*****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 vasod