conduit pulmonary arteries did not relax when stimulated with acetylcholine; they always relaxed to sodium nitroprusside. These data suggest that the first stages of perturbations reported during pulmonary venous hypertension occur at the level of the pulmonary vascular endothelium. This neonatal model of pulmonary hypertension is simple to perform and might be useful for further investigations.
Registry Numbers: 15078-28-1 (Nitroprusside) 51-84-3 (Acetylcholine)
Institutional address: Laboratoire de Chirurgie Experimentale Marie Lannelongue Hospital Le Plessis-Robinson France.
(REFERENCE 14 OF 102) 95209446
Bridges ND Mallory GB Jr Huddleston CB Canter CE Sweet SC Spray TL Lung transplantation in children and young adults with cardiovascular disease.
In: Ann Thorac Surg (1995 Apr) 59(4):813-20; discussion 820-1
ISSN: 0003-4975
Single or bilateral lung transplantation was performed in 20 patients with pulmonary hypertension or an inadequate pulmonary vascular bed; all but 1 had congenital heart disease. The average age was 6.3 years (range, 3 months to 23.9 years). All were in New York Heart Association class IV, and 6 were hospitalized and receiving intensive support before transplantation. Hospital survival was 70% (14/20), with three additional deaths at 7, 11, and 27 months. A prior thoracic operation contributed to three of six hospital deaths from hemorrhage. All late deaths were due directly or indirectly to obliterative bronchiolitis. At a mean follow-up of 19 months (range, 2 to 48 months), 10 of 11 survivors are in New York Heart Association class I. Survival after hospital discharge and incidence of obliterative bronchiolitis are similar in a contemporary group of 41 patients of comparable age who underwent lung transplantation for pulmonary disease (p = not significant). Single or bilateral lung transplantation is an acceptable therapy for children with pulmonary hypertension, congenital heart disease, or both. Further investigation in the areas of pretransplantation survival, operative risk factors, and long-term outcome of single-lung recipients and recipients with hemodynamically insignificant intracardiac lesions are needed to develop optimal decision-making strategies for these patients.
Institutional address: Division of Cardiothoracic Surgery Washington University School of Medicine St. Louis Missouri.
(REFERENCE 15 OF 102) 95209416
de Jong PL Bogers AJ Witsenburg M Bos E Arterial switch for pulmonary venous obstruction complicating Mustard procedure.
In: Ann Thorac Surg (1995 Apr) 59(4):1005-7
ISSN: 0003-4975
Two patients underwent an arterial switch procedure for the relief of severe pulmonary venous obstruction complicating a Mustard procedure. Without preparatory pulmonary banding, both patients had adequate left ventricular function due to secondary pulmonary hypertension. At 8 and 4 years after the procedure, both patients are in New York Heart Association functional class I, with echocardiographic evidence of good left and right ventricular function.
Institutional address: Department of Thoracic Surgery Sophia/Dijkzigt University Hospital Rotterdam The Netherlands.
(REFERENCE 16 OF 102) 95194110
Gorcsan J 3rd Edwards TD Ziady GM Katz WE Griffith BP Transesophageal echocardiography to evaluate patients with severe pulmonary hypertension for lung transplantation.
In: Ann Thorac Surg (1995 Mar) 59(3):717-22
ISSN: 0003-4975
The surgical approach to lung transplantation for patients with severe pulmonary hypertension will be dependent on the primary disease and specific cardiac anatomy. To determine the safety and utility of transesophageal echocardiography in the management of patients with severe pulmonary hypertension who are being evaluated for lung transplantation, we studied 48 consecutive patients, aged 38 +/- 11 years, with pulmonary artery systolic pressure of 70 mm Hg or greater. All patients previously underwent left and right heart catheterization, transthoracic echocardiography, and radionuclide ventriculography. Transesophageal echocardiography was tolerated well by all patients. Additional data that significantly altered surgical therapy was found in 12 of 48 patients (25%): proximal pulmonary artery thrombi (3), patent foramen ovale with significant right to left shunting (2), atrial septal defect (2), double-outlet right ventricle (2), ventricular septal defect (2), and exclusion of atrial septal defect (1). These findings were confirmed surgically in all patients except 3, who died awaiting transplantation. Transesophageal echocardiography is useful in the evaluation of patients with severe pulmonary hypertension.
Institutional address: Division of Cardiology University of Pittsburgh Medical Center Pennsylvania 15261.
(REFERENCE 17 OF 102) 95070433
Bando K Keenan RJ Paradis IL Konishi H Komatsu K Hardesty RL Griffith BP Impact of pulmonary hypertension on outcome after single-lung transplantation.
In: Ann Thorac Surg (1994 Nov) 58(5):1336-42
ISSN: 0003-4975
Single lung transplantation for pulmonary hypertension (PH) remains a controversial therapy. We retrospectively studied 48 consecutive recipients of single-lung allografts to determine if preoperative PH was associated with increased mortality or morbidity. Recipients were divided into two groups; those who did have preoperative PH, defined as mean pulmonary arterial pressure less than or equal to 30 mm Hg (n = 29; group 1), and those recipients with PH who had a mean pulmonary arterial pressure greater than 30 mm Hg (n = 19; group II). Mean pulmonary arterial pressure and pulmonary vascular resistance decreased significantly after transplantation in recipients with PH. These values remained significantly higher as compared with those in recipients without pretransplantation PH. Postoperative pulmonary ventilation/perfusion scans demonstrated significant ventilation/perfusion mismatch in lung allografts with pretransplantation PH (p < 0.05). The mean duration of intensive care unit stay was significantly longer in recipients with PH. Although operative mortality was similar between the groups, preoperative PH was associated with significantly lower 1-year survival (53% versus 72%; p < 0.05) and New York Heart Association functional class (p < 0.05). We conclude that preoperative PH in single-lung transplant recipients is associated with significantly increased mortality, prolonged intensive care unit stay, and less symptomatic improvement. Thus, despite a shortage of donor organs, single-lung transplantation may be suboptimal therapy in patients with PH. Further study comparing single versus bilateral lung transplantation for PH is necessary.
Institutional address: Division of Cardiothoracic Surgery University of Pittsburgh School of Medicine Pennsylvania 15213.
(REFERENCE 18 OF 102) 95031472
Mentzer SJ Aranki SF Reilly JJ DeCamp MM Hartigan P O'Donnell W Sugarbaker DJ Single-lung transplantation in situs inversus.
In: Ann Thorac Surg (1994 Oct) 58(4):1176-8
ISSN: 0003-4975
Situs inversus totalis is a rare anatomic condition characterized by the mirror-imaged arrangement of asymmetric thoracic and abdominal organs. Although associated cardiopulmonary disease is uncommon, end- stage lung disease can develop in patients with situs inversus, necessitating transplantation. In this report, we describe a 30-year- old patient with situs inversus totalis and end-stage pulmonary hypertension who underwent successful orthotopic left lung transplantation.
Institutional address: Department of Surgery Brigham and Women's Hospital Harvard Medical School Boston Massachusetts 02115.
(REFERENCE 19 OF 102) 95031439
Tonz M von Segesser LK Schilling J Luscher TF Noll G Leskosek B Turina MI Treatment of acute pulmonary hypertension with inhaled nitric oxide.
In: Ann Thorac Surg (1994 Oct) 58(4):1031-5
ISSN: 0003-4975
We examined the effectiveness of inhaled nitric oxide (NO) as a selective pulmonary vasodilator in acute pulmonary hypertension in an in vivo canine model with fixed cardiac output. In 5 dogs, total right heart bypass was instituted, and pulmonary hypertension was induced by infusion of the thromboxane analogue U-46619. During U- 46619 infusion, NO was administered at 10 and 40 ppm for 5 minutes followed by breathing of the oxygen mixture without NO. Pump flow was held constant during the experiment. Infusion of the thromboxane analogue resulted in an increase in pulmonary vascular resistance and systemic vascular resistance from 147 +/- 83 to 740 +/- 126 dyne.s.cm- 5 and from 1,720 +/- 113 to 2,407 +/- 232 dyne.s.cm-5, respectively. During inhalation of 10 ppm NO, pulmonary vascular resistance significantly decreased to 613 +/- 55 dyne.s.cm-5 (p < 0.05) and further decreased to 527 +/- 163 dyne.s.cm-5 with 40 ppm NO inhalation (p < 0.05). Systemic vascular resistance did not change during NO treatment (2,300 +/- 70 dyne.s.cm-5 during 40 ppm NO). There was no increase in intrapulmonary shunting or methemoglobin levels during NO inhalation. In this setting, with a constant cardiac output throughout the experiment, NO acted as a selective pulmonary vasodilator without altering systemic vascular resistance. However, induced pulmonary vasoconstriction was only partially reversed by NO inhalation.
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Clinic for Cardiovascular Surgery University Hospital Zurich Switzerland.
(REFERENCE 20 OF 102) 97379575
Aota M Nomoto S Yamaki S Ban T Pulmonary hypertension caused by medial hypertrophy associated with aortic stenosis and preductal coarctation.
In: Ann Thorac Surg (1997 Jul) 64(1):244-7
ISSN: 0003-4975
A 7-month-old female infant with aortic stenosis, preductal coarctation, and pulmonary hypertension underwent operation. Intraoperative lung biopsy revealed marked medial hypertrophy of the pulmonary arterioles. This histopathology is compatible with persistent pulmonary hypertension in the newborn. She is alive about 5 years after the operation, but pulmonary hypertension remains. The pathogenesis is discussed.
Institutional address: Department of Cardiovascular Surgery Faculty of Medicine Kyoto University Japan.
(REFERENCE 21 OF 102) 97349142
Chen EP Bittner HB Davis RD Jr Van Trigt P 3rd Effects of nitric oxide after cardiac transplantation in the setting of recipient pulmonary hypertension.
In: Ann Thorac Surg (1997 Jun) 63(6):1546-55
ISSN: 0003-4975
BACKGROUND: Recipient pulmonary hypertension secondary to chronic congestive heart failure is a significant risk factor for right ventricular failure after cardiac transplantation. In this study, the hemodynamic and inotropic effects of nitric oxide (NO) were examined after bicaval cardiac transplantation in the setting of monocrotaline pyrrole-induced recipient chronic pulmonary hypertension. METHODS: Twenty dogs underwent 10 successfully completed transplantation experiments. Recipients underwent pulmonary artery injection of 3 mg/kg monocrotaline pyrrole 4 months before transplantation. Measurements were taken 1 hour after cessation of cardiopulmonary bypass and after NO inhalation. Pulmonary vascular impedance was calculated using Fourier analysis, and cardiac function was assessed with load-insensitive means (preload recruitable stroke work). RESULTS: At the time of transplantation, the precardiopulmonary bypass levels of pulmonary vascular resistance in recipient animals were significantly greater when compared with donor levels, and were further significantly increased after cardiopulmonary bypass. Three recipients died after transplantation secondary to acute right ventricular failure. In the surviving animals, NO led to significant improvements in pulmonary vascular resistance and vascular impedance, which occurred in association with significant increases in transpulmonary efficiency. No significant changes were observed in right and left ventricular preload recruitable stroke work after NO inhalation. CONCLUSIONS: These data suggest that NO may be an effective means to improve vascular impedance and pulmonary vascular efficiency after cardiac transplantation in the setting of recipient chronic pulmonary hypertension.
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Department of Surgery Duke University Medical Center Durham North Carolina USA. epc2@acpub.duke.edu
(REFERENCE 22 OF 102) 98391208
Vijay P Szekely L Sharp TG Miller A Bando K Brown JW Adrenomedullin in patients at high risk for pulmonary hypertension.
In: Ann Thorac Surg (1998 Aug) 66(2):500-5
ISSN: 0003-4975
BACKGROUND: Adrenomedullin is a newly identified peptide with profound hypotensive effects. We investigated perioperative adrenomedullin levels among patients with congenital heart disease with and without pulmonary hypertension. METHODS: Levels of plasma adrenomedullin, endothelin-1, and nitric oxide metabolites were measured in three groups: (1) low pulmonary flow (n=11); (2) high flow/low pulmonary arterial pressure (less than 60% systemic pressure) (n=9); and (3) high flow/high pressure (n=10). Samples were obtained preoperatively, on and off pump, and 3, 6, and 12 hours after bypass. RESULTS: Adrenomedullin levels were highest in the low pulmonary flow group (189.7+/-15 pg/mL low flow versus 103.1+/-9.5 pg/mL high flow/low pulmonary and 139+/-17.5 pg/mL high flow/high pressure at 12 hours; p < or = 0.05). The arterial pressure/systemic pressure remained significantly lower in the high flow/low pulmonary pressure compared with the high flow/high pressure group (0.37+/-0.08 versus 0.62+/-0.11; p < 0.005). Perioperative endothelin-1 and nitric oxide levels remained low in the low pulmonary flow group but increased progressively in both high flow groups. CONCLUSIONS: Circulating plasma adrenomedullin appears to affect baseline vascular tone in patients with intact endothelial function. It may interact with nitric oxide and endothelin-1 to help regulate blood pressure perioperatively in patients with congenital heart disease.
Registry Numbers: 10102-43-9 (Nitric Oxide) 148498-78-6 (adrenomedullin)
Institutional address: Section of Cardiothoracic Surgery Indiana University School of Medicine Indianapolis 46202-5125 USA. pvijay@iupui.edu
(REFERENCE 23 OF 102) 98309312
Katsumata T Shinfeld A Westaby S Temporary aorto-pulmonary shunt for pulmonary hypertension after truncus arteriosus repair.
In: Ann Thorac Surg (1998 Jun) 65(6):1764-5
ISSN: 0003-4975
We describe successful management of pulmonary hypertension with a reversible aorto-pulmonary (central) shunt and inhaled nitric oxide gas after truncus arteriosus repair. A temporary central shunt may provide a lifeline in those cases refractory to pharmacologic pulmonary vasodilation as long as marginal systemic oxygenation can be maintained.
Registry Numbers: 10102-43-9 (Nitric Oxide) 7782-44-7 (Oxygen)
Institutional address: Department of Cardiac Surgery Oxford Heart Centre John Radcliffe Hospital England.
(REFERENCE 24 OF 102) 98186453
Wekerle T Klepetko W Taghavi S Birsan T Lung transplantation for primary pulmonary hypertension and giant pulmonary artery aneurysm.
In: Ann Thorac Surg (1998 Mar) 65(3):825-7
ISSN: 0003-4975
We report the case of an 18-year-old patient with a giant pulmonary artery aneurysm and primary pulmonary hypertension who was successfully treated with bilateral lung transplantation and complete reconstruction of the pulmonary artery.
Institutional address: Department of Cardiothoracic Surgery University of Vienna Vienna General Hospital Austria.
(REFERENCE 25 OF 102) 98143768
Argenziano M Choudhri AF Moazami N Rose EA Smith CR Levin HR Smerling AJ Oz MC Randomized, double-blind trial of inhaled nitric oxide in LVAD recipients with pulmonary hypertension [see comments]
In: Ann Thorac Surg (1998 Feb) 65(2):340-5
ISSN: 0003-4975
BACKGROUND: Pulmonary vascular resistance is often elevated in patients with congestive heart failure, and in those undergoing left ventricular assist device (LVAD) insertion, it may precipitate right ventricular failure and hemodynamic collapse. Because the effectiveness of inotropic and vasodilatory agents is limited by systemic effects, right ventricular assist devices are often required. Inhaled nitric oxide (NO) is an effective, specific pulmonary vasodilator that has been used successfully in the management of pulmonary hypertension. METHODS: Eleven of 23 patients undergoing LVAD insertion met criteria for elevated pulmonary vascular resistance on weaning from cardiopulmonary bypass (mean pulmonary artery pressure > 25 mm Hg and LVAD flow rate < 2.5 L x min[-1] x m[-2]) and were randomized to receive either inhaled NO at 20 ppm (n = 6) or nitrogen (n = 5). Patients not manifesting a clinical response after 15 minutes were given the alternative agent. RESULTS: Hemodynamics for the group at randomization were as follows: mean arterial pressure, 72 +/- 6 mm Hg; mean pulmonary artery pressure, 32 +/- 4 mm Hg; and LVAD flow, 2.0 +/- 0.3 L x min(-1) x m(- 2). Patients receiving inhaled NO exhibited significant reductions in mean pulmonary artery pressure and increases in LVAD flow, whereas none of the patients receiving nitrogen showed hemodynamic improvement. Further, when the nitrogen group was subsequently given inhaled NO, significant hemodynamic improvements ensued. There were no significant changes in mean arterial pressure in either group. CONCLUSIONS: Inhaled NO induces significant reductions in mean pulmonary artery pressure and increases in LVAD flow in LVAD recipients with elevated pulmonary vascular resistance. We conclude that inhaled NO is a useful intraoperative adjunct in patients undergoing LVAD insertion in whom pulmonary hypertension limits device filling and output.
Comment in: Ann Thorac Surg 1998 Nov;66(5):1862-3
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Department of Surgery Columbia University College of Physicians and Surgeons New York New York USA. ma66@columbia.edu
(REFERENCE 26 OF 102) 96378460
Fullerton DA Jaggers J Jones SD Brown JM McIntyre RC Jr Adenosine for refractory pulmonary hypertension.
In: Ann Thorac Surg (1996 Sep) 62(3):874-7
ISSN: 0003-4975
We report 2 patients with refractory acute pulmonary hypertension. In both, a central venous infusion of adenosine into the circulation effectively lowered pulmonary arterial pressure when standard treatment measures had failed, and reversed the clinical state of shock by achieving pulmonary vasodilatation. We conclude that adenosine may help lower pulmonary arterial pressure without lowering systemic arterial pressure in the setting of acute pulmonary hypertension when standard measures have failed.
Registry Numbers: 58-61-7 (Adenosine)
Institutional address: Department of Surgery University of Colorado Health Sciences Center Denver 80262 USA.
(REFERENCE 27 OF 102) 96378439
Goldman AP Delius RE Deanfield JE de Leval MR Sigston PE Macrae DJ Nitric oxide might reduce the need for extracorporeal support in children with critical postoperative pulmonary hypertension.
In: Ann Thorac Surg (1996 Sep) 62(3):750-5
ISSN: 0003-4975
BACKGROUND: Postoperative pulmonary hypertension is a life- threatening, yet reversible complication of congenital heart operations. Although inhaled nitric oxide (iNO), a selective pulmonary vasodilator, has been shown extensively to improve short- term oxygenation and hemodynamic indices in these patients, its influence on patient outcome has not been evaluated. The purpose of this study was to assess retrospectively whether patients who fulfilled our criteria for extracorporeal life support (ECLS) for critical postoperative pulmonary hypertension still required ECLS after the administration of iNO therapy. METHODS: Since January 1992, 10 patients (age 3 days to 10 months) fulfilled the criteria at our institution for ECLS for postoperative pulmonary hypertension. Of these, 5 could not be separated from cardiopulmonary bypass because of pulmonary hypertension, and 5 had critical pulmonary hypertension (pulmonary arterial pressure approaching systemic arterial pressure) causing severe cardiopulmonary compromise. RESULTS: Six of the 10 ECLS candidates had a sustained response to iNO and survived to discharge from the hospital, without the need for rescue ECLS. Three patients still required ECLS after 30 minutes, 4 hours, and 8 hours of beginning iNO because of failing cardiac output, and 2 survived. The remaining patient died after 5 days of iNO therapy, but was no longer a candidate for ECLS because of sepsis and multiorgan system failure. CONCLUSIONS: Children with critical pulmonary hypertension unresponsive to maximal conventional treatment may be managed successfully with iNO without the need for rescue ECLS. A trial of iNO should therefore be given before the use of ECLS in these patients.
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Cardiothoracic Unit Great Ormond Street Hospital for Children London United Kingdom.
(REFERENCE 28 OF 102) 96225256
Mayer E Dahm M Hake U Schmid FX Pitton M Kupferwasser I Iversen S Oelert H Mid-term results of pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension.
In: Ann Thorac Surg (1996 Jun) 61(6):1788-92
ISSN: 0003-4975
BACKGROUND. In patients with chronic thromboembolic pulmonary hypertension, acute and striking decreases of pulmonary artery pressures and vascular resistance can be achieved by pulmonary thromboendarterectomy. In this study, the long-term effects of pulmonary thromboendarterectomy on hemodynamic indices and right ventricular function were investigated. METHODS. Sixty-five patients (31 women and 34 men; mean age, 47 +/- 17 years; range, 19 to 69 years; New York Heart Association [NYHA] functional class II, n = 3; class III, n = 38; class IV, n = 24) were reassessed 13 to 48 months (mean, 27 months) after pulmonary thromboendarterectomy. Measurements are reported as mean +/- standard deviation. RESULTS. All patients reported a significant improvement of symptoms: 46 patients were in NYHA functional class I, 16 patients in class II, and 3 patients in class III. Mean pulmonary vascular resistance was significantly reduced compared with preoperative and postoperative values (preoperative: 1,015 +/- 454 dynes.s.cm-5; postoperative: 322 +/- 154 dynes.s.cm-5; follow-up: 198 +/- 72 dynes.s.cm-5; p < 0.001 versus preoperative; p < 0.025 versus postoperative). Concomitantly, cardiac index was significantly increased compared with preoperative values (preoperative: 2.0 +/- 0.7 L.min-1.m-2; follow-up: 2.9 +/- 0.5 L.min- 1.m-2; p < 0.001). Significant reductions of right ventricular dimensions and recovery of right ventricular function could be demonstrated radiologically and echocardiographically. In 3 patients (preoperative NYHA class IV, NYHA class III at follow-up) with proven coagulation abnormalities, pulmonary vascular resistance was moderately increased at follow-up compared with postoperative measurements. CONCLUSIONS. In patients with chronic thromboembolic pulmonary hypertension, a persistent decrease of pulmonary vascular resistance and improvement of right ventricular function and NYHA functional status can be achieved by pulmonary thromboendarterectomy.
Institutional address: Department for Cardiothoracic Johannes Gutenberg-University Hospital Mainz Germany.
(REFERENCE 29 OF 102) 96201801
Aris A Camara ML As originally published in 1988: Long-term results of mitral valve surgery in patients with severe pulmonary hypertension. Updated in 1996.
In: Ann Thorac Surg (1996 May) 61(5):1583-4
ISSN: 0003-4975
Mitral valve surgery was performed in 88 patients with severe pulmonary hypertension (average systolic pulmonary artery pressure, 94.7 +/- 22 mm Hg; range, 70-180 mm Hg) over a 10-year period. Sixty- four patients (73%) were in New York Heart Association Functional Class III or IV. There were 64 valve replacements and 24 open mitral commissurotomies. Operative mortality was 5.6% (5 patients) and was not related to the degree of pulmonary hypertension, surgical procedure performed, or type of valve lesion. A 100% follow-up was obtained, ranging from nine months to 10 years, with a mean of 44 months. Six late cardiac deaths (7.2%) occurred, 5 in patients with valve replacement and 1 in a patient who underwent a commissurotomy. Actuarial survival was 86 +/- 3% at five years and 83 +/- 4% at 10 years. Fourteen patients underwent right ventricular catheterization a mean of 24 months following operation. Systolic pulmonary artery pressure had decreased from a mean preoperative value of 101 +/- 22 to 40.5 +/- 7 mm Hg (p < 0.001). Cardiac index increased by 55% of the preoperative values. Functional status improved markedly; 71 survivors (93%) were in New York Heart Association Class I or II. These results indicate that, in patients with mitral valve lesions and severe pulmonary hypertension, (1) surgical procedures can be performed with an acceptable operative mortality; (2) excellent long- term survival and functional results can be obtained; and (3) pulmonary hypertension decreases significantly after operation. Patients with mitral valve disease may benefit from surgical treatment regardless of the degree of pulmonary hypertension.
Institutional address: Cardiac Surgery Service Hospital de la Santa Creu i Sant Pau Barcelona Spain.
(REFERENCE 30 OF 102) 96186312
Luciani GB Chang AC Starnes VA Surgical repair of transposition of the great arteries in neonates with persistent pulmonary hypertension.
In: Ann Thorac Surg (1996 Mar) 61(3):800-5
ISSN: 0003-4975
BACKGROUND: Pulmonary hypertension due to persistent fetal circulation is rarely associated with transposition of the great arteries and intact ventricular septum. Previous attempts at management of affected neonates using prostaglandin E1 and balloon atrial septotomy followed by surgical repair have been largely unsuccessful. METHODS: Between September 1992 and April 1995, 45 neonates underwent repair of transposition of the great arteries with the arterial switch operation. Two patients (4%) with transposition of the great arteries and intact ventricular septum presented with profound reversed differential desaturation and right-to-left shunting at the level of the ductus arteriosus after balloon atrial septotomy. A diagnosis of persistent pulmonary hypertension was established and both neonates entered an experimental management protocol using inhaled nitric oxide and rapid arterial switch operation. RESULTS: Preoperative hemodynamic stabilization was achieved in 1 patient using 40 parts per million of inhaled nitric oxide, whereas the other required in addition extracorporeal membrane oxygenation for severe biventricular dysfunction. Both underwent successful surgical repair 4 to 5 days after admission, but received postoperatively 1 week of inhaled nitric oxide therapy for persistent pulmonary hypertension. Follow-up echocardiography at 3 months showed good biventricular function and normal geometry of the ventricular septum, suggesting low pulmonary artery pressure, in both. CONCLUSIONS: A management protocol using inhaled nitric oxide and extracorporeal membrane oxygenation followed by the arterial switch operation was successfully used in neonates with transposition of the great arteries, intact ventricular septum, and persistent pulmonary hypertension. Wider use of preoperative and postoperative inhaled nitric oxide may improve the surgical outcome of this difficult subset of patients.
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Division of Cardiothoracic Surgery Children's Hospital Los Angeles California USA.
(REFERENCE 31 OF 102) 96182196
Fullerton DA Jones SD Grover FL McIntyre RC Jr Adenosine effectively controls pulmonary hypertension after cardiac operations [see comments]
In: Ann Thorac Surg (1996 Apr) 61(4):1118-23; discussion 1123-4
ISSN: 0003-4975
BACKGROUND: Pulmonary hypertension secondary to increased pulmonary vascular resistance may greatly complicate the perioperative management of patients having cardiac operations. Adenosine may have a therapeutic role as a selective pulmonary vasodilator. The purpose of this study was to examine the pulmonary hemodynamic effects of a central venous infusion of adenosine in cardiac operative patients with pulmonary hypertension. METHODS: Ten cardiac patients with pulmonary hypertension (age, 62 +/- 6 years) were studied in the operating room under general anesthesia after weaning from cardiopulmonary bypass. Cardiac output, pulmonary vascular resistance, systemic vascular resistance, mean pulmonary arterial pressure, and mean systemic arterial pressure were determined before, during, and after central venous infusion of adenosine (50 micrograms x kg-1 x min -1) for 15 minutes. Statistical analysis was by analysis of variance, and significance was accepted at p < 0.05. RESULTS: Adenosine produced significant pulmonary vasodilation. Mean pulmonary arterial pressure was lowered from 36 +/- 1 to 28 +/- 2 mm Hg (p < 0.05), and pulmonary vascular resistance was lowered from 560 +/- 30 to 260 +/- 30 dynes x s x cm-5 (p < 0.05) during adenosine administration. At the same time, cardiac output rose from 4.0 +/- 0.6 to 6.2 L/min (p < 0.05). Pulmonary vascular resistance, mean pulmonary arterial pressure, and cardiac output returned to baseline after the adenosine infusion was stopped. There was no change in systemic mean arterial pressure during adenosine infusion. CONCLUSIONS: Adenosine may be used clinically as a selective pulmonary vasodilating agent to optimize pulmonary hemodynamic indices without adverse systemic hemodynamic effects in patients with pulmonary hypertension having cardiac operations. It may be particularly valuable in patients with right heart dysfunction by selectively lowering right ventricular afterload.
Comment in: Ann Thorac Surg 1996 Apr;61(4):1051-2
Registry Numbers: 58-61-7 (Adenosine)
Institutional address: Department of Surgery University of Colorado Health Sciences Center Denver 80262 USA.
(REFERENCE 32 OF 102) 96160232
Fullerton DA McIntyre RC Jr Kirson LE St. Cyr JA Whitman GJ Grover FL Impact of respiratory acid-base status in patients with pulmonary hypertension.
In: Ann Thorac Surg (1996 Feb) 61(2):696-701
ISSN: 0003-4975
BACKGROUND. The perioperative management of patients undergoing mitral valve replacement (MVR) with pulmonary hypertension from mitral stenosis may be complicated by increased pulmonary vascular resistance. The purpose of this study was to examine the influence of respiratory acid-base status on the pulmonary hemodynamic indices of patients with pulmonary hypertension before and after MVR. METHODS. Ten patients with pulmonary hypertension from mitral stenosis (mean preoperative systolic pulmonary artery pressure, 73 +/- 8 mm Hg) undergoing MVR were studied in the operating room before and after MVR. Arterial partial pressure of carbon dioxide was manipulated by the addition of 5% carbon dioxide to the breathing circuit. Hemodynamic data were collected as the partial pressure of carbon dioxide rose from 30 mm Hg to 50 mm Hg and decreased back to 30 mm Hg. RESULTS. There were no differences in mean pulmonary artery pressure or pulmonary vascular resistance before and after MVR. Before MVR, mean pulmonary artery pressure increased from 32 +/- 1 mm Hg to 48 +/- 1 mm Hg as the partial pressure of carbon dioxide rose from 30 mm Hg to 50 mm Hg (p < 0.05), and pulmonary vascular resistance rose from 379 +/- 30 to 735 +/- 40 dynes.second.cm-5 (p < 0.05). These effects on mean pulmonary artery pressure and pulmonary vascular resistance were not different after MVR. CONCLUSION. Respiratory acid-base status has a profound impact upon pulmonary vascular resistance in patients with pulmonary hypertension from mitral stenosis undergoing MVR. This impact persists in the immediate postoperative period. We conclude that respiratory acidemia should be avoided in these patients, whereas respiratory alkalemia may be used to help minimize pulmonary vascular resistance.
Institutional address: Department of Surgery University of Colorado Denver USA.
(REFERENCE 33 OF 102) 96146333
Pinelli G Mertes PM Carteaux JP Hubert T Dopff C Burtin P Villemot JP Inhaled nitric oxide as an adjunct to pulmonary thromboendarterectomy.
In: Ann Thorac Surg (1996 Jan) 61(1):227-9
ISSN: 0003-4975
In chronic pulmonary vascular thrombotic disease, pulmonary thromboendarterectomy has proved to be effective in reducing pulmonary hypertension and improving gas exchange. However, persistent pulmonary hypertension and unrelenting reperfusion edema are the main causes of death. We report a case of pulmonary thromboendarterectomy followed by an immediate unfavorable postoperative course with acute and persistent pulmonary hypertension, gas exchange impairment, and heart dysfunction. In this particular case, inhaled nitric oxide was successfully administered.
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Service de Chirurgie Cardiaque et Transplantations Centre Hospitalo-Universitaire de Nancy France.
(REFERENCE 34 OF 102) 96110241
Shah AS Smerling AJ Quaegebeur JM Michler RE Nitric oxide treatment for pulmonary hypertension after neonatal cardiac operation.
In: Ann Thorac Surg (1995 Dec) 60(6):1791-3
ISSN: 0003-4975
This report describes a newborn with transposition of the great arteries who underwent a Blalock-Taussig shunt with transient improvement in oxygenation, but required emergent insertion of a central shunt later the same day due to progressive hypoxia and cardiac arrest. Two hours after central shunt insertion, sudden episodes of hypoxia and hypotension developed that were resistant to all pharmacologic therapy. Inhaled nitric oxide (25 ppm) was then administered with dramatic improvement in oxygenation and hemodynamics within minutes. The patient's condition stabilized after these measures, and nitric oxide therapy was discontinued after 2 days.
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Division of Cardiothoracic Surgery College of Physicians and Surgeons Columbia University New York New York USA.
(REFERENCE 35 OF 102) 96064509
Zhou Q Lai Y Wei H Song R Wu Y Zhang H Unidirectional valve patch for repair of cardiac septal defects with pulmonary hypertension [see comments]
In: Ann Thorac Surg (1995 Nov) 60(5):1245-8; discussion 1249
ISSN: 0003-4975
BACKGROUND. Congenital septal defects with a large left-to-right shunt often cause pulmonary hypertension, which complicates surgical repair of the defects. METHODS. Twenty-four patients with congenital cardiac septal defects and severe pulmonary hypertension had operation to close the septal defect using a unidirectional valve patch during a 3-year period. The ratio of systolic pulmonary artery pressure to systolic arterial blood pressure was near to or more than 1.0 in all patients. RESULTS. Two patients died in the hospital after operation, and there have been no deaths during intermediate term follow-up. Mean pulmonary artery pressure decreased from 80 +/- 12 mm Hg to 56 +/- 18 mm Hg. The ratio of pulmonary artery pressure to systemic arterial pressure dropped from 1.1 +/- 0.1 mm Hg to 0.7 +/- 0.1 mm Hg. The unidirectional valve patch functioned allowing right to left shunting in 4 patients with a systolic pulmonary artery pressure more than systolic arterial blood pressure immediately after closure of a septal defect. The patch sealed or was effectively closed by the third postoperative day. There was impressive improvement in symptoms and exercise tolerance after operation during the 3-month to 3-year (mean, 1.1 year) follow-up period. CONCLUSIONS. The unidirectional valve patch is useful for management of patients having operation to close cardiac septal defects in the presence of severe pulmonary hypertension.
Comment in: Ann Thorac Surg 1996 Aug;62(2):626-8
Institutional address: Department of Cardiac Surgery Beijing Heart Lung and Blood Vessel Medical Center People's Republic of China.
(REFERENCE 36 OF 102) 97116295
Atz AM Adatia I Wessel DL Rebound pulmonary hypertension after inhalation of nitric oxide.
In: Ann Thorac Surg (1996 Dec) 62(6):1759-64
ISSN: 0003-4975
BACKGROUND: We describe the hemodynamic response to initiation and withdrawal of inhaled nitric oxide (NO) in infants with pulmonary hypertension after surgical repair of total anomalous pulmonary venous connection. METHODS: Between January 1, 1992, and January 1, 1995, 20 patients underwent repair of total anomalous pulmonary venous connection. Nine patients had postoperative pulmonary hypertension and received a 15-minute trial of inhaled NO at 80 parts per million. Five of these patients received prolonged treatment with NO at 20 parts per million or less. RESULTS: Mean pulmonary artery pressure decreased from 35.6 +/- 2.4 to 23.7 +/- 2.0 mm Hg (mean +/- standard error of the mean) (p = 0.008), and pulmonary vascular resistance decreased from 11.5 +/- 2.0 to 6.4 +/- 1.0 U.m2 (p = 0.03). After prolonged treatment with NO, pulmonary artery pressure increased transiently in all patients when NO was discontinued. CONCLUSIONS: After operative repair of total anomalous pulmonary venous connection, inhaled NO selectively vasodilated all patients with pulmonary hypertension. Withdrawal of NO after prolonged inhalation was associated with transient rebound pulmonary hypertension that dissipated within 60 minutes. Appreciation of rebound pulmonary hypertension may have important implications for patients with pulmonary hypertensive disorders when interruption of NO inhalation is necessary or when withdrawal of NO is planned.
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Cardiac Intensive Care Unit Children's Hospital Boston Massachusetts 02115 USA.
(REFERENCE 37 OF 102) 94280228
Lupinetti FM Bolling SF Bove EL Brunsting LA 3rd Crowley DC Lynch JP Orringer MB Whyte RI Deeb GM Selective lung or heart-lung transplantation for pulmonary hypertension associated with congenital cardiac anomalies.
In: Ann Thorac Surg (1994 Jun) 57(6):1545-8; discussio 1549
ISSN: 0003-4975
Fixed pulmonary hypertension has been a contraindication to correction of congenital heart defects. Beginning in February 1991, we pursued a policy of performing single-lung transplantation with intracardiac repair for selected patients with this physiology, reserving heart-lung transplantation for those with unreconstructable heart disease. Of 7 patients treated under this protocol, 5 underwent single-lung transplantation and intracardiac repair. The cardiac anomalies included complete atrioventricular canal (1), aortopulmonary window (1), atrial septal defect (1), and ventricular septal defect (2). One patient died perioperatively. All 4 patients surviving operation remained alive through the first postoperative year, but 3 died 13, 17, and 22 months after operation. Two other patients with pulmonary hypertension (1 with tricuspid atresia, 1 after failed Mustard procedure) received a heart-lung transplant and are well 15 and 18 months after operation. This experience demonstrates that selected patients with major intracardiac defects and pulmonary hypertension may have good early results after cardiac repair and single-lung transplantation, but that long-term results are considerably less favorable.
Institutional address: Department of Surgery University of Michigan School of Medicine Ann Arbor.
(REFERENCE 38 OF 102) 94234809
Adatia I Lillehei C Arnold JH Thompson JE Palazzo R Fackler JC Wessel DL Inhaled nitric oxide in the treatment of postoperative graft dysfunction after lung transplantation.
In: Ann Thorac Surg (1994 May) 57(5):1311-8
ISSN: 0003-4975
Pulmonary hypertension and transient graft dysfunction may complicate the postoperative course of patients undergoing lung transplantation. We report the acute effect of inhaled nitric oxide (80 ppm) on hemodynamics and gas exchange in 6 patients (median age, 14 years; range, 5 to 21 years) after lung transplantation as well as the effect of extended treatment over 40 to 69 hours in 2 patients. In 5 patients with pulmonary hypertension nitric oxide lowered mean pulmonary artery pressure (from 38.4 +/- 1.6 to 29.4 +/- 3.1 mm Hg; p < 0.05), pulmonary vascular resistance index (from 9.3 +/- 1.4 to 6.4 +/- 1.3 Um2; p < 0.05), and intrapulmonary shunt fraction (from 28.6% +/- 8.3% to 21.0% +/- 5.7%; p < 0.05). There was a 28.4% +/- 7.2% reduction in transpulmonary pressure gradient with only minor accompanying effects on the systemic circulation. Mean arterial pressure decreased only 2.7% +/- 5% (from 76.4 +/- 2.2 to 74 +/- 2.3 mm Hg; p = not significant), and systemic vascular resistance index by 4.2% +/- 9.7% (from 21.7 +/- 3.1 to 20.6 +/- 3.6 Um2; p = not significant). Cardiac index was unchanged (from 3.5 +/- 0.8 to 3.6 +/- 0.7 L.min-1.m-2; p = not significant). Nitric oxide caused a sustained improvement in oxygenation and pulmonary artery pressure during extended therapy at doses of 10 ppm. There were no major side effects. However, transient methemoglobinemia (9%) developed in 1 patient after 10 hours of nitric oxide treatment. Nitric oxide may be useful in the treatment of pulmonary hypertension and the impaired gas exchange that occurs after lung transplantation.
Registry Numbers: 10102-43-9 (Nitric Oxide) 10102-44-0 (Nitrogen Dioxide) 51-84-3 (Acetylcholine) 9008-37-1 (Methemoglobin)
Institutional address: Department of Cardiology Children's Hospital Boston Massachusetts 02115.
(REFERENCE 39 OF 102) 94107022
Komai H Yamamoto F Tanaka K Yagihara T Kawashima Y Prevention of lung injury during open heart operations for congenital heart defects.
In: Ann Thorac Surg (1994 Jan) 57(1):134-40
ISSN: 0003-4975
To elucidate free radical-induced lung injury associated with open heart operations for congenital heart defects, we studied 23 such patients. Maximum plasma chemiluminescence level (a marker of peroxylipids) in patients with pulmonary hypertension (n = 8) was higher than in patients with cyanotic disease (n = 8) (1,115.4 +/- 189.9 versus 728.8 +/- 48.3 counts; p < 0.05). There was a significant correlation between the maximum chemiluminescence level and preoperative pulmonary to systemic arterial pressure ratio (r = 0.929; p < 0.05). To investigate the effect of allogeneic leukocytes, we compared pulmonary hypertensive patients without allogeneic leukocyte transfusion during operation (n = 7) with the group with pulmonary hypertension. Both maximum chemiluminescence level during bypass (712.4 +/- 24.9 versus 1,115.4 +/- 189.9 counts; p < 0.05) and percent decrease in pulmonary arterial pressure after bypass (44.7% +/- 6.2% versus 28.2% +/- 4.5%; p < 0.05) were significantly improved, suggesting that depletion of leukocytes decreased the lung injury induced by free radical reaction.
Institutional address: Department of Cardiovascular Surgery National Cardiovascular Center Osaka Japan.
(REFERENCE 40 OF 102) 93263719
Komai H Yamamoto F Tanaka K Murashita T Shibata T Sakai H Kawashima Y Increased lung injury in pulmonary hypertensive patients during open heart operations.
In: Ann Thorac Surg (1993 May) 55(5):1147-52
ISSN: 0003-4975
To investigate lung injury in adult open heart operations during extracorporeal circulation, we measured plasma chemiluminescence levels. Nineteen patients were divided into two groups depending on preoperative pulmonary artery pressure: a pulmonary hypertension group (n = 11) and a control group (n = 8). Plasma samples were taken simultaneously from arterial and central venous lines at six different points during and early after operation. Arteriovenous difference of chemiluminescence (counts/10 seconds) increased significantly only in the pulmonary hypertension group (from -19.1 +/- 8.3 at the end of cross-clamping to 23.7 +/- 12.4 at the end of bypass; p < 0.01). There was a positive correlation between peak values of arterial plasma chemiluminescence and postoperative respiratory index in the pulmonary hypertension group (p < 0.05). In addition, during the first 12 hours postoperatively, arteriovenous difference of chemiluminescence in the pulmonary hypertension group changed significantly from negative to positive values (p < 0.05). These data suggest that free radical activity (detected by chemiluminescence) was deeply involved in lung injury during and also early after open heart operations, especially in pulmonary hypertensive patients.
Registry Numbers: 124-38-9 (Carbon Dioxide) 7782-44-7 (Oxygen)
Institutional address: Department of Cardiovascular Surgery and Clinical Laboratory National Cardiovascular Center Osaka Japan.
(REFERENCE 41 OF 102) 93159212
Chang H Wu GJ Wang SM Hung CR Plasma endothelin levels and surgically correctable pulmonary hypertension.
In: Ann Thorac Surg (1993 Feb) 55(2):450-8
ISSN: 0003-4975
To know the changes in plasma endothelin of patients with pulmonary hypertension, we studied 32 patients with valvular heart disease. Among them, 22 patients had pulmonary hypertension (group I) and 10 had pulmonary arterial pressures in the normal range (group II). Plasma endothelin-1 concentrations of the patients in group I were significantly greater than those of the patients in group II (p < 0.05). No significant difference in plasma endothelin-3 concentrations existed between the two groups. Cardiac output and pulmonary capillary wedge pressure had a linear correlation with plasma endothelin-1 levels. There was also a significant correlation between plasma endothelin-1 levels and hemodynamic indicators of severity of pulmonary hypertension, such as mean pulmonary arterial pressure and pulmonary vascular resistance (p < 0.05). All patients in this study underwent surgical procedures for the correction of valvular lesions. All patients in group I showed a decrease in pulmonary arterial pressures, and their plasma endothelin-1 levels decreased from 3.84 +/- 0.20 pg/mL to 1.66 +/- 0.07 pg/mL (p < 0.05), whereas the plasma endothelin-3 levels had only slight variation from 0.64 +/- 0.11 pg/mL to 0.75 +/- 0.06 pg/mL (p > 0.05) between the preoperative and the postoperative stages. The results demonstrated that plasma endothelin-1 rather than endothelin-3 had a role in pulmonary hypertension. Several pieces of evidence pointed out that endothelin-1 functioned as a reactive mediator during vasoconstriction in the case of pulmonary hypertension rather than as a triggering factor of pulmonary hypertension.
Institutional address: Department of Emergency Medicine National Taiwan University Hospital Taipei Republic of China.
(REFERENCE 42 OF 102) 93111831
Yoshida Y Iwaki Y Pham S Dauber JH Yousem SA Zeevi A Morita S Griffith BP Benefits of posttransplantation monitoring of interleukin 6 in lung transplantation.
In: Ann Thorac Surg (1993 Jan) 55(1):89-93
ISSN: 0003-4975
To determine the predictive diagnostic value of interleukin 6 (IL-6) monitoring in lung and heart-lung transplants, we measured posttransplantation serum IL-6 levels in 17 adult lung or heart-lung transplant recipients. Posttransplantation IL-6 elevation patterns were classified into 4 groups: serum IL-6 level remained negative throughout the monitoring period (group 1; n = 1; 6%); several sharp spikes with normal baseline (group 2; n = 9; 53%); persistently high level of serum IL-6 (group 3; n = 3; 18%); and several sharp spikes of serum IL-6 elevation with abnormally high baseline (group 4; n = 4; 24%). One patient without an elevation of IL-6 (group 1) did not experience any episodes of rejection or infection. Nine patients in group 2 had 19 IL-6 spikes, 13 of which were associated with histopathologically or clinically diagnosed rejection, 3 with acute bronchitis, and 1 with diffuse alveolar damage. Three patients in group 3 had persistent infections including cytomegalovirus infection, toxic megacolon, and repeated bacterial infection during the monitoring period, and 4 in group 4 died within 3 months after transplantation. From this study it appears that a spiked elevation of IL-6 could have a predictive value in diagnosing rejection, and persistently high levels of IL-6 indicate the presence of infection. Thus, IL-6 monitoring is beneficial for lung transplant recipients.
Institutional address: Department of Pathology University of Pittsburgh School of Medicine Pennsylvania.
*****CIRCULATION*****
(REFERENCE 43 OF 102) 98045889
Bando K Vijayaraghavan P Turrentine MW Sharp TG Ensing GJ Sekine Y Szekely L Morelock RJ Brown JW Dynamic changes of endothelin-1, nitric oxide, and cyclic GMP in patients with congenital heart disease.
In: Circulation (1997 Nov 4) 96(9 Suppl):II-346-51
ISSN: 0009-7322
BACKGROUND: Pulmonary hypertension causes major morbidity and mortality after congenital heart surgery, but its mechanism remains unclear. METHODS AND RESULTS: Plasma endothelin-1 (ET-1), nitric oxide (NO), and cyclic GMP (cGMP) were assayed at 6 intervals in 50 children undergoing cardiopulmonary bypass (CPB): before CPB, 10 minutes into CPB, and 0, 3, 6, and 12 hours after CPB. Three groups based on pulmonary flow and pressure were analyzed: low flow (LF, n=21), high flow/low pressure (systolic pulmonary pressure/systemic pressure ratio, Pp/Ps<50%, HF-LP, n=11), and high flow/high pressure (Pp/Ps> or =50%, HF-HP, n=19). HF-HP and HF-LP received alpha- blockers (chlorpromazine and/or prazosin). HF-HP patients received nitric oxide donors (nitroglycerin/sodium nitroprusside). ET-1 peaked at 6 hours, with its highest level in the HF-HP group (P<.01, by ANOVA). ET-1 correlated significantly with Pp/Ps at 6 hours (r2=.43, P<.005). In the HF-HP group, ET-1 remained above the other groups at 12 hours (12.7+/-2.5 pg/mL versus 6.4+/-1.1 pg/mL versus 6.5+/-3.8 pg/mL P<.05 by ANOVA). NO metabolites were elevated equivalently for the HF-HP and HF-LP groups (5.7+/-2.6 micromol/L versus 0.3.5+/-2.5 micromol/L at 12 hours, P=NS) despite nitric oxide donors and the excess ET-1 in HF-HP patients. Levels of cGMP were similarly elevated in HF-HP and HF-LP patients during this study. CONCLUSIONS: Endogenous NO may decrease vascular tone and maintain low pulmonary pressure in HF-LP patients. High levels of ET-1, inadequate NO production, and/or impaired responses to NO may increase pulmonary pressure in HF-HP patients.
Registry Numbers: 10102-43-9 (Nitric Oxide) 7665-99-8 (Cyclic GMP)
Institutional address: Section of Cardiothoracic Surgery James W. Riley Hospital for Children and Indiana University Medical Center Indianapolis 46202-5123 USA. kbando@wpo.iupui.edu
(REFERENCE 44 OF 102) 98045856
Chen EP Bittner HB Davis RD Van Trigt P Right ventricular adaptation to increased afterload after orthotopic cardiac transplantation in the setting of recipient chronic pulmonary hypertension.
In: Circulation (1997 Nov 4) 96(9 Suppl):II-141-7
ISSN: 0009-7322
BACKGROUND: Right ventricular (RV) failure remains an important risk factor for early morbidity and mortality after orthotopic cardiac transplantation and is most commonly related to preexistent chronic pulmonary hypertension (CPH) in the recipient, which occurs secondary to long-standing congestive heart failure. This study was designed to assess the compensatory mechanisms of the acutely transplanted RV in the setting of recipient CPH using a canine model of bicaval cardiac transplantation (TX) and monocrotaline pyrrole (MCTP)-induced CPH. METHODS AND RESULTS: Twenty adult mongrel dogs were used for 10 successfully completed TX experiments. Recipients received an injection of 3 mg/kg MCTP 4 months before TX. RV function was assessed with load-insensitive means (preload recruitable stroke work), and Fourier analysis was used to calculate RV hydraulic power and transpulmonary efficiency. At the time of TX, significant increases in the mean pulmonary artery pressure, mean right ventricular pressure, and pulmonary vascular resistance were observed in recipients compared with donors and were further significantly increased after cardiopulmonary bypass. Significant increases in RV preload recruitable stroke work and RV hydraulic power were observed after TX compared with before TX and occurred in association with significant decreases in transpulmonary efficiency. CONCLUSIONS: Significant increases in pulmonary hemodynamic indexes occurred after MCTP injection and were further significantly increased after cardiopulmonary bypass. In the setting of recipient CPH, RV performance adapts acutely after bicaval TX with significant increases in power and contractility. However, a significant decrease in transpulmonary efficiency was also observed, which may improve over time as the RV adapts to the increased afterload.
Institutional address: Department of Surgery Duke University Medical Center Durham NC USA. epchen@itsa.ucsf.edu
(REFERENCE 45 OF 102) 98045904
Friedman R Mears JG Barst RJ Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in primary pulmonary hypertension.
In: Circulation (1997 Nov 4) 96(9):2782-4
ISSN: 0009-7322
BACKGROUND: Primary pulmonary hypertension (PPH) is characterized by vascular injury of pulmonary arterioles, in which endothelial dysfunction may play a major role. Although continuous infusion of prostacyclin (prostaglandin I2, a potent vasodilator released by vascular endothelial cells) improves the clinical status and survival in PPH, its mechanism or mechanisms of action remain unclear. METHODS AND RESULTS: We measured endothelium-derived clotting factors and assayed platelet aggregation in 64 patients (26 adults and 38 children) with PPH before long-term PGI2 therapy. Repeat studies were performed in 42 patients (18 adults, 24 children) after one year of PGI2 therapy. At baseline, 87% of adults and 79% of children had abnormal platelet aggregation. In addition, factor VIII, von Willebrand (vW) antigen, and ristocetin cofactor levels were abnormally high in 92%, 72%, and 52%, respectively, of the adults versus 29%, 16%, and 16%, respectively, of the children (P<.005 adults versus children). With long-term PGI2, platelet aggregation normalized in 83% of the adults and 80% of the children who had platelet aggregation abnormalities at baseline (P<.01). Factor VIII, vW antigen, and ristocetin cofactor also decreased with long-term PGI2 in both groups (P<.02). The ratio of ristocetin cofactor to vW antigen, which may reflect biological activity of vW factor, increased with long-term PGI2 in adults from an abnormally low level (0.6+/-0.2) to normal level (1.10+/-0.4), and in children the ratio increased from 0.8+/-0.3 to 1.3+/-0.4 (normal, 0.8 to 1.4). CONCLUSIONS: Alterations in the coagulation system may contribute to the pathogenesis of PPH; the normalization of these endothelial markers concomitant with improvement in hemodynamic parameters with long-term PGI2 suggests that long-term PGI2 remodels the pulmonary vascular bed with subsequent decreases in endothelial cell injury and hypercoagulability.
Registry Numbers: 35121-78-9 (Epoprostenol)
Institutional address: Department of Pediatrics Columbia University College of Physicians & Surgeons New York NY 10032 USA.
(REFERENCE 46 OF 102) 97234018
Hinderliter AL Willis PW 4th Barst RJ Rich S Rubin LJ Badesch DB Groves BM McGoon MD Tapson VF Bourge RC Brundage BH Koerner SK Langleben D Keller CA Murali S Uretsky BF Koch G Li S Clayton LM Jobsis MM Blackburn SD Jr Crow JW Long WA Effects of long-term infusion of prostacyclin (epoprostenol) on echocardiographic measures of right ventricular structure and function in primary pulmonary hypertension. Primary Pulmonary Hypertension Study Group [see comments]
In: Circulation (1997 Mar 18) 95(6):1479-86
ISSN: 0009-7322
BACKGROUND: Right heart failure is an important cause of morbidity and mortality in primary pulmonary hypertension. In a recent prospective, randomized study of severely symptomatic patients, treatment with prostacyclin (epoprostenol) produced improvements in hemodynamics, quality of life, and survival. This article describes the echocardiographic characteristics of participants in this trial; the relationship of echocardiographic variables to hemodynamic parameters, exercise capacity, and quality of life; and the echocardiographic changes associated with prostacyclin therapy. METHODS AND RESULTS: The 81 patients enrolled in this multicenter trial were randomized to treatment with a long-term infusion of prostacyclin in addition to conventional therapy (n = 41) or conventional therapy alone (n = 40) for 12 weeks. Echocardiograms and assessments of hemodynamics, exercise capacity, and quality of life were performed before and after the treatment phase. On baseline evaluation, patients had marked right ventricular dilatation and dysfunction, abnormal septal curvature, and significant tricuspid regurgitation with a high regurgitant velocity. Pericardial effusions were common. More pronounced abnormalities in right heart structure and function were associated with higher pulmonary arterial and mean right atrial pressures, lower cardiac index, and impaired exercise capacity but had no predictable relationship to quality-of-life indicators. The 12-week infusion of prostacyclin had beneficial effects on right ventricular size, curvature of the interventricular septum, and maximal tricuspid regurgitant jet velocity. CONCLUSIONS: The echocardiographic manifestations of severe primary pulmonary hypertension reflect abnormalities in hemodynamics and exercise capacity. Prostacyclin has beneficial effects on right heart structure and function that may contribute to the clinical improvement and prolonged survival observed with this drug.
Comment in: Circulation 1998 Mar 10;97(9):940-1
Registry Numbers: 35121-78-9 (Epoprostenol)
Institutional address: Department of Medicine University of North Carolina Chapel Hill 27599-7075 USA.
(REFERENCE 47 OF 102) 97207477
Reddy VM Hendricks-Munoz KD Rajasinghe HA Petrossian E Hanley FL Fineman JR Post-cardiopulmonary bypass pulmonary hypertension in lambs with increased pulmonary blood flow. A role for endothelin 1.
In: Circulation (1997 Feb 18) 95(4):1054-61
ISSN: 0009-7322
BACKGROUND: After cardiopulmonary bypass (CPB), pulmonary hypertension and its associated increased vascular reactivity are a major source of morbidity, particularly for children with increased pulmonary blood flow. Although post-CPB pulmonary hypertension is well described, its mechanisms remain incompletely understood. Plasma levels of endothelin 1. a potent vasoactive substance implicated in pulmonary hypertension, are increased after CPB. The purpose of the present study was threefold: to characterize the changes in pulmonary vascular resistance and vascular reactivity induced by hypothermic CPB; to investigate the effects of preexisting increased pulmonary blood flow on these changes; and to better define the role of endothelin 1 in the pathogenesis of post-CPB pulmonary hypertension. METHODS AND RESULTS: Vascular pressures and blood flows were monitored in 14 1-month-old lambs with increased pulmonary blood flow (after in utero placement of an aortopulmonary shunt) and 6 age- matched control lambs. During the 2-hour study period after 105.3 +/- 20.6 minutes of hypothermic CPB the increase in pulmonary vascular resistance was significantly augmented in lambs with increased pulmonary blood flow compared with control lambs (P < .05). Pretreatment with PD 145065 (a nonselective endothelin receptor blocker; 50 micrograms.kg-1.min-1) completely blocked this increase in pulmonary vascular resistance and blocked the increase in pulmonary vascular resistance in response to acute alveolar hypoxia after CPB (96.3 +/- 88.5% versus -9.7 +/- 16.4%; P < .05). Plasma endothelin 1 levels increased after CPB in all lambs. CONCLUSIONS: Preexisting increased pulmonary blood flow alters the response of the pulmonary circulation to hypothermic CPB; the increase in pulmonary vascular resistance induced by CPB is augmented in lambs with increased pulmonary blood flow. Pretreatment with endothelin 1 receptor blockers eliminated the increase in pulmonary vascular resistance and the pulmonary vasoconstricting response to alveolar hypoxia, suggesting a role for endothelin 1 in post-CPB pulmonary hypertension. Endothelin 1 receptor blockers may decrease morbidity in children at risk for pulmonary hypertension after surgical repair with CPB and warrants further study.
Registry Numbers: 153049-49-1 (PD 145065)
Institutional address: Department of Cardiothoracic Surgery University of California San Francisco 94143-0106 USA.
(REFERENCE 48 OF 102) 97080447
Pitton MB Duber C Mayer E Thelen M Hemodynamic effects of nonionic contrast bolus injection and oxygen inhalation during pulmonary angiography in patients with chronic major-vessel thromboembolic pulmonary hypertension.
In: Circulation (1996 Nov 15) 94(10):2485-91
ISSN: 0009-7322
BACKGROUND: Pulmonary angiography is the gold standard for the diagnosis of chronic thromboembolic pulmonary hypertension; however, major complications have been reported. This study evaluates the hemodynamic effects of direct pulmonary nonionic contrast bolus injection and oxygen inhalation in patients with chronic thromboembolic pulmonary hypertension. METHODS AND RESULTS: In 33 patients, hemodynamic parameters were measured after oxygen inhalation and during bolus injection of nonionic contrast medium in a control group (group 1. n = 11), in a group of patients with moderately severe pulmonary hypertension (group 2, n = 9), and in a group with severe pulmonary hypertension (group 3, n = 13). Oxygen inhalation significantly improved oxygen supply. Pulmonary artery pressure and heart rate were reduced, but pulmonary vascular resistance and total pulmonary resistance were not significantly affected. One hundred ninety-eight angiograms were performed selectively on both pulmonary arteries in the posterior-anterior, oblique, and lateral views. Before contrast bolus injection, RAP and PAP significantly increased because of initial inspiration. Contrast bolus injection caused only a minor pressure increase (delta PA systolic, 2.3 +/- 1.4, 2.5 +/- 1.8, and 5.0 +/- 5.2 mm Hg, groups 1, 2, and 3, respectively) without significance between the groups. After the angiography, pulmonary artery pressure was moderately increased, predominantly in group 3, but pulmonary vascular resistance was not significantly changed. Systemic vascular resistance was decreased. Cardiac index increased in groups 1 and 2 but was unchanged in group 3. Systemic pressure therefore decreased in group 3. CONCLUSIONS: We concluded that bolus injection of nonionic contrast medium causes no major hemodynamic effects even in patients with severe chronic thromboembolic pulmonary hypertension. Oxygen contributes to safety during the procedure.
Registry Numbers: 7782-44-7 (Oxygen)
Institutional address: Department of Radiology University Hospital Johannes Gutenberg-University of Mainz Germany.
(REFERENCE 49 OF 102) 97057428
Moulton MJ Creswell LL Ungacta FF Downing SW Szabo BA Pasque MK Magnetic resonance imaging provides evidence for remodeling of the right ventricle after single-lung transplantation for pulmonary hypertension.
In: Circulation (1996 Nov 1) 94(9 Suppl):II312-9
ISSN: 0009-7322
BACKGROUND: In end-stage pulmonary hypertension (PH), the degree of right ventricular (RV) dysfunction has been considered so severe as to require combined heart-lung transplantation. Nevertheless, left ventricular (LV) and RV hemodynamics return to relatively normal levels after single-lung transplantation (SLT) alone. Accordingly, to test the hypothesis that LV and RV systolic function improves after SLT and that the dilated, thick-walled RV reverts to more normal geometry, we used cine MRI and finite-element (FE) analysis to study patients with end-stage PH. METHODS AND RESULTS: Seven patients with end-stage PH underwent cine MRI before and after SLT, and eight normal volunteers were also imaged with cine MRI. Short-axis images at the midventricular level were analyzed with customized image- processing software. The LV and RV ejection fractions, velocity of fiber shortening, RV end-diastolic (ED) and end-systolic (ES) chamber areas, and RV ES and ED wall thicknesses were calculated directly from the MRI images. Two-dimensional FE models of the heart were constructed from the MRI images at early diastole. LV and RV pressures were measured in the patients with a cardiac catheterization before and after SLT. Models were solved to yield diastolic LV, RV, and septal wall stresses. By use of a nonlinear optimization algorithm, LV and RV diastolic maternal properties were determined by minimization of the leastsquares difference between FE model-predicted and MRI-measured LV, RV, and epicardial chamber areas and circumferences. The results demonstrated a substantial reduction in RV wall stress after SLT (1.8 x 10(5) dynes/cm2 pre-SLT to 2 x 10(4) dynes/cm2 post-SLT; P < .001). The average RV diastolic elastic modulus was reduced significantly after SLT (1.5 x 10(6) dynes/cm2 pre-SLT to 1 x 10(5) dynes/cm2 post-SLT; P = .01), but there was no change in the LV elastic modulus. RV velocity of fractional shortening increased significantly after SLT (0.23 pre-SLT to 0.58 post-SLT, P = .02), and RV ED and ES wall thicknesses were reduced significantly (ED, 0.86 cm pre-SLT to 0.65 cm post-SLT, P = .03 and ES, 1.06 cm pre-SLT to 0.72 cm post-SLT, P = .005). CONCLUSIONS: These results provide evidence supporting the contention that LV and RV systolic function improved after SLT for end-stage PH and that the RV underwent significant remodeling within 3 to 6 months after lung transplantation.
Institutional address: Department of Surgery Washington University St Louis Mo. USA.
(REFERENCE 50 OF 102) 97057419
Chau EM Bailey KR Mahoney DW Frantz RP McGregor CG Daly RC Edwards BS Olson LJ Rodeheffer RJ Predictors of reversibility of pulmonary hypertension in cardiac transplant recipients in the first postoperative year.
In: Circulation (1996 Nov 1) 94(9 Suppl):II267-72
ISSN: 0009-7322
BACKGROUND: Pulmonary hypertension remains a risk factor for early postoperative mortality in heart transplantation and may reduce the long-term benefits of the procedure. This study was undertaken to assess the value of baseline hemodynamic studies with nitroprusside used to predict the degree of postoperative reversibility of pulmonary hypertension in cardiac transplant recipients and to identify clinical risk factors for fixed pulmonary hypertension. METHODS AND RESULTS: Hemodynamic data from 55 consecutive patients who underwent orthotopic cardiac transplantation from June 1988 through September 1993 were analyzed. The effects of nitroprusside and transplantation on pulmonary artery pressure, cardiac output, and pulmonary vascular resistance were compared. Multiple regression analysis was used to identify the predictors of reversibility of pulmonary hypertension. Nitroprusside reduced pulmonary vascular resistance by increasing cardiac output and, to a lesser extent, by reducing the transpulmonary gradient. Pulmonary hypertension was less reversible in patients with ischemic heart disease (versus dilated cardiomyopathy) and in former smokers (versus nonsmokers). Patients with nonischemic heart failure and no smoking history had significantly lower posttransplant pulmonary vascular resistance (1.24 +/- 0.45 Wood units) than ischemic patients (who were all former smokers; 2.20 +/- 1.01 wood units) or nonischemic former smokers (1.72 +/- 0.70 Wood units). The correlation of pulmonary vascular resistance during nitroprusside challenge with posttransplant pulmonary vascular resistance was better than that of baseline pulmonary vascular resistance with posttransplant pulmonary vascular resistance. CONCLUSIONS: Nitroprusside testing improves the prediction of late posttransplant pulmonary vascular resistance; hence, it provides data that may be relevant to both early operative risk and later long-term effectiveness of cardiac transplantation. The finding of increased risk of fixed pulmonary hypertension associated with ischemic heart disease and smoking suggests that underlying atherosclerotic vascular disease may contribute to the irreversibility of pulmonary vascular resistance.
Registry Numbers: 15078-28-1 (Nitroprusside)
Institutional address: Department of Biostatics Mayo Clinic Rochester Minn 55905 USA.
(REFERENCE 51 OF 102) 97027533
Nong Z Stassen JM Moons L Collen D Janssens S Inhibition of tissue angiotensin-converting enzyme with quinapril reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling.
In: Circulation (1996 Oct 15) 94(8):1941-7
ISSN: 0009-7322
BACKGROUND: Angiotensin II may contribute to hypoxic pulmonary hypertension via its vasoconstrictor and growth-stimulatory effects on vascular smooth muscle cells (VSMCs). Therefore, the use of ACE inhibitors might reduce hypoxic pulmonary hypertension by decreasing pulmonary vasomotor tone or vascular remodeling. METHODS AND RESULTS: Pulmonary hemodynamics and vascular remodeling were compared in chronically hypoxic (FIO2 = 0.10) rats treated with 0, 1, and 10 mg.kg-1.d-1 quinapril, a potent tissue ACE inhibitor, both during and after the development of pulmonary hypertension. Quinapril reduced the development of pulmonary hypertension after 12 days of hypoxia from 26 +/- 1 to 19 +/- 1 mm Hg (P < .05). When started in established pulmonary hypertension, quinapril reduced pulmonary artery pressure and total pulmonary resistance index from 29 +/- 1 to 25 +/- 1 mm Hg and from 0.136 +/- 0.01 to 0.101 +/- 0.005 mm Hg .mL- 1.min-1 per kg, respectively (P < .05). Chronically hypoxic rats showed a small pulmonary vasoconstrictor response that was not affected by quinapril. In contrast, percent medial thickness in alveolar duct blood vessels was reduced by quinapril treatment both in developing and in established pulmonary hypertension (10.0 +/- 0.2% versus 8.9 +/- 0.1% [P < .05] and 11.2 +/- 0.2% versus 9.1 +/- 0.2% [P < .05], respectively). 5'-Bromo-deoxyuridine-positive VSMCs were detected in 56 +/- 3% of hypoxic control pulmonary resistance vessels versus 41 +/- 3% of vessels after quinapril treatment (P < .05). CONCLUSIONS: Pulmonary ACE and angiotensin II contribute to the development and maintenance of hypoxic pulmonary hypertension in rats. ACE inhibition with quinapril reduces the development of hypoxic pulmonary hypertension and in part reverses established pulmonary hypertension, most likely via inhibition of pulmonary VSMC proliferation and/or growth.
Registry Numbers: 59-14-3 (Bromodeoxyuridine) 82586-55-8 (quinapril)
Institutional address: Center for Transgene Technology and Gene Therapy University Hospital Gasthuisberg University of Leuven Belgium.
(REFERENCE 52 OF 102) 96314290
Williamson DJ Hayward C Rogers P Wallman LL Sturgess AD Penny R Macdonald PS Acute hemodynamic responses to inhaled nitric oxide in patients with limited scleroderma and isolated pulmonary hypertension.
In: Circulation (1996 Aug 1) 94(3):477-82
ISSN: 0009-7322
BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator that reduces pulmonary vascular resistance (PVR) in patients with primary pulmonary hypertension. Their responses to inhaled NO predict their responses to other vasodilators, such as prostacyclin, and provide an estimate of the "fixed" component of their increased PVR. Some patients with limited cutaneous systemic sclerosis develop isolated pulmonary hypertension with a similar clinical course. Therefore, we have measured the acute hemodynamic response to inhaled NO in such patients. METHODS AND RESULTS: Seven patients were studied during inhalation of increasing concentrations of NO (0 to 80 ppm). Complete hemodynamic data were collected on five patients. They demonstrated a selective, dose-dependent, and rapidly reversible fall in PVR (34%) and mean pulmonary artery pressure (17%). There was a nonsignificant increase in cardiac index but no change in mean arterial pressure or systemic vascular resistance. The mean right atrial pressure fell (27%), but there was no change in pulmonary artery occlusion pressure. Of the seven patients, five responded to inhaled NO ( < or = 40 ppm) with a decrease in total pulmonary resistance of at least 20%. CONCLUSIONS: Inhaled NO is an effective and selective pulmonary vasodilator in a significant number of patients with pulmonary hypertension associated with limited cutaneous systemic sclerosis. It may be useful in determining the potentially reversible contribution to the increased PVR and should be considered for patients with acute pulmonary vascular crisis.
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Centre for Immunology St. Vincent's Hospital Darlinghurst NSW Australia. j.williamson@cft.unsw.edu.au
(REFERENCE 53 OF 102) 99005409
Robbins IM Colvin EV Doyle TP Kemp WE Loyd JE McMahon WS Kay GN Pulmonary vein stenosis after catheter ablation of atrial fibrillation.
In: Circulation (1998 Oct 27) 98(17):1769-75
ISSN: 0009-7322
BACKGROUND: This report describes the complication of pulmonary vein stenosis with resultant severe pulmonary hypertension that developed in 2 patients after successful catheter ablation of chronic atrial fibrillation. METHODS AND RESULTS: Three months after successful catheter ablation of atrial fibrillation, both patients developed progressive dyspnea and pulmonary hypertension. Both were found to have severe stenosis of all 4 pulmonary veins near the junction with the left atrium. Balloon dilation of the stenotic pulmonary veins was performed in these patients, with improvement in dyspnea and pulmonary hypertension. CONCLUSIONS: The complication of pulmonary vein stenosis is potentially life-threatening, and the application of radiofrequency current within the pulmonary veins with standard catheter technology should be avoided. This complication can be treated with balloon dilation, although the long-term course is unknown.
Institutional address: University of Alabama at Birmingham and Vanderbilt University Nashville TN USA.
(REFERENCE 54 OF 102) 98434431
Yuan JX Aldinger AM Juhaszova M Wang J Conte JV Jr Gaine SP Orens JB Rubin LJ Dysfunctional voltage-gated K+ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension.
In: Circulation (1998 Oct 6) 98(14):1400-6
ISSN: 0009-7322
BACKGROUND: Primary pulmonary hypertension (PPH) is a rare disease of unknown cause. Although PPH and secondary pulmonary hypertension (SPH) share many clinical and pathological characteristics, their origins may be disparate. In pulmonary artery smooth muscle cells (PASMCs), the activity of voltage-gated K+ (KV) channels governs membrane potential (Em) and regulates cytosolic free Ca2+ concentration ([Ca2+]cyt). A rise in [Ca2+]cyt is a trigger of vasoconstriction and a stimulus of smooth muscle proliferation. METHODS and RESULTS: Fluorescence microscopy and patch clamp techniques were used to measure [Ca2+]cyt, Em, and KV currents in PASMCs. Mean pulmonary arterial pressures were comparable (46+/-4 and 53+/-4 mm Hg; P=0.30) in SPH and PPH patients. However, PPH-PASMCs had a higher resting [Ca2+]cyt than cells from patients with SPH and nonpulmonary hypertension disease. Consistently, PPH-PASMCs had a more depolarized Em than SPH-PASMCs. Furthermore, KV currents were significantly diminished in PPH-PASMCs. Because of the dysfunctional KV channels, the response of [Ca2+]cyt to the KV channel blocker 4- aminopyridine was significantly attenuated in PPH-PASMCs, whereas the response to 60 mmol/L K+ was comparable to that in SPH-PASMCs. CONCLUSIONS: These results indicate that KV channel function in PPH- PASMCs is inhibited compared with SPH-PASMCs. The resulting membrane depolarization and increase in [Ca2+]cyt lead to pulmonary vasoconstriction and PASMC proliferation. Our data suggest that defects in PASMC KV channels in PPH patients may be a unique mechanism involved in initiating and maintaining pulmonary vasoconstriction and appear to play a role in the pathogenesis of PPH.
Registry Numbers: 7440-09-7 (Potassium) 7440-70-2 (Calcium)
Institutional address: Departments of Medicine Physiology and Surgery University of Maryland School of Medicine Baltimore Md USA.
(REFERENCE 55 OF 102) 95393572
Mehta S Stewart DJ Langleben D Levy RD Short-term pulmonary vasodilation with L-arginine in pulmonary hypertension.
In: Circulation (1995 Sep 15) 92(6):1539-45
ISSN: 0009-7322
BACKGROUND: Endothelial dysfunction may contribute to the pathogenesis of pulmonary hypertension through impaired production of the endothelium-derived vasodilator nitric oxide (NO). L-Arginine, the substrate for NO synthase (NOS), has a vasodilatory effect in systemic vascular beds and can correct abnormal endothelium-dependent vasodilation. It has been suggested that these two effects of L- arginine are mediated through NOS metabolism and enhanced NO production. Therefore, we assessed the short-term pulmonary hemodynamic effects of exogenous L-arginine in patients with pulmonary hypertension of various origins. METHODS AND RESULTS: During continuous hemodynamic monitoring, 10 subjects with pulmonary hypertension (mean pulmonary artery pressure [PAP], 54 +/- 5 mm Hg [mean +/- SEM]) received a 30-minute control infusion of hypertonic saline followed by a 30-minute infusion of 500 mg/kg of L-arginine. The hemodynamic effects of L-arginine were compared with those of prostacyclin titrated to maximally tolerated doses. The hemodynamic response to L-arginine was also studied in 5 subjects with heart failure but without pulmonary hypertension (mean PAP, 20 +/- 2 mm Hg) and 5 healthy control subjects. In subjects with pulmonary hypertension, infusion of L-arginine reduced mean PAP by 15.8 +/- 3.6% (P < .005) and pulmonary vascular resistance (PVR) by 27.6 +/- 5.8% (P < .005) compared with decreases of 13.0 +/- 5.5% (P < .005) and 46.6 +/- 6.2% (P < .005), respectively, with prostacyclin. L- Arginine infusion also increased the mean plasma level of L-arginine from 59 +/- 6 mumol/L to 10,726 +/- 868 mumol/L (P < .005), which was associated with a significant increase in the plasma level of L- citrulline, the immediate product of NOS metabolism of L-arginine. Moreover, the peak plasma level of L-citrulline correlated significantly with the reductions in mean PAP (r = .71, P < .05) and PVR (r = .70, P < .05), consistent with vasodilation mediated by NOS metabolism of exogenous L-arginine and increased NO production. L- Arginine also had a modest hypotensive effect in healthy control subjects and reduced systemic vascular resistance in subjects with heart failure in the absence of pulmonary hypertension. However, only small reductions in absolute pulmonary vascular resistance were observed in this latter group in response to L-arginine that did not reach significance. CONCLUSIONS: An exaggerated short-term pulmonary vasodilatory response to L-arginine in patients with pulmonary hypertension suggests a relative impairment in pulmonary vascular endothelial NO production that may contribute to increased pulmonary vascular tone and thus be important in the pathophysiology of pulmonary hypertension.
Registry Numbers: 10102-43-9 (Nitric Oxide) 35121-78-9 (Epoprostenol) 7004-12-8 (Arginine)
Institutional address: Respiratory Division Royal Victoria Hospital Montreal Quebec Canada.
(REFERENCE 56 OF 102) 95361155
Reddy VM Meyrick B Wong J Khoor A Liddicoat JR Hanley FL Fineman JR In utero placement of aortopulmonary shunts. A model of postnatal pulmonary hypertension with increased pulmonary blood flow in lambs.
In: Circulation (1995 Aug 1) 92(3):606-13
ISSN: 0009-7322
BACKGROUND: The development of pulmonary hypertension and its associated increased vascular reactivity is a common accompaniment of congenital heart disease with increased pulmonary blood flow. Although the morphology of the pulmonary vascular changes is well described, the mechanisms of vascular remodeling and increased reactivity remain incompletely understood. METHODS AND RESULTS: To elucidate these mechanisms, we established an accurate and reliable experimental model of pulmonary hypertension with increased pulmonary blood flow. An aortopulmonary shunt was created with an 8.0-mm expanded polytetrafluoroethylene vascular graft in 11 late-gestation fetal lambs. At 1 month of age, shunted lambs had a pulmonary-to- systemic blood flow ratio of 2.2 +/- 1.2. Compared with 11 age- matched control lambs, mean pulmonary arterial pressure (44.8 +/- 11.7 versus 16.2 +/- 2.9 mm Hg) and the ratio of pulmonary to systemic arterial pressure were significantly increased (P < .05). Pulmonary vascular resistance was not significantly increased. The pulmonary vasoconstricting response to the infusion of U46619 (a thromboxane A2 mimic) or acute alveolar hypoxia also was augmented in the shunted lambs. Morphometric analysis of the barium-filled pulmonary artery bed revealed medial hypertrophy, abnormal extension of muscle distally into the walls of the intra-acinar arteries, and increased numbers of barium-filled intra-acinar arteries. CONCLUSIONS: In utero placement of aortopulmonary shunts reproduces the aberrant hemodynamic state of children with cogenital heart disease with left-to-right shunts; postnatal pulmonary hypertension, increased pulmonary blood flow, and vascular remodeling. In addition, the lambs have a unique paradoxical increase in pulmonary vascular volume that attenuates an increase in pulmonary vascular resistance. This experimental preparation provides a useful and consistent model for the study of the pathogenesis of pulmonary hypertension.
Institutional address: Department of Cardiothoracic Surgery University of California San Francisco 94143-0106 USA.
(REFERENCE 57 OF 102) 95361149
Belenkie I Horne SG Dani R Smith ER Tyberg JV Effects of aortic constriction during experimental acute right ventricular pressure loading. Further insights into diastolic and systolic ventricular interaction.
In: Circulation (1995 Aug 1) 92(3):546-54
ISSN: 0009-7322
BACKGROUND: Acute right ventricular (RV) hypertension may result in hemodynamic collapse. The associated reduction in left ventricular (LV) end-diastolic volume is thought to result from reduced RV output (secondary to RV ischemia) and adverse direct ventricular interaction. Aortic constriction improves cardiac function in these circumstances; this has been attributed to a reversal of the RV ischemia caused by an increased coronary perfusion pressure. We hypothesized that altered ventricular interaction, potentially via altered septal mechanics, may also contribute to the beneficial effects of aortic constriction. METHODS AND RESULTS: We instrumented nine dogs with ultrasonic dimension crystals to measure RV segment length, septum-to-RV free wall and septum-to-LV free wall diameters, and LV anterioposterior diameter. Catheter-tipped manometers were used to measure LV and RV pressures. Pericardial pressure was measured with flat, liquid-containing balloon transducers. Inflatable cuff constrictors were placed on the pulmonary artery (PA) and aorta, and a flow probe was placed on the PA. The right coronary artery (RCA) was perfused independently by a roller pump calibrated for flow. During moderate PA constriction, while RCA pressure was maintained at control level, RCA flow did not change significantly (15.8 +/- 6.2 to 16.9 +/- 11.5 mL/min) and was similar during severe PA constriction (18.6 +/- 9.8 mL/min). During severe PA constriction, RV stroke volume decreased from a control value of 10.3 +/- 4.9 to 2.3 +/- 1.4 mL/beat (P < .05). When aortic constriction was added while RCA pressure was maintained at control level, there was an increase in RV stroke volume to 4.5 +/- 2.0 mL/beat (P < .05) with no associated change in RCA flow (17.8 +/- 9.5 mL/min). However, pressure-dimension loops clearly demonstrated changes in diastolic and systolic ventricular interaction; with aortic constriction, there was a large increase in the transeptal pressure gradient associated with a rightward septal shift. During either isolated severe PA constriction or simultaneous severe PA and aortic constriction, RCA flow was increased until RCA pressure was approximately equal to that in the aorta. This produced an increase in RCA flow of 50% (P < .05); however, this increase in coronary flow was ineffective in improving any measure of RV function. CONCLUSIONS: In this model of acute RV hypertension, aortic constriction improves cardiac function, at least in part, by altering ventricular interaction independent of changes in RCA flow. Changes in RCA flow do not appear to have a significant impact on cardiac function in this model in which coronary artery pressure was maintained at normal or increased levels.
Institutional address: Department of Medicine Faculty of Medicine University of Calgary Alberta Canada.
(REFERENCE 58 OF 102) 95308742
Okada M Yamashita C Okada M Okada K Role of endothelin-1 in beagles with dehydromonocrotaline-induced pulmonary hypertension.
In: Circulation (1995 Jul 1) 92(1):114-9
ISSN: 0009-7322
BACKGROUND: Although plasma levels of endothelin-1 (ET-1) increase in patients with pulmonary hypertension (PH), its role in PH is unknown. We investigated the contribution of endogenous ET-1 to cardiopulmonary changes in beagles with dehydromonocrotaline (DMCT)- induced PH. METHODS AND RESULTS: Eight 3-month-old beagles were given a single injection of 3 mg/kg DMCT via the right atrium. During the 8 weeks after injection, the mean pulmonary arterial pressure (PAP) and plasma ET-1 level increased significantly from 11.6 +/- 2.3 to 35.9 +/- 7.1 mm Hg and from 1.24 +/- 0.25 to 3.25 +/- 0.94 pg/mL, respectively. In controls, ET-1 infusion elevated the systemic arterial pressure (SAP) but did not alter PAP. In PH beagles, ET-1 infusion increased SAP, which was attenuated by FR139317 (an endothelin type [ET] A receptor antagonist), and produced a dose- dependent decrease in PAP, which was attenuated by RES-701-1 (an ETB receptor antagonist). In PH beagles, FR139317 infusion decreased PAP, and RES-701-1 infusion increased PAP. Sarafotoxin S6c (an ETB agonist) infusion decreased PAP in PH beagles. CONCLUSIONS: These results suggest that endogenous ET-1 is elevated in PH disease and may mitigate PH by acting on ETB receptors.
Registry Numbers: 142375-60-8 (FR 139317) 151308-34-8 (RES 701-1) 23291-96-5 (monocrotaline pyrrole) 315-22-0 (Monocrotaline)
Institutional address: Department of Surgery Kobe University School of Medicine Japan.
(REFERENCE 59 OF 102) 95202825
Kerstein D Levy PS Hsu DT Hordof AJ Gersony WM Barst RJ Blade balloon atrial septostomy in patients with severe primary pulmonary hypertension.
In: Circulation (1995 Apr 1) 91(7):2028-35
ISSN: 0009-7322
BACKGROUND: Patients with severe primary pulmonary hypertension have a poor prognosis, but those with a patent foramen ovale may survive longer. A few reports of clinical improvement after blade balloon atrial septostomy in patients with severe pulmonary vascular disease have appeared. The purpose of this study was to systematically evaluate the effects of blade balloon atrial septostomy on clinical signs and symptoms, hemodynamics, and survival in patients with severe primary pulmonary hypertension. METHODS AND RESULTS: Blade balloon atrial septostomy was performed on 15 children and young adults with severe primary pulmonary hypertension. Despite maximal medical therapy, prior to septostomy all patients had recurrent syncope and 8 had severe right heart failure. Thirteen patients survived the procedure. After blade balloon atrial septostomy, no patient experienced further syncope, and signs and symptoms of right heart failure improved in all New York Heart Association Class IV patients. Within 24 hours after the procedure and at follow-up catheterization 7 to 27 months after septostomy, there was a significant increase in cardiac index, resulting in an increase in systemic oxygen transport. There was improved long-term survival in the 13 patients who survived blade balloon atrial septostomy compared with similar groups of primary pulmonary hypertension patients who received standard therapy (P < .05). CONCLUSIONS: Blade balloon atrial septostomy resulted in clinical and hemodynamic improvement and improved survival in selected patients with severe primary pulmonary hypertension.
Institutional address: Division of Pediatric Cardiology Columbia University College of Physicians and Surgeons New York NY 10032.
(REFERENCE 60 OF 102) 95129221
Moser KM Fedullo PF Finkbeiner WE Golden J Do patients with primary pulmonary hypertension develop extensive central thrombi?
In: Circulation (1995 Feb 1) 91(3):741-5
ISSN: 0009-7322
BACKGROUND: Distinguishing chronic major vessel thromboembolic pulmonary hypertension from primary pulmonary hypertension is critical because the treatment options differ markedly. Surgical thromboendarterectomy is potentially curative in the former condition, whereas oxygen, vasodilators, perhaps anticoagulation, and lung transplantation are the options for the latter. The development of large thrombi in the main, right, or left pulmonary arteries has not been previously described in patients with primary pulmonary hypertension. METHODS AND RESULTS: Three pulmonary hypertensive patients with massive thrombi in the central pulmonary arteries are described. The data indicate that the large central thrombi in these three patients were not hemodynamically significant. In none did perfusion lung scans demonstrate segmental or larger defects. CONCLUSIONS: Large central thrombi can develop in patients with primary pulmonary hypertension. Perfusion lung scans that do not demonstrate segmental or larger defects should alert physicians to this possibility. Chest computed tomography and other studies identifying such thrombi are not adequate in distinguishing such a development from operable chronic major vessel thromboembolic hypertension. Careful review of lobar and segmental artery findings and the pulmonary angiogram, angioscopy, and cardiac catheterization data demonstrating the hemodynamic significance (or lack thereof) of these thrombi are essential in making this important distinction. Furthermore, these observations may constitute an additional indication for anticoagulant therapy in primary pulmonary hypertension.
Institutional address: Department of Medicine University of California San Diego School of Medicine 92103.
(REFERENCE 61 OF 102) 95103753
Goerre S Wenk M Bartsch P Luscher TF Niroomand F Hohenhaus E Oelz O Reinhart WH Endothelin-1 in pulmonary hypertension associated with high-altitude exposure.
In: Circulation (1995 Jan 15) 91(2):359-64
ISSN: 0009-7322
BACKGROUND: Endothelin-1 is involved in chronic pulmonary hypertension. Its role in acute pulmonary hypertension due to hypoxia in humans is not clear. We therefore studied the influence of hypoxia caused by exposure to high altitude on plasma endothelin-1 levels, arterial blood gases, and pulmonary arterial pressure in subjects taking nifedipine or placebo. METHODS AND RESULTS: Twenty-two healthy volunteers were investigated at low altitude (490 m) and high altitude (4559 m). Arterial blood gases were analyzed immediately, endothelin-1 was measured by radioimmunoassay, and pulmonary artery pressure was assessed by Doppler echocardiography. After baseline investigations, the mountaineers were allocated in a randomized double-blind fashion to receive either placebo or nifedipine (20 mg TID) during rapid ascent to high altitude within 22 hours. Tests were repeated at the high-altitude research laboratories located in the Capanna "Regina Margherita" (Italy, 4559 m). Plasma endothelin-1 was increased twofold at high altitude (5.9 +/- 2.2 pg/mL compared with 2.9 +/- 1.1 pg/mL, P < .05), was inversely related to arterial PO2 (r = -.46, P < .001), and correlated with pulmonary artery pressure (r = .52, P < .002). At high altitude, arterial endothelin-1 was lower (4.3 +/- 1.6 pg/mL) than venous endothelin-1 (5.9 +/= 2.2 pg/mL, P < .001), indicating either predominant production in the venous vasculature or pronounced clearance in the pulmonary circulation. The calcium antagonist nifedipine, which lowered pulmonary artery pressure at high altitude (32 +/- 5 versus 42 +/- 11 mm Hg, P < .05), had no influence on plasma endothelin-1 levels. The administration of 35% O2 at high altitude normalized arterial PO2, tended to decrease endothelin-1, and decreased pulmonary artery pressure accordingly. CONCLUSIONS: We conclude that plasma endothelin-1 is increased at high altitude, but whether or not it represents an important pathogenetic factor for pulmonary hypertension remains to be investigated.
Registry Numbers: 21829-25-4 (Nifedipine) 7782-44-7 (Oxygen)
Institutional address: Kantonsspital Chur Switzerland.
(REFERENCE 62 OF 102) 95087143
Fuse S Kamiya T Plasma thromboxane B2 concentration in pulmonary hypertension associated with congenital heart disease.
In: Circulation (1994 Dec) 90(6):2952-5
ISSN: 0009-7322
BACKGROUND: We investigated the plasma concentration of thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2), to assess platelet activation in 78 patients who had pulmonary hypertension associated with congenital heart disease (PH group) and 16 patients with almost normal hemodynamics (control group). METHODS AND RESULTS: The PH group was divided into two subgroups: pulmonary vascular resistance (Rp) < or = 10 U/m2 (Rp < or = 10 group) and > 10 U/m2 (Rp > 10 group). In addition, the Rp < or = 10 group was divided on the basis of clinical symptoms into groups with dyspnea (dyspnea[+] group) and without dyspnea (dyspnea[-] group). Plasma TXB2 levels were measured by radioimmunoassay. Plasma TXB2 levels in the three groups (control, Rp < or = 10, and Rp > 10) were significantly different (P < .005); the TXB2 levels in the Rp < or = 10 group were significantly higher than the others. Among the Rp < or = 10 patients, the plasma TXB2 levels were significantly higher in the dyspnea(+) group than in the dyspnea(-) group (P < .0001). In addition, the pulmonary-to-systemic flow ratio and pulmonary blood flow divided by body surface area were significantly higher in the dyspnea(+) group than in the dyspnea(-) group (P < .02 and P < .002, respectively). CONCLUSIONS: These findings suggest that platelet activation led to increased TXA2 release in patients with pulmonary hypertension, especially those with dyspnea and Rp < or = 10. TXA2 release from platelets probably caused constriction of the pulmonary arterioles and the bronchi, thus worsening pulmonary hypertension and dyspnea in these patients. In the patients with high Rp values, it was considered that the number of pulmonary arterioles where platelets could be activated had been reduced.
Registry Numbers: 54397-85-2 (Thromboxane B2)
Institutional address: National Cardiovascular Center Osaka Japan.
(REFERENCE 63 OF 102) 94373935
Brook MM Fineman JR Bolinger AM Wong AF Heymann MA Soifer SJ Use of ATP-MgCl2 in the evaluation and treatment of children with pulmonary hypertension secondary to congenital heart defects.
In: Circulation (1994 Sep) 90(3):1287-93
ISSN: 0009-7322
BACKGROUND: Pulmonary hypertension results in increased morbidity and mortality in children after surgical repair of congenital heart defects. Various vasodilators have been unsuccessful in providing preferential pulmonary vasodilation in these patients. Identification of a more preferential pulmonary vasodilator would improve the assessment, management, and outcome of these children. To determine whether ATP-MgCl2 is a preferential pulmonary vasodilator in children with pulmonary hypertension secondary to congenital heart defects, ATP-MgCl2 was administered during routine cardiac catheterization, and the effects were compared with tolazoline. In addition, ATP-MgCl2 was infused intravenously during episodes of postoperative pulmonary hypertension. METHODS AND RESULTS: During cardiac catheterization in 28 children, the effect of ATP-MgCl2 on the pulmonary artery pressure (PAP) and pulmonary vascular resistance index (Rp) was compared with tolazoline. ATP-MgCl2 (0.1 mg of ATP per kilogram per minute) decreased mean PAP by 24% (P < .05) and Rp by 47% (P < .05) without changing mean systemic arterial pressure or systemic vascular resistance. These effects were comparable to those of tolazoline (1 mg/kg). ATP-MgCl2 produced no significant side effects; tolazoline caused tachycardia, nausea, and vomiting. After cardiac surgery in 7 patients, ATP-MgCl2 decreased PAP by 14% (P < .05) and systemic arterial pressure by 6% (P < .05) and eliminated pulmonary hypertensive crises in 3 of 3 patients. CONCLUSIONS: ATP-MgCl2 is a safe, effective, and preferential pulmonary vasodilator in children with pulmonary hypertension secondary to congenital heart defects. It is useful for evaluating pulmonary vasoreactivity during cardiac catheterization and for treating pulmonary hypertension after cardiac surgery.
Registry Numbers: 56-65-5 (Adenosine Triphosphate) 59-98-3 (Tolazoline)
Institutional address: Department of Pediatrics University of California San Francisco 94143-0214.
(REFERENCE 64 OF 102) 97386395
Mitani Y Maruyama K Sakurai M Prolonged administration of L-arginine ameliorates chronic pulmonary hypertension and pulmonary vascular remodeling in rats [see comments]
In: Circulation (1997 Jul 15) 96(2):689-97
ISSN: 0009-7322
BACKGROUND: Endothelium-dependent nitric oxide-mediated vasodilation is impaired in rats with pulmonary hypertension (PH) induced by chronic hypoxia or by monocrotaline injection. We therefore investigated whether the prolonged administration of the nitric oxide precursor L-arginine would alleviate PH in both rat models. METHODS AND RESULTS: Fifty-nine rats were exposed to hypobaric hypoxia (380 mm Hg, 10 days) or room air and injected intraperitoneally with L- arginine (500 mg/kg), D-arginine (500 mg/kg), or saline once daily from day -3 to day 10. An additional 38 rats injected subcutaneously with monocrotaline (60 mg/kg) or saline were treated similarly with L- arginine or saline from day -3 to day 17. At the end of the experiment, awake mean pulmonary arterial pressure was determined. The heart was dissected to weigh the right ventricle, and the lungs were obtained for vascular morphometric analysis. Hypoxic rats developed PH (30.8+/-0.7 versus 19.2+/-0.4 mm Hg in controls; P<.05) and right ventricular hypertrophy. Their pulmonary arterial wall thickness and the proportion of muscular arteries in the peripheral arteries increased. L-Arginine but not D-arginine reduced PH (24.8+/- 0.7 mm Hg; P<.05), right ventricular hypertrophy, and pulmonary vascular disease. Monocrotaline rats developed PH (34.9+/-2.1 versus 18.8+/-1.2 mm Hg in controls; P<.05), right ventricular hypertrophy, and pulmonary vascular disease. Again, L-arginine reduced PH (24.3+/- 1.7 mm Hg; P<.05), right ventricular hypertrophy, and pulmonary vascular disease. CONCLUSIONS: We conclude that L-arginine ameliorated the changes associated with PH in rats, perhaps by modifying the endogenous nitric oxide production.
Comment in: Circulation 1997 Jul 15;96(2):379-82
Registry Numbers: 315-22-0 (Monocrotaline) 7004-12-8 (Arginine)
Institutional address: Department of Pediatrics Mie University School of Medicine Tsu Japan.
(REFERENCE 65 OF 102) 97336678
Morse JH Jones AC Barst RJ Hodge SE Wilhelmsen KC Nygaard TG Mapping of familial primary pulmonary hypertension locus (PPH1) to chromosome 2q31-q32.
In: Circulation (1997 Jun 17) 95(12):2603-6
ISSN: 0009-7322
BACKGROUND: The pathogenesis of primary pulmonary hypertension (PPH) is unknown, although in some instances families with multiple affected members suggest a genetic etiology. METHODS AND RESULTS: We used microsatellite markers and linkage analysis in a large family with PPH to determine the chromosomal location of their disease gene. We tested a second, ethnically distinct, family for cosegregation of disease with markers from the linked region. We mapped the disease locus PPH1; GDB/HUGO designation (GDB:1381541; July 1996), approved when this work was accepted for publication in abstract form (Circulation. 1996;94[suppl I]:1-49.), in these families to a 27-cM region on chromosome 2q31-q32, with a maximum lod score of 3.87 associated with markers D2S350 and D2S364. CONCLUSIONS: Cosegregation of this region with disease in different ethnic groups suggests that we mapped an important locus in familial PPH. Careful study of additional families and sporadic cases will be required to confirm this localization of PPH1 and characterize its overall role.
Institutional address: Department of Medicine Columbia University College of Physicians and Surgeons New York NY 10032 USA. jhm4@columbia.edu
(REFERENCE 66 OF 102) 98289418
Prie S Stewart DJ Dupuis J EndothelinA receptor blockade improves nitric oxide-mediated vasodilation in monocrotaline-induced pulmonary hypertension.
In: Circulation (1998 Jun 2) 97(21):2169-74
ISSN: 0009-7322
BACKGROUND: Nitric oxide (NO) and endothelin (ET) have been implicated in the pathogenesis of pulmonary hypertension (PH). Chronic ETA antagonist therapy reduces PH in monocrotaline (MCT)- treated rats. Interactions between the L-arginine-NO pathway and the ET system have been described. We therefore studied the effect of long-term treatment with an oral ETA antagonist (LU 135252) on NO- related vasodilation in isolated lungs from control rats and rats with MCT-induced PH. METHODS AND RESULTS: Three weeks after MCT injection, PH was associated with an increase in right ventricular pressure (from 27.4 +/- 0.9 to 66.6 +/- 4.1 mm Hg) and a decrease in endothelium-independent vasodilation in response to sodium nitroprusside (10(-10) to 10(-5) mol/L; delta Emax, from 11.1 +/- 0.9 to 2.7 +/- 0.3 mm Hg). Endothelium-dependent vasodilation in response to acetylcholine (10(-9) to 10(-4) mol/L) and the calcium ionophore A23187 (10(-9) to 10(-7) mol/L) remained unaffected. Treatment with LU 135252 did not significantly affect the endothelium-dependent and - independent vasodilations in control rats. However, in MCT-treated rats, LU 135252 therapy significantly reduced right ventricular pressure (39.7 +/- 2.1 mm Hg), potentiated acetylcholine-induced vasodilatation (delta Emax, from 1.6 +/- 0.2 to 3.7 +/- 0.4 mm Hg), and improved the responses to sodium nitroprusside (delta Emax, from 2.7 +/- 0.3 to 5.6 +/- 0.6 mm Hg). LU 135252 did not significantly alter the non-receptor-mediated endothelium-dependent vasodilation to A23187 or pulmonary constitutive NO synthase activity. CONCLUSIONS: MCT PH is associated with a reduced smooth muscle responsiveness to NO but a maintained endothelium-dependent vasodilatory potency. Long- term ETA antagonist therapy not only restores smooth muscle responsiveness to NO but also increases endothelium-dependent dilation in response to acetylcholine. This mechanism may contribute to the therapeutic benefit of ETA antagonists in PH.
Registry Numbers: EC 1.14.13.39 (Nitric-Oxide Synthase) 10102-43-9 (Nitric Oxide) 315-22-0 (Monocrotaline) EC 1.14.13.- (endothelial constitutive nitric oxide synthase)
Institutional address: Department of Medicine Montreal Heart Institute Quebec Canada.
(REFERENCE 67 OF 102) 98254398
Chen EP Craig DM Bittner HB Davis RD Van Trigt P Pharmacological strategies for improving diastolic dysfunction in the setting of chronic pulmonary hypertension.
In: Circulation (1998 Apr 28) 97(16):1606-12
ISSN: 0009-7322
BACKGROUND: Right ventricular (RV) hypertrophy is an adaptive process that occurs in the setting of chronic pulmonary hypertension (CPH) and can lead to alterations in normal RV diastolic properties. This study was designed to investigate the effects of NO and milrinone on RV diastolic dysfunction in the setting of CPH and RV hypertrophy by use of a canine model of monocrotaline pyrrole (MCTP)-induced CPH. METHODS AND RESULTS: Sixteen mongrel dogs (22 to 24 kg) were used. Animals underwent percutaneous pulmonary artery (PA) catheterization to measure pulmonary hemodynamics before and 8 weeks after injection of 3 mg/kg MCTP (n=8) or placebo (control, n=8). Eight weeks after injection, all hearts were instrumented with a PA flow probe, sonomicrometric dimension transducers, and micromanometers. Data were collected at baseline and after both NO and milrinone administration. Diastolic properties were quantified by use of the end-diastolic pressure-volume relationship and the time constant of ventricular isovolumic relaxation. Eight weeks after injection, significant increases in the PA pressure and pulmonary vascular resistance were observed in MCTP dogs. Significant worsening of RV diastolic function occurred in association with significant increases in the ratio of RV dry weight to LV+septal dry weight. NO and milrinone administration both led to significant improvements in RV diastolic properties. CONCLUSIONS: In the setting of MCTP-induced CPH, significant worsening of RV diastolic function was observed in association with significant increases in the ratio of RV dry weight to LV+septal dry weight, suggesting that these changes are partially due to RV hypertrophy. The significant improvement in RV diastolic properties after both NO and milrinone administration suggests that these agents may be effective forms of pharmacological therapy for improving RV diastolic dysfunction in the setting of CPH.
Registry Numbers: 10102-43-9 (Nitric Oxide) 78415-72-2 (milrinone)
Institutional address: Department of Surgery Duke University Medical Center Durham NC USA. epchen@itsa.ucsf.edu
(REFERENCE 68 OF 102) 96156007
Raffy O Azarian R Brenot F Parent F Sitbon O Petitpretz P Herve P Duroux P Dinh-Xuan AT Simonneau G Clinical significance of the pulmonary vasodilator response during short-term infusion of prostacyclin in primary pulmonary hypertension.
In: Circulation (1996 Feb 1) 93(3):484-8
ISSN: 0009-7322
BACKGROUND: The short-term vasodilator response to prostacyclin (PGI2) in patients with primary pulmonary hypertension (PPH) is not only unpredictable but also extremely variable in magnitude. In this retrospective study, we attempted to evaluate in a nonselected population of patients with PPH the degree of vasodilatation achieved during short-term infusion of PGI2 and to investigate whether patients with PPH differed in terms of baseline characteristics and prognoses, according to the level of vasodilatation achieved during initial testing with PGI2. METHODS AND RESULTS: Between 1984 and 1992, 91 consecutive patients with PPH underwent catheterization of the right side of the heart with a short-term vasodilator trial with PGI2 (5 to 10 ng.kg-1.min-1). According to the level of vasodilatation achieved during PGI2 infusion, patients were divided into three groups: nonresponding (NR, n = 40), moderately responding (MR, n = 42), and highly responding (HR, n = 9) patients. All three groups were defined by a decrease in total pulmonary resistance index (TPRi) of < 20%, between 20% and 50%, and > 50%, respectively, relative to control values. Prolonged oral vasodilator therapy was subsequently started only in MR and HR patients. All patients had long-term oral anticoagulant therapy. The survival rate at 2 years (transplant recipients excluded) was significantly higher in HR patients compared with NR and MR patients (62% versus 38% and 47% survivors, respectively; P < .05). Comparisons between groups showed no significant differences in baseline hemodynamics or clinical characteristics except for a longer time between onset of symptoms and diagnosis (ie, first catheterization) of PPH in HR patients than in NR and MR patients (71 +/- 61 versus 35 +/- 34 and 21 +/- 21 months, respectively; P < .05). CONCLUSIONS: In this study, patients with PPH exhibiting a decrease in TPRi > 50% during short-term PGI2 challenge at the time of diagnosis had longer disease evolutions and better prognoses than patients with a lower vasodilator response.
Registry Numbers: 35121-78-9 (Epoprostenol)
Institutional address: Service de Pneumologie et Reanimation Respiratoire Universite Paris-Sud Hopital Antoine Beclere Clamart France.
(REFERENCE 69 OF 102) 96069191
Vincens JJ Temizer D Post JR Edmunds LH Jr Herrmann HC Long-term outcome of cardiac surgery in patients with mitral stenosis and severe pulmonary hypertension.
In: Circulation (1995 Nov 1) 92(9 Suppl):II137-42
ISSN: 0009-7322
BACKGROUND: Pulmonary hypertension increases perioperative risk in patients having mitral valve replacement, but most studies have included patients with mixed mitral valve disease and have not examined long-term outcome. METHODS AND RESULTS: We retrospectively examined the results and predictors of outcome of cardiac surgery in 43 patients (age, 62 +/- 13 years [mean +/- SD]; 81% women) with a primary diagnosis of mitral stenosis and severe pulmonary hypertension (pulmonary artery systolic pressure > or = 60 mm Hg or mean pressure > or = 50 mm Hg). Patients with more than mild mitral regurgitation were excluded. Thirty-eight patients (88%) were in NYHA functional class III or IV, and 11 patients (26%) had an acute presentation requiring urgent surgery. Preoperative hemodynamics demonstrated a mean mitral valve area of 0.7 +/- 0.3 cm2, mean pulmonary artery pressure of 50 +/- 9 mm Hg, and pulmonary artery systolic pressure of 81 +/- 18 mm Hg. Other characteristics included right ventricular failure (18 patients), coronary artery disease (16 patients), and critical aortic stenosis (11 patients). Forty patients underwent mitral valve replacement with St Jude prostheses; 3 had open commissurotomy. Additional surgical procedures included aortic valve replacement (42%), coronary artery bypass graft surgery (26%), and tricuspid valvuloplasty (16%). There were 5 perioperative deaths (11.6%), and 7 other patients (16%) had major complications, including reoperation for hemorrhage, stroke, respiratory failure, myocardial infarction, or a > 30-day hospitalization. Univariate analysis of demographic, hemodynamic, and operative characteristics identified the following predictors of perioperative death (P < .05): acute presentation, clinical evidence of right ventricular failure, impaired left ventricular ejection fraction, and increased left ventricular diastolic pressure. Predictors of complications (P < .05) were acute presentation, ECG evidence of right ventricular hypertrophy, and elevated right ventricular systolic pressure. Multivariate analysis showed only acute presentation and right ventricular hypertrophy as predictors of perioperative death or major complications, respectively. Five- and 10-year actuarial survivals were 80% and 64%, respectively. The only predictor of long-term mortality was advanced age. Functional NYHA status was improved by one grade or more in 76% of survivors. CONCLUSIONS: Patients referred to a tertiary care hospital in the United States with mitral stenosis and severe pulmonary hypertension often have other associated cardiac diseases and comorbid conditions. Cardiac surgery can be successfully performed with an acceptable mortality, and risk factors for poor perioperative outcome can be identified by preoperative clinical characteristics. Younger patients have the best long-term survival, and most survivors experienced long-term improvement in functional status.
Institutional address: University of Pennsylvania Medical Center Philadelphia 19104 USA.
(REFERENCE 70 OF 102) 96017305
Pasque MK Trulock EP Cooper JD Triantafillou AN Huddleston CB Rosenbloom M Sundaresan S Cox JL Patterson GA Single lung transplantation for pulmonary hypertension. Single institution experience in 34 patients.
In: Circulation (1995 Oct 15) 92(8):2252-8
ISSN: 0009-7322
BACKGROUND: The present study considered the uniformity and durability of the cardiopulmonary response to single lung transplantation in patients with severe pulmonary hypertension, as well as its effect on length and quality of survival. METHODS AND RESULTS: Thirty-four patients with pulmonary hypertension underwent evaluation, single lung transplantation, and follow-up assessment between November 1, 1989, and June 1, 1994. Operative survival for the entire group of patients was reasonable, with 91% (31 of 34 patients) surviving and being discharged from the hospital following transplantation. The actuarial survival for these 34 patients at 1-, 2-, and 3-year follow-up was 78%, 66%, and 61%, respectively. In the subgroup of 24 patients with primary pulmonary hypertension (PPH), 96% (23 of 24) were successfully discharged from the hospital after transplantation. The actuarial survival for this isolated PPH subgroup at 1-, 2-, and 3-year follow-up was 87%, 76%, and 68%, respectively. The uniform, early posttransplant normalization of pulmonary vascular resistance and right ventricular ejection fraction appears to persist throughout the 4-year follow-up period. Despite a high prevalence of bronchiolitis obliterans, the majority of survivors remain in New York Heart Association functional class I or II and are employed. CONCLUSIONS: Single lung transplantation can be performed in patients with end-stage pulmonary vascular disease with reasonable expectations for a relatively low operative mortality; immediate, complete, and durable amelioration of pulmonary hypertension and right ventricular failure; and optimal use of limited donor organ supply.
Institutional address: Division of Cardiothoracic Surgery Washington University Medical School St. Louis MO 63110 USA.
(REFERENCE 71 OF 102) 94265329
Petitpretz P Brenot F Azarian R Parent F Rain B Herve P Simonneau G Pulmonary hypertension in patients with human immunodeficiency virus infection. Comparison with primary pulmonary hypertension.
In: Circulation (1994 Jun) 89(6):2722-7
ISSN: 0009-7322
BACKGROUND: Previously reported cases of patients with pulmonary hypertension (PH) and human immunodeficiency virus (HIV) infection are poorly documented regarding baseline hemodynamics and potential for pulmonary vasodilatation. The purpose of this report was to compare HIV-infected patients who had PH with non-HIV-infected patients who had primary pulmonary hypertension (PPH) in terms of (1) clinical characteristics, (2) hemodynamics in baseline conditions and during a short-term vasodilator trial with epoprostenol, and (3) survival. METHODS AND RESULTS: Between April 1987 and August 1992, 20 HIV-infected patients with PH and 93 non-HIV-infected patients with PPH were referred to our department. At the time of referral, baseline right-side heart hemodynamics were obtained in addition to demographic variables and medical history. A short-term vasodilator trial with epoprostenol was performed in 19 of 20 HIV-infected and 86 of 93 non-HIV-infected patients. Outcome and survival were analyzed and compared for both groups (22 transplant recipients were excluded from the group of patients with PPH). At the time of diagnosis of PH, HIV-infected patients significantly differed from non-HIV-infected patients in age (32 +/- 5 versus 42 +/- 13 years; P < .05) and degree of disability (New York Heart Association functional class III or IV, 50% versus 75%; P < .01). The proportion of disease states known to be associated with PPH (Raynaud's phenomenon, migraine, collagen disease without overt symptoms and signs, or a positive family history of PPH) was similar in the two groups. HIV-infected patients had a severe but significantly lower level of PH than patients with PPH. The percentage of responders to epoprostenol and the level achieved in pulmonary vasodilatation were similar in the two groups. PH was the cause of death in 8 of the 10 HIV-infected patients who died within 1 year after the diagnosis of PH. Overall survival was poor and not significantly different between the two groups. Pathological findings in lung tissue obtained from 3 HIV-infected patients were close to those seen in most of the lung specimens available from 27 patients with PPH and resembled plexogenic pulmonary arteriopathy. CONCLUSIONS: These results support the view that HIV infection may now be regarded as another common disease state that can be associated with PPH development. The lower initial severity in HIV-infected patients may be due to the close medical attention usually devoted to such patients, who may account for an earlier diagnosis. However, the overall survival rate of HIV-infected patients with PH appeared to be as poor as in non-HIV-infected patients with PPH.
Institutional address: Hopital Antoine Beclere Clamart France.
(REFERENCE 72 OF 102) 94199739
Sandoval J Bauerle O Palomar A Gomez A Martinez-Guerra ML Beltran M Guerrero ML Survival in primary pulmonary hypertension. Validation of a prognostic equation.
In: Circulation (1994 Apr) 89(4):1733-44
ISSN: 0009-7322
BACKGROUND: The prognosis of patients with primary pulmonary hypertension (PPH) remains a major problem for the planning and assessment of therapeutic interventions. The objectives of this study were (1) to characterize mortality in a Mexican population of patients with PPH and to investigate factors associated with survival and (2) to test the applicability in this population of the prognostic equation proposed by the US National Institutes of Health study on PPH. METHODS AND RESULTS: A dynamic cohort of patients with PPH at our institution were enrolled between June 1977 and August 1991 and prospectively followed at regular intervals through September 1992. Measurements at diagnosis included hemodynamic and pulmonary function variables in addition to information on demographic data and medical history. The response to vasodilator treatment was also analyzed. The estimated median survival of the group was 4.04 years (95% confidence interval, 2.98 to 5.08 years). Variables associated with poor survival (univariate analysis) included an elevated mean right atrial pressure, a decreased cardiac index, and a decreased mixed venous PO2. A reduced forced vital capacity and the absence of vasodilator treatment were also associated with poor survival. A multivariate Cox proportional- hazards regression analysis was used to assess the adjusted hazard ratios, hence the relative contributions of the variables controlling for confounding. Reduced forced vital capacity and cardiac index and increased right atrial pressure were still significantly associated as risk factors for survival in patients with PPH. Survival as computed by the equation correlated with real survival of PPH patients with positive predictive values of 87%, 91%, and 89% at 1, 2, and 3 years, respectively. The equation, however, was relatively unable to predict deaths in our population, in part because of the strict limits of poor prognosis. CONCLUSIONS: Mortality in PPH is largely associated with hemodynamic variables that assess right ventricular function. The proposed prognostic equation had a high sensitivity and a relatively low specificity to predict survival in our PPH population. To improve this specificity it may be necessary to increase the limits of poor prognosis as defined by the equation.
Institutional address: Cardiopulmonary Department Instituto Nacional de Cardiologia Ignacio Chavez Mexico DF Mexico.
(REFERENCE 73 OF 102) 94037352
Wessel DL Adatia I Giglia TM Thompson JE Kulik TJ Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass.
In: Circulation (1993 Nov) 88(5 Pt 1):2128-38
ISSN: 0009-7322
BACKGROUND. Increased pulmonary vascular resistance is common in congenital heart disease and is exacerbated by cardiopulmonary bypass (CPB). We investigated whether CPB is responsible for pulmonary endothelial dysfunction and contributes to postoperative pulmonary hypertension. METHODS AND RESULTS. We infused the endothelium- dependent vasodilator acetylcholine (ACH) into the pulmonary circulation of pulmonary hypertensive children with congenital heart disease either before (n = 12) or after (n = 22) surgical repair on CPB. The dose response to ACH (10(-9) to 10(-6) M) was recorded for all hemodynamic variables. Nine additional postoperative patients were studied with ACH followed by inhalation of 80 ppm nitric oxide, an endothelium-independent smooth muscle relaxant. Plasma levels of cyclic GMP (cGMP) were measured before and after ACH and nitric oxide administration. Pulmonary vasodilation with 10(-6) M ACH was seen in all preoperative patients but was markedly attenuated in postoperative patients. Baseline pulmonary vascular resistance (5.6 +/- 1.0 U x m2) fell 46 +/- 5% in preoperative patients but declined only 11 +/- 4% from baseline (5.8 +/- 0.9 U x m2) in postoperative patients (P < .002). However, inhalation of 80 ppm nitric oxide after ACH infusion in postoperative patients lowered pulmonary vascular resistance by 33 +/- 4% (P < .0002 compared with postoperative ACH response) with minimal effects on the systemic circulation. This finding suggests that the capacity for smooth muscle relaxation and pulmonary vasodilation was present in postoperative patients but could not be induced by ACH. Plasma levels of cGMP in postoperative patients were unchanged after acetylcholine infusion but rose more than threefold during pulmonary vasodilation with nitric oxide (P < .0001). This finding is consistent with the purported role of cGMP as the second messenger effecting smooth muscle relaxation in this process. CONCLUSIONS. CPB may be responsible for postoperative dysfunction of the pulmonary endothelial cell and may contribute to postoperative pulmonary hypertension in children. Inhaled nitric oxide is a potent pulmonary vasodilator after CPB with minimal systemic circulatory effects. It may have important diagnostic and therapeutic applications in patients with congenital heart disease.
Registry Numbers: 10102-43-9 (Nitric Oxide) 51-84-3 (Acetylcholine) 7665-99-8 (Cyclic GMP) 9008-37-1 (Methemoglobin)
Institutional address: Department of Cardiology Children's Hospital Boston MA 02115.
(REFERENCE 74 OF 102) 93121506
Gomez A Unruh H Mink SN Altered left ventricular chamber stiffness and isovolumic relaxation in dogs with chronic pulmonary hypertension caused by emphysema.
In: Circulation (1993 Jan) 87(1):247-60
ISSN: 0009-7322
BACKGROUND. In chronic obstructive lung disease, a right to left ventricular septal shift that occurs as a consequence of right ventricular pressure overload is the usual mechanism given to explain a decrease in left ventricular (LV) diastolic performance. The purpose of the present study was to examine the extent to which this mechanism could account for a decrease in LV diastolic function in a canine model in which pulmonary artery pressure was elevated to a level found in human disease. METHODS AND RESULTS. Severe emphysema was produced in dogs by repeated instillations of the enzyme papain into the lung. To assess LV diastolic function, we used sonomicrometry, in which three pairs of subendocardial crystal transducers were implanted along the three orthogonal axes of the LV. LV end-diastolic dimensions and pressure-strain relations along the three axes, as well as the time constant of LV isovolumic relaxation (T), were measured before (baseline) and after 1 year of emphysema (post-1-year study). The results showed that after 1 year of pulmonary hypertension, LV pressure-strain relations were decreased along the septal-lateral and anterior-posterior axes, but a right to left ventricular septal shift was not detected. The relation of average midwall circumferential stress to midwall circumferential strain was used to describe the intrinsic compliance of the LV. The results showed that myocardial stiffness increased in emphysema but that chamber volume was not reduced. At the post-1-year study, T was abnormally increased in the emphysema group in response to augmented preload and afterload compared with preemphysema measurements. CONCLUSIONS. We conclude that mechanisms other than ventricular interdependence may be operative in leading to altered LV diastolic filling in chronic emphysema.
Registry Numbers: EC 3.4.22.2 (Papain) 59-42-7 (Phenylephrine)
Institutional address: Department of Medicine University of Manitoba Winnipeg Canada.
*****JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY*****
(REFERENCE 75 OF 102) 97303293
Chen EP Bittner HB Tull F Craig D Davis RD Van Trigt P Nitric oxide improves pulmonary vascular impedance, transpulmonary efficiency, and left ventricular filling in chronic pulmonary hypertension.
In: J Thorac Cardiovasc Surg (1997 May) 113(5):849-57
ISSN: 0022-5223
OBJECTIVE: Chronic pulmonary hypertension is difficult to treat and despite the introduction of several therapeutic options, no single therapy is universally recommended. Nitric oxide has had some role clinically in improving pulmonary hemodynamics in this setting; however, basic investigation has not been performed in an appropriate large animal model of stable pulmonary hypertension. This study was designed to examine the effects of inhaled nitric oxide on pulmonary hemodynamics in the setting of a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension and used Fourier analysis for assessment of pulmonary vascular impedance. METHODS: Sixteen mongrel dogs (22 to 25 kg) were used. Animals underwent percutaneous pulmonary artery catheterization to measure-right-sided hemodynamics before and 6 weeks after a right atrial injection of either monocrotaline pyrrole (n = 8) or placebo (n = 8). Six weeks after the injection all hearts were instrumented with an ultrasonic flow probe, sonomicrometric dimension transducers, and micromanometers. Data were collected at baseline and after nitric oxide administration. Harmonic derivation of functional data was achieved with Fourier analysis. RESULTS: Six weeks after the injection, significant increases in pulmonary artery pressure and pulmonary vascular resistance were observed in the monocrotaline pyrrole group. Nitric oxide led to significant decreases in pulmonary vascular impedance. Significant improvements in pulmonary blood flow, transpulmonary efficiency, and left ventricular filling were also observed. CONCLUSIONS: This investigation demonstrates the well-known clinical effects of nitric oxide in improving pulmonary hypertension, which were also associated with an increase in pulmonary blood flow, transpulmonary efficiency, and left ventricular filling in the setting of monocrotaline pyrrole-induced pulmonary hypertension.
Registry Numbers: 23291-96-5 (monocrotaline pyrrole) 315-22-0 (Monocrotaline) 7697-37-2 (Nitric Acid)
Institutional address: Department of Surgery Duke University Medical Center Durham N.C USA.
(REFERENCE 76 OF 102) 97258817
Kirshbom PM Page SO Jacobs MT Tsui SS Bello E Ungerleider RM Schwinn DA Gaynor JW Cardiopulmonary bypass and circulatory arrest increase endothelin-1 production and receptor expression in the lung.
In: J Thorac Cardiovasc Surg (1997 Apr) 113(4):777-83
ISSN: 0022-5223
BACKGROUND: Endothelin-1 has been shown to be a mediator of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest. It is not known whether the mechanism is increased production of endothelin-1 or alterations in expression of endothelin-1 receptors in the lung. This study was designed to test the hypothesis that circulatory arrest increases endothelin-1 mRNA levels and endothelin-1 receptor expression in the lung. METHODS AND RESULTS: Twenty-four piglets (7 to 30 days old) were studied randomly either at baseline (controls, n = 12) or after cardiopulmonary bypass with 30 minutes of circulatory arrest (deep hypothermic circulatory arrest, n = 12). Lungs and pulmonary arteries were harvested immediately after hemodynamic data collection. Deep hypothermic circulatory arrest significantly increased pulmonary vascular resistance (p < 0.01). Deep hypothermic circulatory arrest also produced a significant increase in endothelin-1 mRNA levels in the pulmonary arteries (149 +/- 55 pg vs 547 +/- 111 pg, p = 0.007). There was no significant change in the pulmonary parenchymal endothelin-1 mRNA levels (4102 +/- 379 pg vs 4623 +/- 308 pg, p = 0.32). Ligand binding studies of the lung parenchyma revealed a single specific endothelin-1 binding site with an EC50 value (effective concentration causing 50% of the maximum response) of about 1 x 10(-8) mol/L, consistent with the endothelin B subtype. Deep hypothermic circulatory arrest resulted in a significant increase in the number of endothelin-1 receptors in the lung (109 +/- 6 fmol/mg total protein to 135 +/- 9 fmol/mg total protein, p = 0.02). CONCLUSIONS: Deep hypothermic circulatory arrest increases production of endothelin-1 by the pulmonary vascular endothelium. Endothelin-1 production in the pulmonary parenchyma does not change. Expression of endothelin B receptors in the pulmonary parenchyma also increases after cardiopulmonary bypass with deep hypothermic circulatory arrest. This study supports the hypothesis that deep hypothermic circulatory arrest results in pulmonary vascular endothelial activation with increased endothelin-1 mRNA production.
Institutional address: Department of Surgery Duke University Medical Center Durham N.C. USA.
(REFERENCE 77 OF 102) 97258813
Mishima A Asano M Saito T Yamamoto S Ukai T Yoshitomi H Matsumoto K Manabe T Pulmonary blood flow regulates plasma tissue plasminogen activator concentrations in patients with congenital heart defects.
In: J Thorac Cardiovasc Surg (1997 Apr) 113(4):742-7
ISSN: 0022-5223
OBJECTIVE: The wall shear stress generated by blood flow regulates the expression of fibrinolytic proteins by endothelial cells in vitro. In the present study, the effects of pulmonary blood flow on fibrinolytic activity were studied in patients with congenital heart defects and pulmonary hypertension. METHODS: Twenty-seven patients who underwent cardiac operation because of congenital heart defects were divided into four groups according to the severity of pulmonary hypertension. Group I consisted of seven patients with normal pulmonary artery pressure, group II consisted of nine patients with pulmonary hypertension caused by increased pulmonary blood flow, group III consisted of six patients with pulmonary hypertension caused by increased pulmonary vascular resistance, and group IV consisted of five patients with tetralogy of Fallot. Plasma concentrations of tissue plasminogen activator, plasmin, and thrombin were assayed as the inhibitor-bound forms. RESULTS: The preoperative concentration of tissue plasminogen activator was higher in group II than in all other groups (p = 0.0003). However, the postoperative concentration decreased only in patients in group II when compared with the preoperative value (p = 0.01). By Pearson's correlation analysis, pulmonary blood flow was found to correlate with the preoperative concentration of tissue plasminogen activator (95% confidence interval = 3.99 to 10.58, p = 0.0001). No definite conclusion was found for the relationship between tissue plasminogen activator and plasmin concentration. Further, the preoperative thrombin concentration was similar in all groups. CONCLUSIONS: These findings suggest that pulmonary blood flow may regulate the plasma concentration of tissue plasminogen activator in patients with congenital heart defects.
Registry Numbers: EC 3.4.21.- (Plasminogen Activators) EC 3.4.21.5 (Thrombin) EC 3.4.21.68 (Tissue Plasminogen Activator) EC 3.4.21.7 (Plasmin) EC 3.4.21.- (Alteplase)
Institutional address: First Department of Surgery Nagoya City University Medical School Nagoya Japan.
(REFERENCE 78 OF 102) 97027591
Holm P Liska J Clozel M Franco-Cereceda A The endothelin antagonist bosentan: hemodynamic effects during normoxia and hypoxic pulmonary hypertension in pigs.
In: J Thorac Cardiovasc Surg (1996 Oct) 112(4):890-7
ISSN: 0022-5223
In this study, we investigated the hemodynamic effects and receptor- blocking properties of the nonselective endothelin antagonist bosentan in pigs during normoxia and acute hypoxia. Hypoxic pulmonary hypertension was induced by decreasing the fraction of inhaled oxygen to 0.1. In a control group of pigs, hemodynamic parameters proved to be stable through 2 hours of hypoxia. Infusions of endothelin-1, endothelin-3, and sarafotoxin 6c into the pulmonary artery resulted in pulmonary and systemic vasoconstriction during normoxia, whereas endothelin administration during hypoxic pulmonary hypertension resulted in pulmonary vasodilation. After administration of bosentan, the vasopressor effect of endothelin-1 during normoxia was significantly attenuated and the pulmonary vasodilatory effect of endothelin-1 during hypoxia was reduced. Furthermore, the development of hypoxic pulmonary hypertension was significantly reduced by bosentan. In contrast, bosentan did not influence the pulmonary vasopressor response to the thromboxane mimic U-46619. We therefore conclude that vasopressor endothelin receptors seem to be activated by endogenous endothelin released during hypoxia, leading to an increase in the pulmonary vascular tone.
Registry Numbers: 147536-97-8 (bosentan) 57576-52-0 (Thromboxane A2) 76898-47-0 (15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid) 7782-44-7 (Oxygen)
Institutional address: Department of Thoracic Surgery Karolinska Hospital Stockholm Sweden.
(REFERENCE 79 OF 102) 97478354
Chen JM Levin HR Michler RE Prusmack CJ Rose EA Aaronson KD Reevaluating the significance of pulmonary hypertension before cardiac transplantation: determination of optimal thresholds and quantification of the effect of reversibility on perioperative mortality.
In: J Thorac Cardiovasc Surg (1997 Oct) 114(4):627-34
ISSN: 0022-5223
OBJECTIVES: Right-sided circulatory failure resulting from severe preoperative pulmonary hypertension is a source of mortality early after cardiac transplantation. We undertook the present study (1) to analyze the association of elevated pulmonary hemodynamic indices with 30-day mortality, (2) to define threshold ranges associated with an increase in 30-day mortality, and (3) to evaluate the effect of vasodilator reversibility on 30-day mortality. METHODS: Preoperative hemodynamic profiles were evaluated in 476 patients who ultimately underwent cardiac transplantation. From these data, receiver- operating characteristic curves and stratum-specific likelihood ratios were generated to compare the efficacy of each hemodynamic index. A subset of patients with elevated hemodynamic profiles at baseline additionally underwent graded sodium nitroprusside infusion. RESULTS: Analysis of receiver-operating characteristic curves demonstrated no statistically significant difference among the indices in their ability to predict 30-day mortality. Analysis of stratum-specific likelihood ratios demonstrated three risk strata that correlated with significant differences in 30-day mortality, with patients in the high-risk stratum having a 3.2 to 4.4 increase in odds of 30-day mortality when compared with patients in the low- risk stratum. Nitroprusside data demonstrated that although 30-day mortality was better in patients with reversible pulmonary hypertension than in those with fixed pulmonary hypertension, it was not comparable with that of patients without pulmonary hypertension at baseline. CONCLUSIONS: Candidates for cardiac transplantation may be categorized into three risk strata on the basis of their preoperative pulmonary hemodynamic profile; the association of this profile with 30-day mortality is not linear. Reversibility with nitroprusside appears to confer some improvement in the risk of 30- day mortality, but it may not eliminate the risk entirely.
Registry Numbers: 15078-28-1 (Nitroprusside)
Institutional address: Department of Surgery Columbia University College of Physicians & Surgeons New York N.Y. USA.
(REFERENCE 80 OF 102) 97193039
Fullerton DA Jaggers J Piedalue F Grover FL McIntyre RC Jr Effective control of refractory pulmonary hypertension after cardiac operations.
In: J Thorac Cardiovasc Surg (1997 Feb) 113(2):363-8; discussion 368-70
ISSN: 0022-5223
OBJECTIVES: Inhaled nitric oxide is a promising therapy to control pulmonary hypertension. However, pulmonary hypertension caused by valvular heart disease is often refractory to inhaled nitric oxide. The objective of this study was to determine whether the combination of inhaled nitric oxide plus dipyridamole will cause a response in patients with pulmonary hypertension undergoing cardiac operations who had not responded to inhaled nitric oxide alone. METHODS: Responses in 10 patients (62 +/- 7 years) with pulmonary hypertension caused by aortic or mitral valvular disease (mean pulmonary artery pressure, > or = 30 mm Hg) were studied in the operating room after valve replacement. The effect of inhaled nitric oxide alone (40 ppm) on pulmonary vascular resistance, mean pulmonary artery pressure, cardiac output, and mean arterial pressure was determined. Inhaled nitric oxide administration was then stopped and patients were given dipyridamole (0.2 mg/kg intravenously); the effect of inhaled nitric oxide plus dipyridamole was then examined. RESULTS: Dipyridamole effected a response in patients who had not responded to nitric oxide. Pulmonary vascular resistance and mean pulmonary artery pressure were significantly reduced and cardiac output was increased without change in mean arterial pressure. CONCLUSIONS: Patients with refractory pulmonary hypertension in whom inhaled nitric oxide alone fails to cause a response may respond to combined therapy of inhaled nitric oxide plus dipyridamole. This therapy may be particularly valuable in patients with dysfunction of the right side of the heart as a result of pulmonary hypertension because of its effective lowering of right ventricular afterload.
Registry Numbers: 10102-43-9 (Nitric Oxide) 58-32-2 (Dipyridamole)
Institutional address: Department of Surgery at Northwestern University Chicago Ill. USA.
(REFERENCE 81 OF 102) 95295337
Ikawa S Shimazaki Y Nakano S Kobayashi J Matsuda H Kawashima Y Pulmonary vascular resistance during exercise late after repair of large ventricular septal defects. Relation to age at the time of repair.
In: J Thorac Cardiovasc Surg (1995 Jun) 109(6):1218-24
ISSN: 0022-5223
Postoperative pulmonary artery pressure and resistance were assessed during exercise in 32 patients late after repair of large ventricular septal defect with pulmonary hypertension. Nineteen patients had a preoperative pulmonary-to-systemic resistance ratio of between 0.15 and 0.50 (group 1) and 13 had a ratio between 0.50 and 0.96 (group 2). Age at the time of operation was 0.9 to 13.0 years (4.6 +/- 3.6) in group 1 and 0.8 to 15.8 years (4.3 +/- 4.2) in group 2. Age at the time of restudy was 9 to 21 years (14.5 +/- 3.0) in group 1 and 9 to 22 years (13.5 +/- 4.1) in group 2. Pulmonary artery pressure was measured in the supine position at rest and during exercise, as were the measurements underlying the calculations of pulmonary vascular resistance. Mean pulmonary artery pressure was 13 to 21 mm Hg (17 +/- 2) and 10 to 26 mm Hg (20 +/- 5) in groups 1 and 2, respectively, at rest, and this increased to 17 to 27 mm Hg (22 +/- 3) and 14 to 39 mm Hg (27 +/- 7) in groups 1 and 2, respectively, during exercise (p < 0.05). Pulmonary vascular resistance was 0.51 to 3.40 U.m2 (1.93 +/- 0.63) and 0.79 to 3.31 U.m2 (2.05 +/- 0.65) in groups 1 and 2 at rest. It was 0.58 to 2.24 U.m2 (1.36 +/- 0.57) and 0.81 to 3.85 U.m2 (2.18 +/- 0.97) in groups 1 and 2 during exercise (p < 0.01). Postoperative pulmonary vascular resistance during exercise correlated well with age at the time of repair in both groups (r = 0.65, p < 0.05 in group 1; r = 0.86, p < 0.001 in group 2). These data suggest that 85% of patients with a preoperative pulmonary-to- systemic resistance ratio of between 0.15 and 0.50 would have normal pulmonary vascular resistance during exercise when operated on at younger than 3.8 years old and 85% of those with a preoperative pulmonary-to-systemic resistance ratio of more than 0.50 would have normal pulmonary vascular resistance during exercise when operated on at younger than 1.1 years.
Institutional address: First Department of Surgery Osaka University Medical School Japan.
(REFERENCE 82 OF 102) 95075058
Bando K Armitage JM Paradis IL Keenan RJ Hardesty RL Konishi H Komatsu K Stein KL Shah AN Bahnson HT et al Indications for and results of single, bilateral, and heart-lung transplantation for pulmonary hypertension.
In: J Thorac Cardiovasc Surg (1994 Dec) 108(6):1056-65
ISSN: 0022-5223
The indications for single, bilateral, and heart-lung transplantation for patients with pulmonary hypertension remain controversial. We retrospectively analyzed the results from 11 single, 22 bilateral, and 24 heart-lung transplant procedures performed between January 1989 and January 1993 on 57 consecutive patients with pulmonary hypertension caused by primary pulmonary hypertension (n = 27) or Eisenmenger's syndrome (n = 30). Candidates with a left ventricular ejection fraction less than 35%, coronary artery disease, or Eisenmenger's syndrome caused by surgically irreparable complex congenital heart disease received heart-lung transplantation. All other candidates received single or bilateral lung transplantation according to donor availability. Although postoperative pulmonary artery pressures decreased in all three allograft groups, those in single lung recipients remained significantly higher than those in bilateral and heart-lung recipients. The cardiac index improved significantly in only the bilateral and heart-lung transplant recipients. A significant ventilation/perfusion mismatch occurred in the single lung recipients as compared with bilateral and heart-lung recipients because of preferential blood flow to the allograft. Graft- related mortality was significantly higher and overall functional recovery as assessed by New York Heart Association functional class was significantly lower at 1 year in the single as compared with bilateral and heart-lung recipients. Thus bilateral lung transplantation may be a more satisfactory option for patients with pulmonary hypertension with simple congenital heart disease, absent coronary arterial disease, and preserved left ventricular function. Other candidates will still require heart-lung transplantation.
Institutional address: Division of Cardiothoracic Surgery University of Pittsburgh School of Medicine Pa 15213.
(REFERENCE 83 OF 102) 95057232
Zhu ZG Wang MS Jiang ZB Jiang Z Xu SX Ren CY Shi MX The dynamic change of plasma endothelin-1 during the perioperative period in patients with rheumatic valvular disease and secondary pulmonary hypertension.
In: J Thorac Cardiovasc Surg (1994 Nov) 108(5):960-8
ISSN: 0022-5223
The arterial plasma endothelin-1 concentration was substantially more elevated in 15 patients with rheumatic valvular disease and secondary pulmonary hypertension than in healthy volunteers (3.66 +/- 2.20 versus 1.17 +/- 0.38 pg/ml, mean +/- standard deviation; p < 0.01). The preoperative plasma endothelin-1 level was highly correlated with the pulmonary hemodynamics: pulmonary artery systolic pressure (r = 0.94, p < 0.001), pulmonary artery mean pressure (r = 0.86, p < 0.001), pulmonary capillary wedge pressure (r = 0.82, p < 0.001), and pulmonary vascular resistance (r = 0.63, p < 0.02). After valve replacement, the plasma endothelin-1 concentration declined substantially and the pulmonary hemodynamics improved markedly. Two weeks after the operation, the plasma endothelin-1 level in patients (1.26 +/- 0.45 pg/ml, mean +/- standard deviation) was not statistically different from that in the healthy volunteers. The plasma endothelin-1 concentration continuously increased during the course of cardiopulmonary bypass and peaked after cessation of bypass. The peak plasma endothelin-1 level (13.49 +/- 4.60 pg/ml, mean +/- standard deviation) positively correlated with the bypass time (r = 0.64, p < 0.02) and negatively correlated with the urine volume during bypass (r = -0.69, p < 0.01). We conclude that (1) increased plasma endothelin-1 might be implicated in the pathogenesis of secondary pulmonary hypertension caused by rheumatic valvular disease and (2) markedly elevated plasma endothelin-1 concentrations might be associated with the mechanism of cardiac or renal dysfunction after prolonged cardiopulmonary bypass.
Institutional address: Department of Cardiac Surgery Zhong Shan Hospital Shanghai Medical University Shanghai People's Republic of China.
(REFERENCE 84 OF 102) 98235757
Ivy DD Kinsella JP Ziegler JW Abman SH Dipyridamole attenuates rebound pulmonary hypertension after inhaled nitric oxide withdrawal in postoperative congenital heart disease.
In: J Thorac Cardiovasc Surg (1998 Apr) 115(4):875-82
ISSN: 0022-5223
OBJECTIVE: Inhaled nitric oxide therapy causes selective and sustained pulmonary vasodilation in patients with pulmonary hypertension; however, attempts to discontinue inhaled nitric oxide therapy may be complicated by abrupt life-threatening events. Dipyridamole, a cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, blocks the hydrolysis of cyclic guanosine monophosphate in vascular smooth muscle cells. METHODS: We studied 23 consecutive children who were treated with inhaled nitric oxide because of clinically significant pulmonary hypertension after surgery for congenital heart disease. Inhaled nitric oxide therapy was withdrawn before and after dipyridamole treatment of children in whom sustained elevations of pulmonary artery pressure developed for over 30 minutes. RESULTS: In 7 of 23 children, inhaled nitric oxide withdrawal caused a 40% increase in pulmonary artery pressure, a 17% decrease in systemic venous oxygen saturation, and a 46% increase in the ratio of mean pulmonary artery pressure to aortic pressure. Compared with children who had no significant increase in pulmonary artery pressure, children who experienced the development of prolonged pulmonary hypertension after inhaled nitric oxide therapy withdrawal had higher mean pulmonary artery pressure immediately before inhaled nitric oxide withdrawal (22 +/- 1 mm Hg versus 27 +/- 2 mm Hg; p = 0.04) and received inhaled nitric oxide for a longer duration (2 +/- 1 days versus 4 +/- 1 days; p = 0.01). Dipyridamole therapy attenuated the rise in pulmonary artery pressure and fall in systemic venous oxygen saturation in all six patients studied with rebound pulmonary hypertension after withdrawal of inhaled nitric oxide. CONCLUSION: We conclude that dipyridamole therapy acutely attenuates the adverse hemodynamic effects of rapid withdrawal of inhaled nitric oxide therapy. Children with higher pulmonary artery pressure and who are treated with inhaled nitric oxide for a longer duration may be at increased risk for adverse hemodynamic effects of inhaled nitric oxide therapy withdrawal. We speculate that dipyridamole therapy may sustain elevations of smooth muscle cyclic guanosine monophosphate induced by inhaled nitric oxide and that phosphodiesterase activity contributes to acute pulmonary hypertension after inhaled nitric oxide withdrawal.
Registry Numbers: EC 3.1.4.35 (3',5'-Cyclic-GMP Phosphodiesterase) 10102-43-9 (Nitric Oxide) 58-32-2 (Dipyridamole)
Institutional address: Pediatric Heart Lung Center Department of Pediatrics University of Colorado School of Medicine & The Children's Hospital Denver 80218 USA.
(REFERENCE 85 OF 102) 98195136
Argenziano M Dean DA Moazami N Goldstein DJ Rose EA Spotnitz HM Burkhoff D Oz MC Dickstein ML Inhaled nitric oxide is not a myocardial depressant in a porcine model of heart failure [see comments]
In: J Thorac Cardiovasc Surg (1998 Mar) 115(3):700-8
ISSN: 0022-5223
BACKGROUND: Inhaled nitric oxide has been shown to be a potent and selective pulmonary vasodilator. Reports of increases in left ventricular end-diastolic pressure and episodes of pulmonary edema during the clinical use of inhaled nitric oxide in patients with preexisting left ventricular dysfunction have raised concerns that this agent may have myocardial depressant effects. We therefore undertook a study of the effects of inhaled nitric oxide on myocardial contractility in a porcine model of ventricular failure and pulmonary hypertension. METHODS: After inducing heart failure in 10 pigs by rapid ventricular pacing, hemodynamic measurements and pressure-volume diagrams (by the conductance method) were obtained in six animals at baseline and during administration of inhaled nitric oxide at concentrations of 20 and 40 ppm. Myocardial contractile state was assessed by the end-systolic pressure-volume relationship and preload-recruitable stroke work, whereas diastolic function was measured in terms of the end-diastolic pressure-volume relationship and the pressure decay time constant T. RESULTS: Baseline hemodynamics reflected heart failure and pulmonary hypertension, and inhaled nitric oxide induced significant reductions in mean pulmonary artery pressure and pulmonary vascular resistance. Although left ventricular end-diastolic pressure increased during administration of inhaled nitric oxide, no changes were observed in measures of systolic or diastolic function. CONCLUSIONS: Inhaled nitric oxide reduced pulmonary vascular resistance but did not alter myocardial contractility or diastolic function. Increases in left ventricular end-diastolic pressure during inhaled nitric oxide therapy are therefore not due to myocardial depression and may be related to increases in volume delivery to the left side of the heart resulting from reduced pulmonary vascular resistance.
Comment in: J Thorac Cardiovasc Surg 1999 Jan;117(1):195-6
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Division of Cardiothoracic Surgery Columbia University College of Physicians and Surgeons New York NY USA.
(REFERENCE 86 OF 102) 98195114
Bando K Vijay P Turrentine MW Sharp TG Means LJ Ensing GJ Lalone BJ Sekine Y Szekely L Brown JW Dilutional and modified ultrafiltration reduces pulmonary hypertension after operations for congenital heart disease: a prospective randomized study.
In: J Thorac Cardiovasc Surg (1998 Mar) 115(3):517-25; discussion 525-7
ISSN: 0022-5223
OBJECTIVE: A prospective randomized study was performed to test whether removal of endothelin-1, by ultrafiltration techniques, will reduce pulmonary hypertension after operations for congenital heart disease. METHODS: Twenty-four patients with pulmonary hypertension (systolic pulmonary/systemic arterial pressure ratio > 60%) undergoing cardiac operations were randomized into a control group (n = 12) having conventional ultrafiltration and an experimental group (n = 12) undergoing dilutional ultrafiltration during and modified ultrafiltration after cardiopulmonary bypass. Plasma endothelin-1, nitric oxide metabolites, and cyclic guanosine monophosphate were assayed before bypass, 10 minutes into bypass, after bypass, and 0, 3, 6, and 12 hours after the operation in both groups, as well as in the ultrafiltrates and after modified ultrafiltration in the experimental group. Both groups received alpha-blockers (chlorpromazine and/or prazosin) postoperatively using the same guidelines. RESULTS: The ultrafiltrates contained significant amounts of endothelin-1 (1.81 +/- 0.86 pg/ml, dilutional, and 6.44 +/- 1.82 pg/ml, modified ultrafiltrate). Endothelin-1 and the pulmonary/systemic pressure ratio were significantly lower in experimental compared with control patients. Nitric oxide metabolites and cyclic guanosine monophosphate increased similarly in both groups for 12 hours after the operation (p = not significant). Three of 12 control patients (25%) but no experimental patients had pulmonary hypertensive crises (p = 0.07). The experimental patients required significantly less ventilatory support (67 +/- 47 hours vs 178 +/- 139 hours for control patients, p = 0.048). CONCLUSIONS: Dilutional and modified ultrafiltration reduce endothelin-1 and the pulmonary/systemic pressure ratio postoperatively and may become an important adjunct for preventing pulmonary hypertension after operations for congenital heart disease in high-risk patients.
Registry Numbers: 10024-97-2 (Nitrous Oxide) 7665-99-8 (Cyclic GMP)
Institutional address: Section of Cardiothoracic Surgery James W. Riley Hospital for Children and Indiana University Medical Center Indianapolis 46202-5123 USA.
(REFERENCE 87 OF 102) 98133682
Gammie JS Keenan RJ Pham SM McGrath MF Hattler BG Khoshbin E Griffith BP Single- versus double-lung transplantation for pulmonary hypertension [published erratum appears in J Thorac Cardiovasc Surg 1998 Mar;115(3):731] [see comments]
In: J Thorac Cardiovasc Surg (1998 Feb) 115(2):397-402; discussion 402-3
ISSN: 0022-5223
OBJECTIVES: Uncertainty persists as to the best lung transplant operation for patients with pulmonary hypertension. To quantify short- and long-term outcomes after single- and double-lung transplantation for pulmonary hypertension, we reviewed our clinical experience. METHODS: A retrospective review of 58 lung transplants at a single institution between 1989 and 1996 was performed. Recipients had primary (n = 19) or secondary (n = 39) pulmonary hypertension. RESULTS: Thirty-seven double- and 21 single-lung transplants were performed. The groups were well matched with regard to preoperative characteristics. Cardiopulmonary bypass time was longer (151 vs 250 minutes) in the double-lung group. Excluding 10 patients surviving less than 30 days (6 double- and 4 single-lung transplants), median duration of intubation (7.5 vs 10 days), length of stay in the intensive care unit (10 vs 16 days), and hospital stay (32 vs 52 days) were not significantly different for the single- and double- lung groups, respectively. Actuarial survival was nearly identical, with 81% and 84% 1-month survivals for the single- and double-lung groups, and identical 1-year (67%) and 4-year (57%) survivals for both groups. Late functional status was similar for recipients of single- and double-lung grafts. During the period of this study, 58 patients with pulmonary hypertension died on our center's waiting list before coming to transplantation. CONCLUSIONS: These data suggest that lung transplant recipients with pulmonary hypertension have similar outcomes after single- or double-lung transplantation. These results support cautious preferential application of single- lung transplantation for pulmonary hypertension.
Comment in: J Thorac Cardiovasc Surg 1999 Feb;117(2):404-5
Institutional address: Division of Cardiothoracic Surgery University of Pittsburgh Medical Center Pa 15213 USA.
(REFERENCE 88 OF 102) 98133676
Scarborough JE Daggett CW Lodge AJ Chai PJ Williamson JA Jaggers J George SE Ungerleider RM The role of endothelial nitric oxide synthase expression in the development of pulmonary hypertension in chronically hypoxic infant swine.
In: J Thorac Cardiovasc Surg (1998 Feb) 115(2):343-8; discussion 348-50
ISSN: 0022-5223
OBJECTIVE: Our goal was to determine the role of pulmonary endothelial nitric oxide synthase expression in the development of pulmonary hypertension in infants with congenital cyanotic heart disease. METHODS: Two groups of 4-week-old piglets were studied. In one group, the piglets were raised in an environment of 10% oxygen from 2 days of age (cyanotic, n = 6), and in the other group the piglets were raised at room air (control, n = 5). Pulmonary hemodynamics were measured in vivo for each animal, and peripheral lung biopsy specimens were obtained for Western blot analysis with the use of antiendothelial nitric oxide synthase antibody and for activity analysis with the use of the tritiated L-arginine assay. RESULTS: The piglets in the chronically hypoxic group had significant increases in mean pulmonary arterial pressure (44.0 +/- 3.8 mm Hg vs 14.8 +/- 1.2 mm Hg in controls, p = 0.0007) and pulmonary vascular resistance (7272.0 +/- 871.1 dyne x cm x sec(-5) vs 1844.5 +/- 271.2 dyne x cm x sec(-5) in controls, p = 0.002). These changes in the pulmonary hemodynamics of the hypoxic piglets were accompanied by a twofold increase in the expression of pulmonary endothelial nitric oxide synthase (p = 0.0043) but no corresponding increase in nitric oxide synthase activity. CONCLUSIONS: Raising infant piglets in an environment of 10% oxygen for 4 weeks results in significant pulmonary arterial hypertension accompanied by increased expression of nitric oxide synthase within the lung endothelium. Furthermore, the increased levels of nitric oxide synthase within the lungs of the hypoxic swine were not accompanied by a proportional increase in enzyme activity. These findings suggest that the development of pulmonary hypertension in infants with congenital cyanotic disease is not due to decreased expression of endothelial nitric oxide synthase, but instead may be related to a decreased ability of the enzyme to produce sufficient nitric oxide.
Registry Numbers: EC 1.14.13.39 (Nitric-Oxide Synthase)
Institutional address: Department of Surgery Duke University Medical Center Durham NC 27710 USA.
(REFERENCE 89 OF 102) 98096299
Starnes VA Barr ML Schenkel FA Horn MV Cohen RG Hagen JA Wells WJ Experience with living-donor lobar transplantation for indications other than cystic fibrosis.
In: J Thorac Cardiovasc Surg (1997 Dec) 114(6):917-21; discussion 921-2
ISSN: 0022-5223
OBJECTIVE: Since development of a living donor bilateral lobar transplantation protocol for patients with cystic fibrosis, our indications have expanded to include recipients with other diagnoses. METHODS: We report on our experience in eight patients with primary pulmonary hypertension, postchemotherapy pulmonary fibrosis, bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and obliterative bronchiolitis. The average age of the eight patients was 19.1 years (range 9 to 40). The mean preoperative carbon dioxide tension for the four patients who did not have primary pulmonary hypertension was 92 mm Hg (range 64 to 120 mm Hg), and the two patients with pulmonary fibrosis were intubated (one on high- frequency jet ventilation). Each recipient received a right lower lobe (n = 7) or middle lobe (n = 1) and a left lower lobe (n = 8) from a total of 16 donors representing various combinations of the recipient's family (n = 15) and an unrelated friend (n = 1). RESULTS: With an average follow-up of 1 year the overall survival is 75%. For the five patients followed up for at least 1 year, mean forced vital capacity was 80.6%, forced expiratory volume in 1 second was 75.6%, mid-forced expiratory flow was 64%, and diffusing lung capacity corrected for alveolar volume was 73% of predicted. For those patients with primary pulmonary hypertension, preoperative hemodynamics revealed mean pressures as follows: blood pressure 84.8 mm Hg, right atrial pressure 7.8 mm Hg, pulmonary artery pressure 71.3 mm Hg, pulmonary capillary wedge pressure 9.5 mm Hg, cardiac index 2.9 L/min per square meter, and pulmonary vascular resistance index 22.8 Wood units. Postoperative hemodynamics revealed a mean blood pressure of 84.3 mm Hg, right atrial pressure of 2.7 mm Hg, pulmonary artery pressure of 16 mm Hg, pulmonary capillary wedge pressure of 7.3 mm Hg, cardiac index of 4.2 L/min per square meter, and pulmonary vascular resistance index of 1.9 Wood units. CONCLUSIONS: Early results of living-donor bilateral lobar transplantation for diseases other than cystic fibrosis have resulted in satisfactory survival and pulmonary function. Additionally, patients with severe primary pulmonary hypertension have had dramatic normalization of their hemodynamics despite the limited amount of lung tissue transplanted. We believe that the data from this small cohort experience compares favorably with our larger series with cystic fibrosis and supports an expanded role for living-donor lobar transplantation in patients with alternate indications.
Institutional address: Division of Cardiothoracic Surgery University of Southern California Los Angeles USA.
(REFERENCE 90 OF 102) 96350099
Waldenberger F Kim YI Laycock S Meyns B Flameng W Effects of failure of the right side of the heart and increased pulmonary resistance on mechanical circulatory support with use of the miniaturized HIA-VAD displacement pump system.
In: J Thorac Cardiovasc Surg (1996 Aug) 112(2):484-93
ISSN: 0022-5223
This experimental study was designed to assess the influence of failure of the right side of the heart or pulmonary hypertension, or both, on the performance of a novel miniaturized left ventricular assist device. In small-sized dogs (n = 50) ischemic global left ventricular failure was induced and support was provided by the HIA- VAD displacement pump (stroke volume 10 or 25 ml) installed as a left ventricular assist device. In three groups of animals (n = 10 each) pulmonary hypertension was created before induction of global left ventricular failure. During left ventricular assist device support temporary ischemic failure of the right side of the heart was induced in four groups of animals (n = 10 each). In the group subjected to left ventricular failure, support with the left ventricular assist device, and right ventricular failure during left ventricular assist, left atrial pressure and cardiac index were significantly lower than in the group subjected to left ventricular failure and left ventricular assist alone (2 +/- 6 versus 11 +/- 6 mm Hg and 1.6 +/- 0.4 versus 1.0 +/- 0.4 L/(min/m2), respectively, p < 0.05). In the group subjected to pulmonary hypertension, left ventricular failure, and left ventricular support, left atrial pressure dropped to values near zero but cardiac index remained unaltered as compared with results with the same regimen without pulmonary hypertension. However, when right ventricular failure was added (that is, pulmonary hypertension, left ventricular failure, left ventricular support, and right ventricular failure during support with the left ventricular assist device) left atrial pressure dropped to negative values (p < 0.05) and cardiac index progressively deteriorated. When, in an additional group of dogs, biventricular support was installed in the latter regimen, circulation was initially well supported but oxygenation deteriorated in 60% of cases. We conclude that (1) adequate right ventricular function was indispensable during support with the left ventricular assist device, (2) the combination of pulmonary hypertension and right ventricular failure led to the "low left ventricular assist device output syndrome," and (3) biventricular mechanical support in the presence of pulmonary hypertension may be complicated by the alveolar leakage syndrome.
Registry Numbers: 7782-44-7 (Oxygen)
Institutional address: Department of Cardiac Surgery Katholieke Universiteit Leuven Belgium.
(REFERENCE 91 OF 102) 97450212
Goldstein DJ Dean DA Smerling A Oz MC Burkhoff D Dickstein ML Inhaled nitric oxide is not a negative inotropic agent in a porcine model of pulmonary hypertension.
In: J Thorac Cardiovasc Surg (1997 Sep) 114(3):461-6
ISSN: 0022-5223
BACKGROUND: Reports of pulmonary edema complicating inhaled nitric oxide therapy in patients with chronic heart failure and pulmonary hypertension have raised the concern that inhaled nitric oxide may have negative inotropic effects. METHODS AND RESULTS: We investigated the effect of multiple doses of inhaled nitric oxide (20, 40 and 80 ppm) on left ventricular contractile state in 10 open-chest pigs. Pressure-volume loops were generated during transient preload reduction to determine the end-systolic pressure-volume relationship and the stroke work-end-diastolic volume relation. Inhaled nitric oxide had no effect on systemic vascular resistance, cardiac output, end-systolic pressure volume relationship or stroke work-end- diastolic volume relation under normal conditions. After induction of pulmonary hypertension (intravenous thromboxane A2 analog), inhalation of nitric oxide (80 ppm) resulted in a reduction in pulmonary vascular resistance (mean +/- standard error of the mean) from 10.4 +/- 3 to 6.5 +/- 2 Wood units (p < 0.001) and in pulmonary artery pressure from 44 +/- 4 to 33 +/- 4 mm Hg (p < 0.05). Left ventricular end-diastolic volume rose from 53 +/- 9 ml to 57 +/- 10 ml (p = 0.02). No statistically significant change in cardiac output or systemic vascular resistance was observed. Inhaled nitric oxide had no effect on end-systolic pressure-volume relationship or stroke work-end-diastolic volume relation. CONCLUSIONS: In a porcine model of pulmonary hypertension, inhaled nitric oxide does not impair left ventricular contractile function. Therefore the cause of pulmonary edema observed in some patients receiving inhaled nitric oxide is not due to a negative inotropic action of this therapy.
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Department of Surgery College of Physicians and Surgeons Columbia University New York N.Y. USA.
(REFERENCE 92 OF 102) 97129976
Bando K Turrentine MW Sharp TG Sekine Y Aufiero TX Sun K Sekine E Brown JW Pulmonary hypertension after operations for congenital heart disease: analysis of risk factors and management.
In: J Thorac Cardiovasc Surg (1996 Dec) 112(6):1600-7; discussion 1607-9
ISSN: 0022-5223
BACKGROUND: Management of pulmonary hypertension, a potentially fatal complication of operations to correct congenital heart disease, has evolved through the last 15 years. Monitoring of pulmonary arterial pressure and mixed venous saturation became available, and prophylactic use of alpha-blockers and other vasodilators increased. This study examines risk factors for morbidity and mortality from pulmonary hypertension after operations to correct congenital heart disease and evaluates the impact of management changes on outcomes. METHODS: By means of multivariable logistic regression analysis, 880 high-risk patients with congenital heart disease (of 2484 patients undergoing cardiopulmonary bypass between January 1980 and December 1994) were analyzed to determine which were at risk for postoperative pulmonary hypertension and its associated morbidity and mortality. RESULTS: Patients with atrioventricular canal (n = 182), truncus arteriosus (n = 47), total anomalous pulmonary venous connection (n = 90), transposition of great arteries (n = 97), hypoplastic left heart syndrome (n = 50), and ventricular septal defect (n = 414) demonstrated a higher risk of postoperative pulmonary hypertension. By multivariable logistic regression, preoperative pulmonary hypertension (p < 0.0001), absence of mixed venous saturation monitoring (p < 0.0001), and absence of prophylactic alpha-blockade (p = 0.0004) significantly increased postoperative pulmonary hypertension. Preoperative pulmonary hypertension (p < 0.001) and absence of prophylactic alpha-blockers (p = 0.0004) were significant risk factors for in-hospital death related to pulmonary hypertension. Repair at older age (except in the case of total anomalous pulmonary venous connection) was a significant risk for postoperative pulmonary hypertension (p = 0.03). CONCLUSION: Mixed venous saturation monitoring and alpha-receptor blockade reduced the incidence of pulmonary hypertension after operations for congenital heart disease. Early definitive repair reduced morbidity and mortality from postoperative pulmonary hypertension.
Institutional address: Section of Cardiothoracic Surgery James W. Riley Hospital for Children and Indiana University Medical Center Indianapolis 46202-5123 USA.
(REFERENCE 93 OF 102) 94210938
Fukushima N Gundry SR Razzouk AJ Bailey LL Risk factors for graft failure associated with pulmonary hypertension after pediatric heart transplantation.
In: J Thorac Cardiovasc Surg (1994 Apr) 107(4):985-9
ISSN: 0022-5223
Postoperative pulmonary hypertension can be a major cause of early death after heart transplantation in children. To identify predictive risk factors of pulmonary hypertension after heart transplantation, we performed a retrospective analysis of our 194 infant and pediatric recipients who underwent heart transplantation between 1987 and 1992. Because the response of pulmonary vasculature may change during growth, the patients were divided into two groups: age less than 1 year in group I (n = 152) and 1 year or older in group C (n = 43). The following risk factors were evaluated: cardiomyopathy, congenital heart disease and hypoplastic left heart syndrome, pretransplant pulmonary hypertension, history of operation, oversized donor (donor/recipient weight ratio greater than 2), donor's history of cardiopulmonary resuscitation, and prolonged graft ischemic time (graft ischemic time 360 minutes or longer). Though there was no significant difference between group I and group C in overall early mortality including early graft loss (19 of 152 versus 5 of 42), the mortality rate from pulmonary hypertension in group I was significantly lower than that in group C (2 of 152 versus 4 of 42; p < 0.05). The mortality rate from pulmonary hypertension in patients with congenital heart disease in group I was significantly lower than that in group C (0 of 44 versus 4 of 24; p < 0.05). In group I, there was no significant difference in the early mortality rate or the mortality rate from pulmonary hypertension from any factors studied. The mortality rate from pulmonary hypertension in association with prolonged graft ischemic time in group C was significantly higher than when no prolonged graft ischemic time was present in group C and with either prolonged graft ischemic time or no prolonged graft ischemic time in group I (4 of 16 versus 0 of 26, 0 of 37, and 2 of 115). In conclusion, older patients had a higher mortality rate from pulmonary hypertension after heart transplantation, especially in patients with congenital heart disease who received a graft preserved more than 6 hours. This study demonstrates another benefit of early heart transplantation in infancy, that is, prevention of death from pulmonary hypertension.
Institutional address: Loma Linda University Medical Center Department of Surgery CA 92354.
(REFERENCE 94 OF 102) 94210921
Journois D Pouard P Mauriat P Malhere T Vouhe P Safran D Inhaled nitric oxide as a therapy for pulmonary hypertension after operations for congenital heart defects.
In: J Thorac Cardiovasc Surg (1994 Apr) 107(4):1129-35
ISSN: 0022-5223
Seventeen infants were treated with inhaled nitric oxide for critical pulmonary artery hypertension after operations for congenital heart defects. In all 17 patients conventional medical therapy consisting of hyperventilation, deep sedation/analgesia, and correction of metabolic acidosis had failed. All children were monitored with a transthoracic pulmonary artery catheter inserted at operation. Pulmonary artery hypertension was defined as an acute rise in pulmonary pressure associated with a decrease in oxygen arterial or venous saturation. After failure of conventional medical therapy, 20 ppm of inhaled nitric oxide was administered to the patient. In all patients the pulmonary pressures decreased (mean pulmonary arterial pressure decreased by -34% +/- 21%) without significant change in systemic arterial pressure, whereas the oxygen arterial saturation and oxygen venous saturation increased by 9.7% +/- 12% and 37% +/- 28%, respectively. Fifteen children were discharged from the intensive care unit at 10 +/- 6 days (range 3 to 26 days) and two died. This study demonstrates that inhaled nitric oxide exerts a selective pulmonary vasodilation without decreasing systemic arterial pressure in children with congenital heart disease. The increased values of mixed venous oxygen saturation and urinary output suggest that this selective lowering of pulmonary vascular resistance improved the overall hemodynamics. The potential toxic effects of nitric oxide and nitrogen dioxide necessitate careful consideration of the risks and benefits of inhaled nitric oxide therapy.
Registry Numbers: 10102-43-9 (Nitric Oxide)
Institutional address: Department of Anesthesia and Intensive Care Medicine Hopital Laennec Paris France.
(REFERENCE 95 OF 102) 94173047
Smith WJ Murphy MP Appleyard RF Rizzo RJ Aklog L Laurence RG Cohn LH Prevention of complement-induced pulmonary hypertension and improvement of right ventricular function by selective thromboxane receptor antagonism.
In: J Thorac Cardiovasc Surg (1994 Mar) 107(3):800-6
ISSN: 0022-5223
The effect of complement activation on the pulmonary vascular system and on right ventricular function was studied in sheep (n = 12) by injection of cobra venom factor. Animals were instrumented for measurement of pulmonary flow, mean pulmonary artery pressure, right ventricular stroke work, arterial blood gases, and systemic vascular resistance. Blood was sampled from the left atrium and pulmonary artery to measure thromboxane B2, the metabolite of thromboxane A2, by radioimmunoassay. After baseline measurements, animals were randomly assigned to receive a selective thromboxane receptor antagonist SQ30741 as a 10 mg/kg bolus with an infusion of 10 mg/kg per hour or else to receive vehicle. Cobra venom factor was then injected (30 U/kg) in all animals, and data were recorded at 15, 30, 60, 90, and 120 minutes. In control animals there was a 2.4-fold increase in mean pulmonary artery pressure and a 76% increase in right ventricular stroke work at 15 minutes from baseline (p < 0.05); these values remained elevated for 30 minutes and returned to baseline by 1 hour with no change in systemic vascular resistance. Arterial oxygenation decreased by 124% at 15 minutes and remained depressed through the experiment, but in treated animals oxygen tension remained unchanged from baseline. Thromboxane B2 increased 95% from baseline in the control group and 1.5 fold in treated animals and followed a similar time course as the functional measurements (p < 0.05). A pulmonary vascular thromboxane B2 gradient of approximately 1000 pg/ml was measured at 15 and 30 minutes in both control and treated groups. (p < 0.05) We conclude that after complement activation in this model pulmonary hypertension and decreased oxygen tension are mediated by thromboxane release from the pulmonary vascular bed. This increased afterload causes a stress on the right ventricle as demonstrated by the increased right ventricular stroke work. Selective thromboxane receptor antagonism may be a beneficial therapy for pulmonary hypertension in patients after cardiopulmonary bypass.
Registry Numbers: 107332-47-8 (SQ 30741) 54397-85-2 (Thromboxane B2) 57576-52-0 (Thromboxane A2) 7782-44-7 (Oxygen)
Institutional address: Division of Cardiac Surgery Brigham and Women's Hospital Boston MA 02115.
(REFERENCE 96 OF 102) 94066530
Cave AC Manche A Derias NW Hearse DJ Thromboxane A2 mediates pulmonary hypertension after cardiopulmonary bypass in the rabbit.
In: J Thorac Cardiovasc Surg (1993 Dec) 106(6):959-67
ISSN: 0022-5223
Clinically, it is well established that cardiopulmonary bypass results in pulmonary dysfunction. Using a recently developed preparation for cardiopulmonary bypass in the rabbit, we have been able to mimic a similar, but more severe, condition. We found that, despite normal histologic structure of the myocardium, hearts could not be weaned from bypass because of a serious increase in pulmonary vascular resistance. Histologic studies of the lungs showed severe intravascular neutrophil aggregation and marked vasoconstriction. To identify the nature and origin of the mediator responsible for the changes in the pulmonary vasculature, we subjected groups of rabbits (n = 4 per group) to bypass with cooling to 18 degrees C, circulatory arrest for 1 hour, and rewarming on bypass to 33 degrees C. Pulmonary vascular resistance was measured at the same temperature before and after bypass. Four groups were studied: group I were untreated controls; group II received the cyclooxygenase inhibitor, indomethacin (0.2 mg/kg intravenously), before operation; group III received the thromboxane A2 synthetase inhibitor, Dazmegral (5 mg/kg intravenously), before operation together with the thromboxane A2 receptor blocker GR 32191B (2 mg/kg per 30 minutes intravenously); and group IV were treated with mustine hydrochloride (1.75 mg/kg intravenously) 3 days before the experiment to deplete the neutrophils by 90%. During circulatory arrest, the heart was protected with an initial infusion (10 ml at 4 degrees C over 1 minute) of St. Thomas' Hospital cardioplegic solution. At the end of the experiment, the heart and lungs were histologically examined. In the control group, a significant increase (+395% when compared with the value recorded before bypass) in pulmonary vascular resistance was observed after bypass. However, in none of the treated groups did pulmonary vascular resistance increase significantly (percentage changes in groups II, III, and IV were -24%, 0%, and +33%, respectively). Pulmonary histologic characteristics were normal in all treated groups, and all animals were successfully weaned from bypass. These results indicate that the increase in pulmonary vascular resistance that arises as a consequence of bypass in rabbits is primarily a result of the production of thromboxane A2, a process in which the neutrophil plays a pivotal role.
Registry Numbers: 57576-52-0 (Thromboxane A2)
Institutional address: Department of Cardiovascular Research Rayne Institute St. Thomas' Hospital London England.
(REFERENCE 97 OF 102) 94066493
Kawaguchi AT Kawashima Y Ishibashi-Ueda H Yanase M Murakami T Yagihara T Kunieda T Right-to-left interatrial shunt in rats with progressive pulmonary hypertension.
In: J Thorac Cardiovasc Surg (1993 Dec) 106(6):1072-80
ISSN: 0022-5223
A right-to-left interatrial shunt may prolong survival in patients with pulmonary hypertension presumably because of decompression of the right side of the heart. To test this hypothesis, 74 rats with monocrotaline-induced pulmonary hypertension were followed up weekly with cardiopulmonary exercise testing with a metabolic treadmill system for exercise tolerance, heart rate, oxygen uptake, carbon dioxide production, and survival until subsequent or induced death 8 weeks after monocrotaline treatment. In rats with an interatrial shunt, oxygen uptake and carbon dioxide production were higher and survival was better (n = 22, 27%) than those in rats without a shunt (n = 52, 0%; p < 0.05). For the prospective assessment of the effects of a reversed shunt, 24 other rats underwent a left superior vena cava-to-left atrial appendage anastomosis as a functional interatrial shunt (atrial septal defect group) 4 weeks after monocrotaline treatment when severe pulmonary hypertension had developed and were compared with an additional 25 rats receiving a sham operation. Both groups had exercise capacity depressed to the resting levels by 2 weeks after operation. Although transcutaneous oxygen levels decreased in response to exercise in the atrial septal defect group, uptake and carbon dioxide production stayed higher than those in the sham operation group with significantly better survival 4 weeks after operation (atrial septal defect 30% versus sham operation, 0%; p < 0.05), at which time a reversed shunt was determined with systemic embolization of intravenously infused microspheres. A right-to-left interatrial shunt, anatomic or functional, preserved basal metabolism and prolonged survival in rats with progressive pulmonary hypertension.
Registry Numbers: 315-22-0 (Monocrotaline)
Institutional address: Department of Cardiovascular Surgery Osaka University School of Medicine Japan.
(REFERENCE 98 OF 102) 93368158
Komai H Adatia IT Elliott MJ de Leval MR Haworth SG Increased plasma levels of endothelin-1 after cardiopulmonary bypass in patients with pulmonary hypertension and congenital heart disease.
In: J Thorac Cardiovasc Surg (1993 Sep) 106(3):473-8
ISSN: 0022-5223
The plasma level of the potent vasoconstrictor endothelin-1 was measured in children who underwent cardiac operations. Forty-five patients were divided into two groups, those with a high pulmonary blood flow (HF group; n = 23) and those with a normal or low flow (NF group; n = 22). Seven blood samples were taken: immediately before cardiopulmonary bypass, immediately after removing the aortic cross- clamps, immediately after discontinuing bypass, and at 20 minutes and 3, 6, and 24 hours after termination of bypass. The plasma levels of endothelin-1 were similar in both groups before bypass. From the time the aortic crossclamps were removed, the plasma endothelin-1 levels in both groups increased significantly, to reach a peak level at 3 to 6 hours. The increase was significantly greater in the HF than in the NF group, and the maximum values in the two groups were 12.6 +/- 1.1 and 9.6 +/- 0.8 fmol/ml, respectively (mean +/- standard error of the mean, p < 0.05). The value 20 minutes after bypass showed a positive correlation with the mean pulmonary arterial pressure measured at the preoperative cardiac catheterization study (r = 0.41, p < 0.05). In addition, a significant positive correlation was obtained between endothelin-1 3 hours after bypass and the maximum pulmonary/systemic arterial pressure ratio during the first 12 hours after operation (r = 0.86, p < 0.05). These results suggest that cardiopulmonary bypass is associated with an immediate postoperative increase in circulating endothelin and that patients who had a high pulmonary blood flow before the operation are particularly vulnerable, bypass having a more injurious effect on a lung with preexisting endothelial dysfunction. A high level of circulating endothelin may predispose to pulmonary vascular lability and pulmonary hypertensive crises in the postoperative period.
Institutional address: Vascular Biology and Pharmacology Unit Institute of Child Health London England.
(REFERENCE 99 OF 102) 93368147
Yamaki S Yasui H Kado H Yonenaga K Nakamura Y Kikuchi T Ajiki H Tsunemoto M Mohri H Pulmonary vascular disease and operative indications in complete atrioventricular canal defect in early infancy.
In: J Thorac Cardiovasc Surg (1993 Sep) 106(3):398-405
ISSN: 0022-5223
Pulmonary vascular disease was morphometrically analyzed in 67 patients (mean age, 19 months) with isolated complete atrioventricular canal defect. Complete obstruction of the small pulmonary arterial lumen resulting from acute fibrous proliferation and atrophy of the peripheral arterial media, which were considered absolute operative contraindications, were characteristic in six patients with Down's syndrome. Morphometric analysis of medial thickness revealed that thinning of the media of the small pulmonary arteries is generally observed at around 6 months of age in patients with complete atrioventricular canal defect and that the media in patients who have complete atrioventricular canal defect and Down's syndrome was thinner than that in such patients without Down's syndrome. These results suggest that thinning of the media as a result of two factors--Down's syndrome and aging--facilitates the rapid occurrence of fibrous intimal proliferation. Therefore intracardiac repair is desirable within 6 months of life, before medial thinning, in patients with complete atrioventricular canal defect and Down's syndrome. Excluding patients with absolute operative contraindications, the scores of the index of pulmonary vascular disease in operative survivors were below 2.0 and death occurred when scores were more than 2.2. The pulmonary vascular resistances measured in room air and by the oxygen inhalation and tolazoline tests in patients with operative contraindications were more than 7.3, 3.8, and 6.6 units.m2, respectively. We thus conclude that lung biopsy should be undertaken for patients in whom pulmonary vascular resistance is beyond these values to determine the appropriateness of surgical intervention.
Institutional address: Department of Thoracic and Cardiovascular Surgery Tohoku University School of Medicine Sendai Japan.
(REFERENCE 100 OF 102) 93341176
Chapelier A Vouhe P Macchiarini P Lenot B Cerrina J Le Roy Ladurie F Parquin F Herve P Brenot F Lafont D et al Comparative outcome of heart-lung and lung transplantation for pulmonary hypertension.
In: J Thorac Cardiovasc Surg (1993 Aug) 106(2):299-307
ISSN: 0022-5223
Despite the development of several lung transplantation procedures, the most advantageous for pulmonary hypertension remains controversial. Between 1986 and February 1992, 30 patients with end- stage primary pulmonary hypertension (n = 24), chronic pulmonary embolism (n = 4), and hystiocytosis X (n = 2) underwent heart-lung (n = 21), double lung (n = 8), or single lung (n = 1) transplantation. Indications for double lung transplantation were similar to those for heart-lung transplantation, and the preoperative clinical and hemodynamic parameters were not significantly different between the two groups. There were no intraoperative deaths, but two reoperations were needed for pleural hematoma. Five early deaths were related to graft failure (two heart-lung transplantations), mediastinitis (one heart-lung transplantation), multiorgan failure (one double lung transplantation), and aspergillosis (one double lung transplantation). There was a similar improvement in early (days 0 and 2) and late (6 months postoperatively) right-sided hemodynamic function in patients undergoing heart-lung and double lung transplantation. Three double lung transplant recipients had early and reversible left ventricular-failure. The early postoperative course of the one patient who had single lung transplantation was characterized by severe pulmonary edema, left ventricular failure, and persistent desaturation and later on by moderate pulmonary hypertension and an important ventilation/perfusion mismatch. The pulmonary function results were also similar in the heart-lung and double lung transplantation groups. The overall projected 2- and 4- year survivals were 49% and 41%, respectively, and were not significantly different between the heart-lung and double lung recipients. Results demonstrate that heart-lung and double lung transplantation are equally effective in obtaining early and durable right-sided hemodynamic and respiratory improvement and similar respiratory function. In patients with pulmonary hypertension, double lung transplantation should be preferred to single lung transplantation because of the critical postoperative course and the uncertain long-term results of single lung transplantation.
Institutional address: Department of Thoracic and Vascular Surgery Hopital Marie-Lannelongue Plessis Robinson France.
*****LANCET*****
(REFERENCE 101 OF 102) 99258396
Elstein D Klutstein MW Lahad A Abrahamov A Hadas-Halpern I Zimran A Echocardiographic assessment of pulmonary hypertension in Gaucher's disease.
In: Lancet (1998 May 23) 351(9115):1544-6
ISSN: 0140-6736
BACKGROUND: Enzyme therapy has been shown to decrease the signs and symptoms of Gaucher's disease. A few patients, however, develop pulmonary hypertension on such treatment. We investigated the frequency of pulmonary hypertension in Gaucher's disease. METHODS: We studied 134 adults with type 1 Gaucher's disease, including 73 patients on enzyme replacement, with echocardiography. We measured tricuspid incompetence (TI) with continuous-wave doppler. Pulmonary hypertension was indicated by a TI gradient of more than 30 mm Hg. FINDINGS: Nine (7%) patients had pulmonary hypertension: all were treated and six had undergone splenectomy. Chest radiographs confirmed the presence of pulmonary hypertension in these patients as well as in most patients with TI gradients of 25-29 mm Hg. INTERPRETATION: The confounding effects of disease severity and splenectomy in many treated patients precluded definitive conclusion of cause and effect. Nonetheless, we found an unexpectedly high rate of pulmonary hypertension and recommended routine echocardiographic monitoring of all treated and untreated patients with type 1 Gaucher's disease. We also suggest consideration of treatment withdrawal if the TI gradient progresses to more than 30 mm Hg.
Registry Numbers: EC 3.2.1.- (alglucerase) EC 3.2.1.- (imiglucerase) EC 3.2.1.45 (Glucosylceramidase)
Institutional address: Gaucher Clinic Jerusalem Israel.
(REFERENCE 102 OF 102) 98397221
Gaine SP Rubin LJ Primary pulmonary hypertension.
In: Lancet (1998 Aug 29) 352(9129):719-25
ISSN: 0140-6736
Primary pulmonary hypertension (PPH) is a progressive disease characterised by raised pulmonary vascular resistance, which results in diminished right-heart function due to increased right ventricular afterload. PPH occurs most commonly in young and middle-aged women; mean survival from onset of symptoms is 2-3 years. The aetiology of PPH is unknown, although familial disease accounts for roughly 10% of cases, which suggests a genetic predisposition. Current theories on pathogenesis focus on abnormalities in interaction between endothelial and smooth-muscle cells. Endothelia-cell injury may result in an imbalance in endothelium-derived mediators, favouring vasoconstriction. Defects in ion-channel activity in smooth-muscle cells in the pulmonary artery may contribute to vasoconstriction and vascular proliferation. Diagnostic testing primarily excludes secondary causes. Catheterisation is necessary to assess haemodynamics and to evaluate vasoreactivity during acute drug challenge. Decrease in pulmonary vascular resistance in response to acute vasodilator challenge occurs in about 30% of patients, and predicts a good response to chronic therapy with oral calcium-channel blockers. For patients unresponsive during acute testing, continuous intravenous epoprostenol (prostacyclin, PGI2) improves haemodynamics and exercise tolerance, and prolongs survival in severe PPH (NYHA functional class III-IV). Thoracic transplantation is reserved for patients who fail medical therapy. We review the progress made in diagnosis and treatment of PPH over the past 20 years.
Institutional address: Division of Pulmonary and Critical Care Medicine University of Maryland School of Medicine Baltimore 21201 USA.