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Biomedical subjects

L C Pelletier

Publications and source records attributed to L C Pelletier.

At least 37 records · Page 2Linked to original sources

Nitric oxide inhalation in the treatment of primary graft failure following heart transplantation.

BACKGROUND: Primary graft failure from right or left ventricular insufficiency remains a serious cause of early death following heart transplantation. Inhaled nitric oxide (NO) is a potent pulmonary vasodilator that could decrease pulmonary pressure and improve right ventricular function. METHODS: Two cases of early graft failure following orthotopic heart transplantation were treated with NO inhalation. The treatment consisted of inhalation of 20 ppm of NO, introduced 4 to 6 hours following transplantation, in 2 patients supported with high doses of inotropic agents and vasopressors in addition to the intra-aortic balloon pump. RESULTS: In the first and second cases, NO inhalation resulted in a decrease in pulmonary artery pressure, in a decrease in pulmonary vascular resistance and in an increase in cardiac index. In the second patient, systemic oxygenation improved markedly 30 minutes after initiation of NO. In the 2 patients, NO inhalation, mechanical ventilation and the intra-aortic balloon pump were weaned 4 days following transplantation. CONCLUSION: Primary graft failure from donor ischemic damage, reperfusion injury or pulmonary hypertension remains a serious complication. The use of an intra-aortic balloon pump, inotropic agents and of inhaled NO appears to offer the best support for recovery of donor heart function. Primary graft failure from right or left ventricular insufficiency remains a serious cause of early mortality following heart transplantation. Ischemic damage of donor heart, reperfusion injury or pulmonary hypertension are the main causes of early graft failure. Although the cause is multifactorial, treatment of primary organ failure remains difficult with dismal results. The objective of the present study was to review the result of 2 patients with donor right heart failure following heart transplantation treated with inhaled nitric oxide (NO).

Administration, Inhalation↗

A 10-year experience with intravenous thymoglobuline in induction of immunosuppression following heart transplantation.

BACKGROUND: Intravenous thymoglobuline (125 mg a day for 3 days, Institut Mérieux, France) has been used to induce immunosuppression following heart transplantation. Cyclosporine and prednisone, with and without azathioprine or mycophenolate mofetil were used as maintenance immunosuppression. OBJECTIVE: The objective of the study was to determine the clinical effect of antibody induction of immunosuppression following heart transplantation. METHODS: A retrospective analysis of the clinical experience at the Montreal Heart Institute. From 1988 to 1998, 163 patients were administered a 3-day course of intravenous thymoglobuline immediately following heart transplantation (Group 1). From 1983 to 1987 and during an isolated period in 1994, intravenous and oral cyclosporine was used immediately following heart transplantation in 48 patients (Group 2). Routine endomyocardial biopsies were performed in all patients and only moderate and severe rejection was treated. RESULTS: One, 5- and 10-year actuarial survival rate averaged 85%+/-3, 77%+/-4 and 67%+/-5 in Group 1 compared with 88%+/-5, 81%+/-6 and 76%+/-6 in Group 2 (p = 0.5). At 1 year, the freedom rate from an episode of acute rejection averaged 43%+/-4 in Group 1 and 30%+/-7 in Group 2 (p = 0.03) and the freedom rate from an episode of infection averaged 44%+/-4 in Group 1 and 31%+/-7 in Group 2 (p = 0.2). At 1, 5 and 10 years, the freedom rate from graft coronary artery disease averaged 93%+/-2, 68%+/-5 and 50%+/-7 in Group 1 compared with 93%+/-4, 58%+/-8 and 30%+/-8 in Group 2 (p = 0.1) and the freedom rate from cancer averaged 98%+/-1, 91%+/-3 and 67%+/-8 in Group 1 compared with 100%, 95%+/-3 and 77%+/-8 in Group 2 (p = 0.2). There was no side-effect related to the systemic injection of thymoglobuline. CONCLUSION: In a cyclosporine based protocol of immunosuppression, induction with an initial 3-day course of intravenous thymoglobuline is associated with a lower rate of acute rejection. Moreover, the risk of infection and of developing cancer is not increased whereas there was a trend towards a lower incidence of coronary atherosclerosis 5 and 10 years after transplantation.

Adult↗

Beating heart coronary artery bypass grafting: technical aspects and results in 200 patients.

OBJECTIVE: To describe the initial experience of the first 200 patients who underwent coronary artery bypass grafting (CABG) on beating hearts at the Montreal Heart Institute, Montreal. DESIGN: A prospective cohort of 200 patients was analyzed to study immediate and short term (two-year follow-up) results. SETTING: Patients underwent CABG at the Montreal Heart Institute from February 1996 to June 1998. The first 30 patients underwent CABG without the use of a myocardial wall stabilizer (group 1), and a myocardial wall stabilizer was used in the following 170 patients (group 2). PATIENTS: Group 1 patients averaged 60+/-10 years of age compared with 66+/-10 years in group 2 (P=0.002). Twelve patients (40%) in group 1 had unstable angina compared with 107 patients (63%) in group 2 (P=0.03). INTERVENTIONS: Group 1 patients underwent 1.7+/-0.7 CABG per patient compared with 2.4+/-0.8 grafts per patient in group 2 (P=0.001). Sixty-seven patients (39%) in group 2 had an obtuse marginal coronary artery grafted, and 145 patients (73%) of both groups had a complete myocardial revascularization. RESULTS: Ten patients (5%) in both groups were converted to cardiopulmonary bypass during surgery. Seven patients (3.5%) died postoperatively: five from myocardial infarction, one from aortic dissection and rupture, and one from arrhythmia. Seventeen patients (8.5%) suffered a perioperative myocardial infarction. In groups 1 and 2, respectively, actuarial survival was 100% and 95+/-2%, and freedom rate from reoperation, percutaneous balloon dilation and recurrent myocardial infarction averaged 93+/-4% and 97+/-2% 18 months following CABG. CONCLUSION: CABG on beating hearts appears to be an alternative approach to the use of cardiopulmonary bypass in selected patients.

Aged↗

Videoassisted thrombectomy of mechanical prosthetic heart valves.

BACKGROUND AND AIM OF THE STUDY: Thrombosis of a bileaflet mechanical heart valve is a life-threatening clinical event. Surgical thrombectomy of bileaflet mechanical prostheses remains an appropriate treatment in selected patients. METHODS: Between 1996 and 1998, five patients (three men, two women; average age 56 +/- 1 years; range: 56 to 66 years) with thrombosis of left-sided bileaflet mechanical valves were treated with videoassisted thrombectomy of the prosthesis. Four patients had thrombosis of a bileaflet mitral mechanical valve, and one patient had thrombosis of an aortic valve prosthesis. Preoperatively, patients were in either NYHA functional class IV (n = 4) or class I (n = 1). Surgery was performed through a right anterior thoracotomy or a median sternotomy. A rigid 30 degrees thoracoscope was inserted into the left atrium or aorta to visualize the thrombosed valve. The thrombus was extracted and the prosthesis under-surface examined and cleaned. Leaflet mobility, assessed with transesophageal echocardiography, was normal following surgical thrombectomy. RESULTS: Mean cardiopulmonary bypass time was 102 +/- 30 min; mean aortic cross-clamping time was 47 +/- 25 min. There was no hospital mortality; mean hospital stay was 9 +/- 1 days (range: 6 to 11 days). Anticoagulation with intravenous heparin was resumed 24 h after surgery. Three patients were discharged on coumarin treatment alone; two patients received aspirin plus coumarin. Mean postoperative follow up was 7 +/- 8 months (range: 1 to 21 months). One patient died 21 months after thrombectomy of a mitral prosthesis, with an unconfirmed diagnosis of recurrent mitral valve dysfunction. At 1-15 months after surgery, four patients are in NYHA class I, without evidence of prosthesis dysfunction. CONCLUSION: Videoassisted thrombectomy of a bileaflet mechanical heart valve is a treatment option in patients with acute thrombosis of the prosthesis.

Anticoagulants↗

Conversion of cyclosporine A to tacrolimus following heart transplantation.

BACKGROUND: Cyclosporine A (CyA) is ususally the immunosuppressive drug of choice in organ transplantation; however, some side effects have limited its use. Tacrolimus is a novel immunosuppressive drug that is more potent than CyA, and has been used as a rescue agent following heart transplantation when the use of CyA is undesirable or inefficient. PATIENTS AND METHODS: Since 1996, 14 heart transplant recipients under CyA were switched to tacrolimus therapy, for refractory rejection or intolerance, to conventional immunosuppression. RESULTS: After a mean of 35+/-7 months of treatment, tacrolimus was substituted for CyA therapy. The reason for substitution was refractory rejection in six patients, gingival hypertrophy in five patients, hypertrichosis in one patient, severe arterial hypertension in one patient and hepatotoxicity in one patient. Five patients underwent a successful rescue therapy and one patient died of refractory rejection despite the use of tacrolimus. All patients with CyA side effects recovered with tacrolimus. After conversion from CyA to tacrolimus, the number of episodes of acute rejection decreased from a mean of 0.42+/-0.17 to 0.14+/-0.09 episodes/patient/month under CyA and tacrolimus therapy (P=0.11), respectively. The mean dose of prednisone was 0.18+/-0.06 mg/kg/day before compared with 0.06+/-0.01 mg/kg/day after conversion from CyA to tacrolimus (P=0.09). Creatinine serum levels averaged 124+/-7 mmol/L under CyA treatment compared with 113+/-7 mmol/L with tacrolimus therapy (P=0.002). CONCLUSION: In patients with refractory rejections or intolerance to CyA after heart transplantation, conversion to tacrolimus-based immunosuppression is safe and effective.

Adult↗

[Results of surgery after failed mitral percutaneous dilatation].

OBJECTIVES: Percutaneous balloon mitral valve commissurotomy (BMC) is an alternative to surgical commissurotomy. Complications following BMC includes mitral regurgitation, iatrogenic atrial septal defect, residual mitral stenosis, and pericardial hemorrhage. This study analyzes the outcomes of surgery following failed BMC for mitral stenosis. METHODS: In a series of 298 patients treated with BMC, 53 patients (17.7%) had a complication that necessitated a surgical treatment. Twenty-eight patients needed an immediate surgery before the discharge (group I) and 25 patients were operated on an elective basis (group II). RESULTS: In group I, 27 patients have been operated and one died before the operation. In 21 patients an acute mitral regurgitation occurred, 3 patients had a residual mitral stenosis, and 3 had a left atrial perforation. The operation consisted of 26 mitral valve replacements, 20 concomitant reparations of iatrogenic atrial septal defect, and one open mitral valve commissurotomy. Operative mortality was 3.7% (1 out of 27). In group II, 25 patients have been operated at a mean 18 +/- 14 months after BMC. In the 25 patients the operation was indicated for significant mitral regurgitation (2 + and more). The operation consisted of 25 mitral valve replacements, 9 concomitant reparations of iatrogenic atrial septal defect, 3 patients had also coronary artery bypasses. The operative mortality was 8% (2 out of 25). The echocardiographic score was similar for both groups, it was 8.4 +/- 2.0 in group I and 8.0 +/- 1.5 in group II (P = NS). Despite these complications following failed BMC, surgery appears a safe procedure with an acceptable mortality.

Aged↗

Effect of Celsior and University of Wisconsin solutions on myocardial metabolism and function after warm ischemia.

BACKGROUND: Optimal preservation of donor hearts remains a significant concern during transplantation. Organ shortage led to an increase in the use of damaged hearts. METHODS: To study the effect of preservation solutions on recovery of myocardial metabolism and function after warm ischemia, 10 dogs underwent 30 minutes of warm global ischemia under cardiopulmonary bypass. The animals were then administered 1 liter of Celsior (5 dogs), an extracellular crystalloid solution or 1 liter of University of Wisconsin solution (5 dogs), cooled at 4 degrees C, followed by 60 minutes of cold preservation and 30 minutes of warm blood reperfusion. Interstitial myocardial pH and pO2 changes were measured. The left ventricle dP/dt was measured before and after the ischemic episode, as where creatine kinase, troponine T and lactate serum levels. RESULTS: Tissue pH averaged 6.9+/-0.1, 6.2+/-0.1, 6.7+/-0.1 and 6.8+/-0.1 before and after warm ischemia, following the 60 minutes of cold preservation and the reperfusion period in animals treated with the Celsior solution, compared to 6.8+/-0.1, 6.4+/-0.1, 7+/-0.1 and 6.8+/-0.2 respectively in dogs treated with the University of Wisconsin solution (p<0.05). Oxygen tension in the myocardium averaged 36+/-8 mmHg before warm ischemia and 59+/-31 mmHg after in animals that received Celsior compared to 30+/-10 mmHg and 49+/-7 mmHg in dogs treated with University of Wisconsin (p>0.05). Global myocardial function decreased significantly following reperfusion compared to baseline in both groups of animals. The serum levels of creatine kinase, troponine T and lactate increased significantly during the experiment although there was no significant difference between the 2 groups. CONCLUSION: Both preservation solutions (Celsior and University of Wisconsin) resulted in suboptimal recovery of myocardial function and metabolism when administered after a period of warm ischemia. Strategies to improve recovery of damaged donor hearts remain to be appropriately defined.

Acid-Base Equilibrium↗

Can L-arginine improve myocardial protection during cardioplegic arrest? Results of a phase I pilot study.

BACKGROUND: L-arginine appears to improve myocardial protection during cardioplegic arrest in animal models. METHODS: To study the clinical effect and safety of L-arginine in humans, a phase I pilot study was performed with 50 patients who underwent coronary artery bypass grafting. We randomly assigned half to a treatment group, which received 1 g of L-arginine administered during the first 30 minutes of cardioplegic arrest induced by either warm or cold blood cardioplegia, and half to a control group, which did not receive L-arginine supplementation. RESULTS: Age, sex, and preoperative clinical status were similar in both groups. Seventeen patients of each group were administered intermittent warm antegrade blood cardioplegia, whereas the solution needed to be cooled to obtain complete standstill of the remaining eight hearts in each group. An internal thoracic artery graft to the left anterior descending coronary artery was performed in all patients. There was no death and no myocardial infarction in the treatment group, but there were one death and two infarctions in the control group. The amount of serial release of troponin I during the first 72 hours after the operation was similar between the L-arginine group and the control group (p > 0.05). Peak serum troponin levels averaged 4.9 +/- 1.0 microg/L in the arginine group and 3.9 +/- 1.0 microg/L in the control group (p > 0.05). A multivariate analysis of variance showed no effect of L-arginine (p > 0.05) but a significant effect of the temperature of the cardioplegic solution on the release of troponin I (p < 0.05). Serum troponin I levels averaged 2.2 +/- 0.4 microg/L, 4.5 +/- 0.4 microg/L, and 6.9 +/- 0.4 microg/L in the patients with cold cardioplegia and 1.4 +/- 0.3 microg/L, 2.4 +/- 0.3 microg/L, and 3.3 +/- 0.3 microg/L in the patients with warm cardioplegia 1, 2, and 6 hours, respectively, postoperatively. CONCLUSIONS: The administration of 1 g of L-arginine during the first 30 minutes of blood cardioplegic arrest did not result in a decrease in the postoperative release of cardiac enzyme; however, cold cardioplegic arrest significantly increased the release of cardiac troponin I postoperatively. There was no significant side effect related to the addition of L-arginine to the cardioplegic solution.

Arginine↗

15-year experience with the Carpentier-Edwards pericardial bioprosthesis.

BACKGROUND: The aim of the study was to evaluate the late results of the Carpentier-Edwards pericardial bioprosthesis, which we have been implanting since 1981. METHODS: The 812 patients who underwent heart valve replacement with a Carpentier-Edwards pericardial bioprosthesis between 1981 and 1996 were reviewed. Their clinical, operative, and follow-up data were prospectively recorded in a computerized database. All but 29 patients were available for follow-up (96% completeness), which averaged 58 months and totaled 3,000 patient-years. RESULTS: There were 598 aortic valve replacements (74%), 149 mitral valve replacements (18%), and 65 double valve replacements (8%). The mean age at the time of surgery was 65 years (range, 18 to 88 years), with 24% of the patients under the age of 60 years. Preoperatively, 558 patients (69%) were in New York Heart Association functional class III or IV. Associated surgical procedures included coronary artery bypass grafting in 219 patients (27%) and tricuspid or mitral valve repair in 40 (5%). Previous cardiac operations had been performed in 149 patients, including 134 valve-related procedures. There were 49 early deaths overall (6%): 29 after aortic valve replacement (4.8%), 11 after mitral valve replacement (7.4%), and 9 with double valve replacement (13.8%). There were 120 late deaths for a 10-year actuarial survival rates of 69%+/-3%, 58%+/-7%, and 38%+/-10% for aortic, mitral, and double valve replacement, respectively. The 14-year survival rate for aortic valve replacement patients is 68%+/-3%. The 10-year and 14-year actuarial freedom rates from events after aortic valve replacement are 92% +/-2% and 88%+/-4% for thromboembolism, 96%+/-1% and 92%+/-4 for endocarditis, 91%+/-2 and 72%+/-6% for reoperation, and 93%+/-2% and 80%+/-5% for structural dysfunction of the valve. The 10-year actuarial freedom rates from events after mitral and double valve replacement are 93%+/-3% and 89%+/-4% for thromboembolism, 95%+/-3% and 88%+/-5% for endocarditis, 76%+/-7% and 70%+/-14% for reoperation, and 81%+/-7% and 72%+/-15% for structural dysfunction. No primary tissue failure of the prosthesis in any position was observed in the 357 patients aged 70 years or more at the time of valve implantation. CONCLUSIONS: The Carpentier-Edwards pericardial valve offers excellent clinical results and durability, particularly in the aortic position and for patients older than 70 years of age.

Actuarial Analysis↗

Mitroflow pericardial bioprosthesis experience in aortic valve replacement > or =60 years of age.

BACKGROUND: The Mitroflow pericardial bioprosthesis (model 11), a second-generation pericardial prosthesis, has clinical performance assessment to 10 years. The authors previously recommended the prosthesis for aortic valve replacement in patients 70 years or older. The purpose of the current assessment is to report on performance in patients 60 years or older undergoing aortic valve replacement. METHODS: This bioprosthesis was implanted in 161 patients (mean age, 69.5+/-6.3 years; range, 60 to 94 years) with aortic valve replacement from 1982 to 1992. There were 84 patients 60 to 69 years (mean, 64.5+/-3.1 years) and 77 patients 70 years or older (mean, 74.8+/-4.3 years). Of the total population, concomitant procedures were performed in 63 patients (39.1%); of these, coronary artery bypass grafting was performed in 39 (24.2%). RESULTS: The early mortality was 4.8% (4 patients) for the 60 to 69-year age group and 10.4% (8) for those 70 years or older (not significant). The late mortality was 4.4%/patient-year (27) for those 60 to 69 years and 6.9%/ patient-year (35) for those 70 years or older (not significant). The patient survival for those 60 to 69 years was 58.0%+/-6.3% and for those 70 years or older, 45.3%+/-5.9% at 10 years (p < 0.05). The valve-related mortality for those 60 to 69 years was 0.82%/patient-year (5) and for those 70 years or older, 1.58%/patient-year (8) (not significant). The reoperation rate for those 60 to 69 years was 3.29%/patient-year (20) and for those 70 years or older, 1.0%/patient-year (5) (p < 0.05). The structural valve deterioration rate for those 60 to 69 years was 3.13%/ patient-year (19) and for those 70 years or older, 1.2%/ patient-year (6) (p < 0.05). CONCLUSIONS: The Mitroflow pericardial bioprosthesis remains recommended for aortic valve replacement in patients 70 years and older.

Age Factors↗

In elective coronary artery bypass grafting, preoperative troponin T level predicts the risk of myocardial infarction.

OBJECTIVE: Several combinations of risk factors for death or cardiac events after coronary artery bypass grafting have been described. We studied the prognostic value of the preoperative serum levels of cardiac troponin T. METHODS: We studied 468 patients who underwent elective coronary artery bypass grafting. Preoperative and postoperative levels of cardiac troponin T and creatine kinase MB, electrocardiograms, clinical data, and events were recorded prospectively. No acute ischemic changes were present on the electrocardiogram before the operations, and preoperative creatine kinase MB serum levels were within normal limits in all patients. RESULTS: Ninety-seven (97/468, 21%) patients had serum levels of troponin T greater than 0.02 microg/L within 24 hours before coronary artery bypass grafting. Hospital mortality was similar in this group and in the patients with preoperative levels less than 0.02 microg/L (1% in each group). Nine patients (9/97, 9%) with elevated levels of troponin T before the operation had a perioperative myocardial infarction compared with 12 patients (12/371, 3%) among the group with lower troponin T levels (p = 0.015, RR = 2.9). Congestive heart failure occurred in 10 (10/97, 10%) and 8 (8/371,2%) patients, respectively (p = 0.0009, RR = 4.8). Intensive care unit (p = 0.002) and postoperative hospital length of stay (p = 0.09) were all longer in patients with the elevated preoperative troponin T level. In a logistic regression analysis, troponin T level before the operation was the variable most strongly correlated with postoperative myocardial infarction (p = 0.003). CONCLUSION: Preoperative troponin T stratification before coronary artery bypass grafting identifies a subgroup of patients with increased risk of postoperative cardiac complications.

Biomarkers↗

Metabolic monitoring during continuous warm- and cold-blood cardioplegia by means of myocardial tissue pH and PO2.

OBJECTIVES: To study the changes in myocardial tissue pH and PO2 during cold- and warm-blood cardioplegic arrests. DESIGN: An experimental study in dogs. METHODS: Nine dogs underwent the following procedures: 30 minutes with an empty heart beating under cardiopulmonary bypass (control period); 30 minutes of warm (33 degrees C) cardioplegic arrest with a 1:4 mix of crystalloid in blood solution administered continuously at 150 mL/min; 30 minutes of cold (15 degrees C) cardioplegic arrest; and 30 minutes of myocardial reperfusion. The cardioplegic blood solution was administered antegradely through the ascending aorta. MAIN OUTCOME MEASURES: Tissue pH and PO2. Arterial and coronary sinus oxygen content and myocardial consumption calculated. RESULTS: There was a modest but significant increase in the left anterior descending (LAD) and circumflex (Cx) tissue pH throughout the experiment. PmO2 in the LAD territory averaged 44 (7) mm Hg (mean and standard error of the mean) during the bypass period, 123 (23) mm Hg at the termination of warm cardioplegic arrest, 146 (28) mm Hg at the end of cold arrest and 66 (17) mm Hg after reperfusion. Oxygen consumption averaged 0.65 (0.15) mL/min during the bypass period, 0.3 (0.18) mL/min at the end of warm arrest, 0.25 (0.16) mL/min at the end of cold arrest and 0.45 (0.08) mL/min after reperfusion (p < 0.05). Oxygen delivery to the LAD territory was greater than myocardial oxygen consumption by an average of 2.02 (0.4) mL/min during bypass, 2.02 (0.62) mL/min after warm arrest, 2.12 (0.5) mL/min after cold arrest and 1.55 (0.25) mL/min after reperfusion (p > 0.05). CONCLUSIONS: During cardioplegic arrest, tissue PO2 increased and oxygen consumption decreased significantly, whereas tissue pH remained normal, suggesting that continuous warm- and cold-blood cardioplegia maintained aerobic glycolysis during myocardial arrest. Thus, the increase in myocardial tissue PmO2 during cardioplegic arrest reflects the decrease in myocardial oxygen consumption while maintaining oxygen supply.

Animals↗

L-arginine prevents cyclosporin A-induced pulmonary vascular dysfunction.

BACKGROUND: Cyclosporin A is known to alter endothelium-dependent responses to different agonists. Few data are available concerning the effect of cyclosporin A on the pulmonary vascular bed. METHODS: The endothelium-dependent responses to acetylcholine (20 micrograms), bradykinin (5 micrograms), and substance P (5 micrograms) were investigated in a dog model of left lung autoperfusion at constant flow. RESULTS: The vasodilator response to bradykinin and substance P was significantly decreased with cyclosporin A (20 mg) administration. The average decreases in pulmonary arterial pressure with bradykinin were 5.4 +/- 1.5 mm Hg and 2.4 +/- 0.4 mm Hg before and after cyclosporin A administration, respectively (p = 0.04). The average decreases in pulmonary arterial pressure with substance P were 4.4 +/- 1.0 mm Hg and 1.8 +/- 0.5 mm Hg before and after cyclosporin A administration, respectively (p = 0.04). The responses to acetylcholine and the endothelium-independent relaxing agent nitroglycerin were not significantly affected by cyclosporin A. The effects of cyclosporin A on endothelium-dependent responses to bradykinin and substance P were overcome by the administration of L-arginine (200 mg/kg intravenously). The decreased response to bradykinin and substance P after cyclosporin A administration was not significantly affected by indomethacin, a cyclooxygenase inhibitor. The pulmonary angiotensin-converting enzyme activity was also measured using [3H]benzoyl-phenylalanyl-glycyl-proline, an inactive angiotensin-converting enzyme substrate. There was an average [3H]benzoyl-phenylalanyl-glycyl-proline hydrolysis of 54% +/- 2% and 55% +/- 2% before and after cyclosporin A administration, respectively (not significant). CONCLUSIONS: The present study suggests that cyclosporin A selectively decreases endothelium-dependent responses to bradykinin and substance P without affecting the cyclic guanosine monophosphate-dependent pathway in the canine pulmonary vascular bed. The decreased endothelium-dependent responses to bradykinin and substance P are not related to increased angiotensin-converting enzyme activity. The toxic effect of cyclosporin A on endothelium-dependent responses is reversible by the administration of L-arginine, a source of substrate for nitric oxide.

Acetylcholine↗

Does retrograde administration of blood cardioplegia improve myocardial protection during first operation for coronary artery bypass grafting?

BACKGROUND: The objective of this study was to evaluate the value of retrograde blood cardioplegia in coronary artery bypass grafting. METHODS: In 1994 and 1995, 224 patients undergoing first-time isolated coronary artery bypass grafting were randomized to antegrade (112 patients, group 1) or retrograde (112 patients, group 2) administration of blood cardioplegia. In group 1, 76 patients were given warm cardioplegia (at 33 degrees C) and 36 had cold cardioplegia (< 20 degrees C), whereas in group 2 cardioplegia was warm in 77 patients and cold in 35. The two randomization groups had similar demographic and angiographic characteristics. The number of grafted coronary arteries averaged 2.9 +/- 0.7 in group 1 and 2.8 +/- 0.7 in group 2. Total duration of cardiopulmonary bypass (78 +/- 23 and 75 +/- 21 minutes) and of aortic cross-clamping (47 +/- 16 and 46 +/- 16 minutes), total volume of infusion of the crystalloid component of cardioplegia (988 +/- 297 and 1016 +/- 595 mL), and total duration of infusion of cardioplegia (23 +/- 10 and 22 +/- 11 minutes) were similar (p > 0.05). RESULTS: There was no death in group 1 and one in group 2 as a result of a pulmonary embolus, for a global early mortality of 0.45%. The numbers of perioperative myocardial infarction (5 versus 3), congestive heart failure (4 versus 5), postoperative hemorrhage (4 versus 4), and stroke (1 versus 2) were also similar (p > 0.05). Release curves of total creatine kinase, creatine kinase-MB by serum activity and mass concentration, and troponin T were not significantly different (p > 0.05) between the two groups. For the 216 patients without perioperative myocardial infarction, peak enzyme release of creatine kinase-MB at 24 hours averaged 23 +/- 22 and 20 +/- 18 IU/L, and that of troponin T averaged 1.1 +/- 1.1 and 1.3 +/- 1.5 micrograms/L at 6 hours for the antegrade and the retrograde groups, respectively (p > 0.05). CONCLUSIONS: Our results indicate no evidence that the retrograde method of cardioplegic infusion improves myocardial protection during first operation for isolated coronary revascularization compared with the usual antegrade route.

Adult↗

[Cardiac surgery in Quebec: Do we have too many centers? Too many surgeons? Too many patients?].

OBJECTIVE: In restructuring the Quebec health care system with hospital budget cuts, salary ceiling of physicians and a small number of practising cardiac surgeons, the future of this specialty needs to be defined beyond individual self-interest. To evaluate the actual situation and to suggest changes that will improve surgical care delivery in cardiac surgery, surgeon and centre case loads in the province of Quebec were reviewed. DESIGN: Retrospective study. SETTING: Province of Quebec, 1994. PATIENTS: Patients who underwent coronary artery bypass grafting in 1994. RESULTS: The rate of coronary bypass grafting in Quebec was similar to that in Canada as a whole. The number of patients undergoing coronary artery bypass grafting increased at a rate of 6.5%/year during the five years preceding 1994, when operations numbered 5000. Thus, 7000 procedures will be performed in the year 2000 if the actual increase remains similar. There are 12 centres performing cardiac surgery in Quebec, with one centre/600,000 population and 3.4 surgeons/centre, compared with one centre/800,000 population and 3.7 surgeons/centre in Canada. In the year 2000, to accommodate 7000 cases, 18 centres will be required for a minimal case load per centre (300 cases/centre) or nine centres for an optimal case load per centre (700 cases). CONCLUSION: Each centre of cardiac surgery should perform an optimal volume of cases to achieve maximal use of human and physical resources devoted to the care of cardiac surgical patients in the province of Quebec.

Cardiac Care Facilities↗

Myocardial distribution of cardioplegia administered by antegrade and retrograde routes to ischemic myocardium.

OBJECTIVE: To study the distribution of a cardioplegic solution delivered by antegrade and retrograde routes to ischemic myocardium. Retrograde administration has been suggested to improve protection of the ischemic myocardium. However, there are insufficient data on perfusion of ischemic and necrotic zones by the retrograde route. DESIGN: A laboratory study in dogs. METHOD: In 12 dogs, 500 mL of hyperkalemic crystalloid cardioplegia containing 0.5 mCi of thallium-201 was injected antegradely or retrogradely through the coronary sinus after 3 hours of occlusion and 2 hours of reperfusion of the left anterior descending coronary artery. Myocardial distribution of the cardioplegic solution was measured by computer planimetry in the normally perfused zone, in the ischemic area and in the necrotic zone. RESULTS: The mean (and standard deviation) area at risk of ischemia (% of the left ventricle) delimited by Evans blue perfusion was smaller in dogs receiving a retrograde injection than in those receiving an antegrade injection (34% [3%] v. 42% [4%], p = 0.15). The infarct size (% of the area at risk indicated by triphenyltetrazolium dye) averaged 25% (11%) and 20% (7%) respectively (p = 0.36). The ratio of thallium-201 activity in ischemic to normal myocardium averaged 76% (13%) in the retrograde and 89 (12%) in the antegrade groups (p = 0.75). The ratio of thallium activity of infarct to normal myocardium averaged 56% (8%) in the retrograde group and 93% (19%) in the antegrade group (p = 0.18). Large areas of hypoactivity in the left ventricular myocardium were noted on scintigraphic imaging in all dogs that received retrograde perfusion. CONCLUSIONS: The retrograde injection of cardioplegia through the coronary sinus does not improve the distribution of cardioplegic solution in the acutely ischemic myocardial area nor in the zone of acute infarction in the dog. Because some cells may remain viable in the border zone and into the necrotic area, retrograde cardioplegia may result in suboptimal protection and incomplete prevention of further damage to the myocardium.

Animals↗

Comparison of Neoral and Sandimmune cyclosporine for induction of immunosuppression after heart transplantation.

OBJECTIVE: To compare the efficacies of Neoral cyclosporine (N-CSA [Sandoz]) and Sandimmune cyclosporine (S-CSA [Sandoz]) in induction of immunosuppression immediately after heart transplantation. DESIGN: A prospective and a retrospective cohort. SETTING: Patients who underwent heart transplant operations at the Montreal Heart Institute, Montreal, Quebec. PATIENTS: To evaluate the results of both formulations of cyclosporine (CSA), a cohort of 20 consecutive patients who underwent heart transplant operations between 1994 and 1995, and who were administered N-CSA, azathioprine, prednisone and intravenous CSA (10 patients) or rabbit antithymocyte globulin (RATG) (10 patients) were compared with 21 patients who underwent heart transplant operations between 1993 and 1994, and were treated with RATG, S-CSA, azathioprine and prednisone. Preoperative patient characteristics were similar in all groups. RESULTS: There were no significant differences in daily CSA doses after the fourth day following transplantation. Higher trough levels of CSA were observed during the first four days, from days 12 to 14 and one month after transplantation in the two groups that were administered N-CSA. Serum levels of creatinine were significantly higher three to five days after transplantation in both groups who received N-CSA. Creatinine levels were also higher between days 13 and 14 in patients who received N-CSA and intravenous CSA. Oral administration of N-CSA was stopped temporarily in two patients (20%) who received intravenous CSA because of a sudden decrease in urine output and rise in serum creatinine. Three months after transplantation actuarial freedom rate from acute rejection averaged 33 +/- 10% in the S-CSA group, 10 +/- 9% in patients treated with N-CSA and intravenous CSA and 24 +/- 15% in patients treated with N-CSA and RATG (P = 0.25). The risk (hazard) of early rejection was higher in the group that received intravenous CSA and N-CSA. CONCLUSIONS: While similar averaged doses of N- and S-CSA were administered early after transplantation, the use of N-CSA resulted in higher blood levels of CSA. N-CSA appears to be well absorbed early after cardiac transplantation, but renal toxicity remains a significant concern.

Administration, Oral↗

[Coronary artery bypass grafting without cardiopulmonary bypass: angiographic evaluation of a preliminary experience].

BACKGROUND: Coronary artery bypass grafting (CABG) without cardiopulmonary bypass has been proposed to decrease morbid events related to the circuit and the blood pump. OBJECTIVE: To evaluate quantitatively coronary anastomoses with CABG without cardiopulmonary bypass. SETTING: Between February and December 1996, 19 patients underwent CABG, through a median sternotomy in 12 patients and an anterior minithoracotomy in seven patients. Twenty internal thoracic artery grafts and seven saphenous vein grafts were studied by quantitative angiography in the immediate postoperative period (4 +/- 2 days). Diameters of native coronary arteries and grafts were analyzed by computer. PATIENTS: Patients averaged 57 +/- 8 years of age, with triple vessel coronary disease in three patients, double vessel disease in nine patients and single vessel disease in seven patients. Twelve patients underwent a single thoracic artery graft to the left anterior descending artery and seven patients underwent a double graft to the anterior descending and the right coronary artery. RESULTS: Hospital stay averaged 5 +/- 2 days, operating time averaged 144 +/- 30 mins and ischemic occlusion of the left anterior descending coronary artery averaged 20 +/- 8 mins. Serum creatine kinase MB fraction averaged 11 +/- 7 U/L and 25 +/- 37 U/L, 1 and 24 h, respectively, after surgery. Diameter stenosis of the native coronary artery averaged 19 +/- 26% proximal to the anastomosis, 36 +/- 31% distal to the anastomosis and 27 +/- 32% at the anastomotic site of internal thoracic artery grafts. One native coronary artery distal to the anastomosis was occluded and an occluded anastomosis was reopened by percutaneous angioplasty 72 h after surgery. Saphenous vein grafted to the right coronary artery had only minimal stenosis at anastomotic sites. CONCLUSION: This initial experience with CABG without cardiopulmonary bypass suggests that adequate coronary anastomosis can be performed in selected patients.

Cardiopulmonary Bypass↗