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Biomedical subjects

R D Weisel

Publications and source records attributed to R D Weisel.

At least 55 records · Page 3Linked to original sources

Survival and bioprosthetic valve failure. Ten-year follow-up.

Between 1976 and 1982, 413 consecutive patients underwent valvular replacement with a bioprosthesis. Aortic valve replacement was performed in 240 patients, mitral valve replacement in 132, and multiple-valve replacement in 41. Four prostheses were employed: Carpentier-Edwards porcine (n = 336), Angel-Shiley porcine (n = 23), Hancock porcine (n = 11), and Ionescu-Shiley pericardial (n = 43). Follow-up was conducted between 5 and 12 years postoperatively and was 98% complete. Survival was 65 +/- 4% at 10 years and was independently influenced by advancing age, poor ventricular function, male sex, concomitant coronary artery bypass surgery, and valvular type. The risk of structural valvular dysfunction, reoperation, and any valve-related mortality and morbidity was significantly increased with the Ionescu-Shiley pericardial prosthesis. Long-term survival after valvular replacement was influenced by patient- and valve-related factors. The Ionescu-Shiley pericardial valve had an unusually high incidence of premature failure.

Adult

The changing pattern of coronary artery bypass surgery.

Recent advances in interventional cardiology have altered the profile of patients referred for coronary artery bypass surgery. In recent years, the proportion of high-risk patients has increased dramatically. To evaluate the impact of the changing pattern of surgical patients, we prospectively followed up 7,334 patients who had coronary artery bypass surgery between 1982 and 1986. Multivariate analysis identified the following risk factors for operative mortality: urgency of surgery, left ventricular ejection fraction, age, female sex, previous bypass surgery, and left main coronary artery stenosis. Perioperative mortality has remained stable despite an increasing incidence of high-risk patients. However, perioperative morbidity has increased, due to the large number of high-risk patients. A multivariate analysis was performed by year to identify temporal trends in risk factors. Urgency of surgery, age, and previous bypass surgery have become more significant predictors of mortality with respect to time, whereas female sex, left ventricular ejection fraction, and left main coronary artery stenosis have become less significant determinants of mortality. Our results demonstrate the critical dependence of mortality and morbidity rates on the case mix, and further improvements in the results of coronary artery bypass surgery will require better strategies for the increasing number of high-risk patients.

Age Factors

Valvular surgery in the elderly.

In previous studies from this university, advanced age was identified as an independent predictor of operative mortality for valvular surgery. Therefore, between January 1982 and December 1986, early results were compared in 469 patients greater than 70 years old (Old; 74.0 +/- 3.4 years, mean +/- SD) and in 2,040 patients less than 70 years old (Young; 53.7 +/- 12.1 years). Patients underwent single- or multiple-valve repair or replacement with or without concomitant coronary artery bypass surgery. Data consisting of 31 clinical and angiographic variables were collected prospectively and were analyzed by univariate and multivariate statistics. Old patients were characterized by having more frequent left ventricular dysfunction (left ventricular ejection fraction less than 40%: Old, 33.5%; Young, 22.4%; p less than 0.001), coronary artery disease (Old, 54.5%; Young, 24.2%; p less than 0.001), and urgent surgery (Old, 15.6%; Young, 11.8%; p = 0.02). Aortic valve procedures (Old, 59.7%; Young, 40.1%; p less than 0.001) and concomitant coronary artery bypass surgery (Old, 46.4%; Young, 20.3%; p less than 0.001) were performed more commonly in the Old patient. Operative mortality occurred in 10.0% of Old patients compared with 5.6% of Young patients (p less than 0.001), and major morbidity (low-output syndrome, perioperative myocardial infarction, intra-aortic balloon pump counterpulsation, and stroke) occurred significantly more frequently (p less than 0.001) in the Old. Stepwise logistic regression identified that urgent operation (p = 0.002), mitral or double-valve surgery (p = 0.004), coronary artery disease especially when not treated by bypass surgery (p = 0.02), female gender (p = 0.02), and left ventricular dysfunction (p = 0.05) independently predicted operative death in the Old population. The significant predictors of mortality in the Young patient were urgent operation (p less than 0.001), New York Heart Association class IV (p less than 0.001), associated tricuspid valve disease (p = 0.002), decreased left ventricular function (p = 0.01), valvular re-replacement (p = 0.02), and increasing age (p = 0.03). The predicted probability of operative mortality in Old patients ranged between 0.9 +/- 0.5% and 76 +/- 16%. Elderly patients in good risk categories should be offered surgical intervention for correction of valvular lesions. Alternative therapy may be indicated in patients with multiple risk factors.

Age Factors

Myocardial free-radical injury after cardioplegia.

Although cold blood cardioplegia provides excellent myocardial protection for elective coronary bypass surgery, myocardial metabolic recovery is delayed postoperatively, perhaps because of free-radical injury during reperfusion. To assess free-radical reperfusion injury, we measured the products of lipid peroxidation and the cardiac concentrations of alpha tocopherol in 10 patients undergoing elective surgical revascularization. Arterial and coronary sinus blood measurements revealed a delayed recovery of myocardial oxygen consumption and lactate utilization and the myocardial release of conjugated dienes (chemical signatures of free-radical injury) at 3 and 60 minutes after reperfusion. In addition, myocardial concentrations of alpha tocopherol decreased after reperfusion, suggesting consumption of the major membrane antioxidant. These results support the hypothesis that oxygen-derived free radicals contribute to myocardial injury after cardioplegic arrest and that antioxidant therapy should improve myocardial protection.

Free Radicals

Effects of anesthetic induction on myocardial function and metabolism: a comparison of fentanyl, sufentanil and alfentanil.

Anaesthetic induction may induce myocardial ischaemia. A prospective randomized trial was instituted to compare the effect on ventricular function and myocardial metabolism of induction with fentanyl (FEN) or its analogues sufentanil (SUF) or alfentanil (ALF) in 96 patients undergoing elective coronary artery bypass grafting (CABG). Haemodynamic, metabolic (coronary sinus oxygen and lactate extraction) and gated ventriculographic measurements were made awake pre-induction (PRE), after induction (IND) and after intubation (INT). Induction was performed with FEN 75 micrograms.kg-1, SUF 15 micrograms.kg-1 or ALF 125 micrograms.kg-1 and metocurine. Fentanyl induction was associated with the greatest stability of mean arterial pressure (MAP), cardiac performance, and systolic function without associated myocardial lactate production. SUF produced the greatest depression of systolic function (p less than 0.05) but without haemodynamic instability or myocardial lactate production in all but one patient. Induction with ALF produced the greatest reduction in MAP (p less than 0.05) associated with the greatest decrease in diastolic compliance (p less than 0.05) and 50 per cent incidence of myocardial lactate production (p less than 0.05) with no significant change in coronary blood flow or myocardial oxygen consumption.

Alfentanil

Decreased postoperative myocardial fatty acid oxidation.

Myocardial substrate preferences following cardioplegic arrest for coronary bypass surgery have not been established. Fatty acids are believed to be the major fuel source for aerobic metabolism. Following cardioplegic arrest arterial fatty acid levels are elevated and myocardial fatty acid accumulation without oxidation may contribute to reperfusion injury. Perioperative fatty acid metabolism was evaluated in 18 patients undergoing elective coronary bypass surgery who were randomized to receive either blood (n = 11) or crystalloid (n = 7) cardioplegia. Palmitate labeled with 14carbon was infused perioperatively and arterial and coronary sinus blood samples were obtained to calculate myocardial fatty acid extraction and oxidation before and after cardioplegic arrest. Lactate and glycerol were released from the heart during both blood and crystalloid cardioplegia, suggesting ischemic glycolysis and lipolysis. Myocardial oxygen consumption was depressed and the myocardial consumptions of lactate, glucose, and fatty acids were minimal during the first 60 min after aortic clamp removal in both groups despite high arterial concentrations. Fatty acid oxidation was minimal after blood cardioplegia and was not found after crystalloid cardioplegia. Fatty acids were extracted by the heart, but were not aerobically metabolized following cardioplegic arrest. Myocardial fatty acid accumulation without oxidation may have been deleterious. The inability of the heart to oxidize exogenous fatty acids may reflect altered myocardial exogenous substrate preferences during reperfusion following coronary bypass surgery.

Cardioplegic Solutions

Technique of successful clinical double-lung transplantation.

Lung transplantation has become a successful method in the therapy for end-stage pulmonary disease. While single-lung transplantation provides benefit to patients with pulmonary fibrosis, bilateral lung transplants are required for septic or emphysematous lung disease. We describe the technique employed in 6 patients to transplant en bloc both lungs with the recipient heart left in place. The lungs are connected by a left atrial cuff, main pulmonary artery, and trachea. The completed implantation has a tracheal anastomosis securely wrapped in omentum, a left atrial anastomosis posterior to the heart, and a pulmonary artery anastomosis anteriorly. Airway ischemia resulted in the death of 1 patient. This procedure allows complete excision of all diseased pulmonary tissue, retention of the recipient's own heart, and separate excision of the donor heart for use in another recipient, thereby markedly increasing the supply of donor lungs for transplantation.

Adolescent

Myocardial performance after repair of congenital cardiac defects in infants and children. Response to volume loading.

The hemodynamic response to increasing left atrial pressure by volume loading was evaluated in 70 children during the first 24 hours after repair of congenital cardiac defects. The children were grouped into four diagnostic categories: atrial septal defect or pulmonary valve stenosis (n = 8), ventricular septal defect (n = 36), complete transposition after Mustard's operation (n = 13), and tetralogy of Fallot (n = 13). Within 2 hours of bypass, both cardiac index and left ventricular stroke work index were adequate and increased appropriately with volume loading in all four diagnostic groups. The atrial septal defect group demonstrated a similar response to volume loading 4 and 24 hours after bypass. However, the other three diagnostic groups had a higher filling pressure, lower cardiac index and stroke work index, and a depressed response to increasing preload 4 hours postoperatively, which indicated a deterioration in cardiac performance. The deterioration was maximal between 4 and 12 hours after bypass, and performance tended to recover 24 hours postoperatively. The transposition group had a more profound depression in cardiac performance than the other two groups. Within the ventricular septal defect group, smaller children (body surface area less than 0.36 m2) had a more profound depression in performance than larger children. These results demonstrate a significant alteration in cardiac performance during the first 24 hours after repair of congenital cardiac defects in children. These changes should be considered when postoperative management is being planned.

Cardiac Output

Inadequate myocardial protection with cold cardioplegic arrest during repair of tetralogy of Fallot.

Postoperative low cardiac output is the most common cause of death in patients undergoing elective repair of tetralogy of Fallot. The incidence is much higher than in elective adult bypass operations for coronary artery disease. To explain this difference, we investigated 16 children having elective repair of tetralogy (mean age 6.3 years). Myocardial biopsy specimens obtained during bypass before arrest, at the end of cold arrest by blood cardioplegia, and after 30 minutes of reperfusion were studied for adenosine triphosphate and lactate levels. Myocardium was submitted for microscopic study shortly after the onset of ischemia. The operation was successful in reducing right ventricular-pulmonary artery gradients from 82 +/- 28 to 9 +/- 1 mm Hg, yet seven patients required significant inotropic support (dopamine, greater than 5 micrograms/kg/min) for more than 24 hours and 12 patients needed prolonged use of digoxin and diuretics for right ventricular failure. Tissue levels of adenosine triphosphate and lactate in the tetralogy groups were compared with those in 20 adults with coronary artery disease having similar myocardial protection techniques. Adenosine triphosphate levels in the tetralogy group decreased during cross-clamping (41 +/- 8 minutes) from 24 +/- 3 to 16 +/- 2 mmol/kg dry weight (mean +/- 1 standard error), with a marked further drop after reperfusion to 9 +/- 2 mmol/kg (p less than 0.01). Adenosine triphosphate levels in the group with coronary disease also decreased from 20 +/- 1 to 16 +/- 1 mmol/kg after a longer cross-clamp time (70 +/- 17 minutes) but remained at 15 +/- 2 mmol/kg after reperfusion. Tissue lactate levels in the tetralogy group rose markedly during ischemia and remained elevated after reperfusion. In contrast, lactate levels in the group with coronary disease rose moderately during ischemia and returned to normal early on reperfusion. Microscopic study revealed focal myocyte necrosis in tetralogy of Fallot. Our findings, which demonstrate inadequate myocardial protection of patients with tetralogy during repair, with depression of adenosine triphosphate and increased lactate during ischemia and reperfusion, suggest a defect in oxidative metabolism. The drop in adenosine triphosphate after reperfusion in the patients with tetralogy implicates reperfusion injury as a mechanism of myocardial damage.

Adenosine Triphosphate

Right and left ventricular metabolites.

Current methods of cardioplegic delivery may delay the recovery of right ventricular metabolism and function. To evaluate right and left ventricular metabolism, we performed biopsies in 37 patients undergoing elective coronary bypass operation with aortic root blood cardioplegia. Right ventricular temperatures were warmer than left ventricular temperatures during cardioplegic arrest (right ventricle: 16.8 degrees +/- 3.8 degrees C, left ventricle: 14.3 degrees +/- 3.7 degrees C, p = 0.02). Adenosine triphosphate concentrations were lower in the right ventricle than in the left ventricle before cardioplegic arrest (right ventricle: 13.8 +/- 7.8 mmol/kg, left ventricle: 21.5 +/- 8.7 mmol/kg, p = 0.02). After reperfusion, right ventricular adenosine triphosphate concentrations fell to low levels (10 +/- 6 mmol/kg). Postoperative left and right ventricular high energy phosphate concentrations (the sum of adenosine triphosphate and creatine phosphate levels) correlated inversely with myocardial temperatures during cardioplegia (r = -0.29, p = 0.048). Aortic root cardioplegia did not cool the right ventricle as well as it did the left ventricle. The lower preoperative high energy phosphate concentrations may have increased the susceptibility of the right ventricle to ischemic injury. Alternative methods of myocardial preservation may improve right ventricular cooling and protection.

Adenosine Triphosphate

Improving myocardial metabolic and functional recovery after cardioplegic arrest.

The myocardial oxidation of fatty acids and glucose, the predominant substrates for aerobic metabolism, is impaired after cardioplegic arrest for coronary revascularization. Because lactate can be readily metabolized to pyruvate, it may be the preferred substrate for aerobic metabolism after cardioplegic arrest when arterial concentrations are elevated. Nineteen patients undergoing elective coronary revascularization with blood cardioplegia were randomized to receive LOW (nine patients, no exogenous lactate) or HIGH (10 patients, a perioperative infusion of Ringer's lactate) arterial lactate concentrations. Coronary sinus catheterization and lactate labeled with carbon 14 permitted calculation of myocardial oxygen consumption and lactate oxidation which were significantly increased during reperfusion in the group with HIGH arterial lactate concentrations. Atrial pacing at 110 beats/min on cardiopulmonary bypass resulted in myocardial lactate production (suggesting ischemic anaerobic metabolism) in the LOW lactate group, but atrial pacing increased lactate consumption and oxidation in the HIGH lactate group (suggesting increased aerobic metabolism). Systolic function (the relation between end-systolic pressure and volume) as assessed by nuclear ventriculography 3 hours postoperatively was significantly better (p less than 0.05 by analysis of covariance) in the HIGH lactate group. Postoperative myocardial creatine kinase release was significantly lower in the HIGH lactate group, which suggested less perioperative ischemic injury. Lactate was the preferred substrate for myocardial oxidative metabolism after cardioplegic arrest, and the higher arterial lactate concentrations improved myocardial metabolic and functional recovery and reduced perioperative ischemic injury.

Cardiac Pacing, Artificial

Postoperative hypertension: a comparison of diltiazem, nifedipine, and nitroprusside.

In previous studies, the treatment of postoperative hypertension with sodium nitroprusside induced ischemic metabolism without a decrease in coronary sinus blood flow. In contrast, the calcium antagonists diltiazem and nifedipine reduce blood pressure and may improve myocardial metabolism. A prospective randomized trial was performed in 62 patients, in whom hypertension developed (mean arterial pressure greater than 95 mm Hg) after coronary bypass procedures, to compare diltiazem (n = 22), nifedipine (n = 20), and nitroprusside (n = 20). All three agents reduced blood pressure equally (p less than 0.0001, by analysis of variance). Heart rate decreased with diltiazem (p = 0.006) but increased with nifedipine and nitroprusside (p less than 0.05). Left ventricular diastolic function (the relation between left atrial pressure and left ventricular end-diastolic volume) was not changed with the three drugs. Systolic function (the relation between systolic blood pressure and left ventricular end-systolic volume) was depressed with diltiazem (p = 0.05 by analysis of covariance) and nifedipine (p = 0.05) but not with nitroprusside. Myocardial performance (the relation between left ventricular stroke work index and end-diastolic volume) was depressed most by diltiazem (p = 0.001 by analysis of covariance), and to a lesser extent with nifedipine (p = 0.03), but not with nitroprusside. Myocardial lactate flux in response to the stress of atrial pacing decreased with nitroprusside but not with diltiazem or nifedipine (p = 0.03 by analysis of variance). Diltiazem and nifedipine are effective agents for treating postoperative hypertension after coronary artery bypass operations.

Clinical Trials as Topic

Dipyridamole preserved platelets and reduced blood loss after cardiopulmonary bypass.

Cardiopulmonary bypass activates and depletes platelets, which may contribute to postoperative bleeding. In addition, activated platelets may be deposited in the coronary vasculature after ischemia and cardioplegia, which may delay recovery of cardiac function and metabolism and may contribute to early bypass graft occlusion. The antiplatelet agent dipyridamole reduces platelet activation and depletion and may decrease postoperative bleeding and transfusion requirements. A prospective randomized trial was conducted in 58 patients undergoing elective coronary bypass operations to compare the effects of oral (19 patients) and intravenous (21 patients) dipyridamole to the results obtained in a control group (18 patients) who received no dipyridamole. Preoperative oral administration of dipyridamole resulted in lower plasma drug concentrations in the early postoperative period than perioperative intravenous administration (p = 0.0001 by analysis of variance). Postoperative arterial platelet counts were highest in the patients receiving intravenous dipyridamole, intermediate in those receiving oral dipyridamole, and lowest in the control group (p = 0.03 by analysis of variance). Postoperative blood loss and blood product transfusions were significantly reduced with both oral and intravenous dipyridamole (p = 0.04 by analysis of variance). Dipyridamole preserved platelets and reduced postoperative bleeding. Intravenous dipyridamole resulted in higher platelet counts than oral dipyridamole and may be required to reduce postoperative bleeding in high-risk patients.

Administration, Oral

Predictors of operative survival after valve replacement.

To identify the independent predictors of operative mortality, we examined 31 preoperative clinical and hemodynamic variables in 2,488 patients undergoing valvular surgery between 1982 and 1986. The operative mortality was 5.3% in 1,098 patients after aortic valve surgery, 6.6% in 1,107 after mitral valve surgery, and 10.1% in 283 after double valve surgery. Multivariate statistical analysis demonstrated that urgent surgery, endocarditis requiring urgent surgery, previous aortic valve surgery, coronary artery disease, and age were independent risk factors for aortic valve surgery. Urgent surgery, endocarditis, age, coronary artery disease, and preoperative ventricular ejection fraction were independent predictors of mortality after mitral valve surgery. The predictors of mortality after double valve surgery were urgent surgery, age, preoperative ventricular ejection fraction, and tricuspid valve disease. Gender and the type of valvular lesion, procedure, and prosthesis did not independently influence operative mortality. Strategies to diminish operative mortality should include careful assessment of the risks and benefits in elderly patients, early operative intervention before deterioration that necessitates urgent surgery, and use of improved techniques of myocardial protection in high-risk subgroups.

Adult

Dipyridamole reduced myocardial platelet and leukocyte deposition following ischemia and cardioplegia.

Urgent coronary revascularization for acute myocardial ischemia results in an increased mortality and morbidity. Deposition of activated platelets and leukocytes into the ischemic myocardium during reperfusion may augment perioperative ischemic injury. Dipyridamole reduces platelet activation and may reduce myocardial deposition and prevent ischemic injury during reperfusion. The effects of dipyridamole on myocardial platelet and leukocyte deposition were evaluated in a canine model of acute regional myocardial ischemia with reperfusion during cardioplegia on cardiopulmonary bypass. Eight dogs underwent left anterior descending (LAD) coronary artery ligation for 45 min followed by cardiopulmonary bypass and release of the ligature during 60 min of cold crystalloid cardioplegic arrest to simulate urgent revascularization. Four dogs were randomized to receive an infusion of dipyridamole perioperatively (50 mg/hr) and 4 dogs served as controls. Autologous platelets were labeled with 111In, leukocytes with 99mTc, and erythrocytes with 51Cr. The labeled cells were infused immediately after cross-clamp release and myocardial biopsies were obtained at 10, 20, 30, and 60 min of reperfusion. Platelets were deposited in the myocardium during reperfusion and four times more platelets were found in the LAD region than the circumflex region. Leukocyte deposition was similar in the LAD and circumflex regions. Dipyridamole reduced both platelet and leukocyte deposition and the reduction was greater in the LAD than in the circumflex region. Myocardial platelet and leukocyte deposition was found after regional ischemia, cardioplegia, and cardiopulmonary bypass. Dipyridamole reduced myocardial platelet and leukocyte deposition and may reduce perioperative ischemic injury.

Animals

Right ventricular function: a comparison between blood and crystalloid cardioplegia.

Blood cardioplegia resulted in better left ventricular (LV) function than crystalloid cardioplegia after elective coronary artery bypass operations. However, most methods of cardioplegic delivery may not adequately cool and protect the right ventricle, and right ventricular (RV) dysfunction may limit hemodynamic recovery. Therefore, RV and LV temperatures were measured intraoperatively and RV and LV function were evaluated postoperatively in 80 patients with double-vessel or triple-vessel coronary artery disease who were randomized to receive either blood cardioplegia or crystalloid cardioplegia. Myocardial performance, systolic function, and diastolic function were assessed with nuclear ventriculography by evaluating the response to volume loading. Preoperatively the groups were similar. Intraoperatively, blood cardioplegia resulted in significantly warmer LV and RV temperatures (left ventricle: 15.5 degrees +/- 0.2 degrees C with blood cardioplegia and 12.6 degrees +/- 0.3 degrees C with crystalloid cardioplegia [p less than .0001]; right ventricle: 18.3 degrees +/- 0.3 degrees C with blood cardioplegia and 15.1 degrees +/- 0.3 degrees C with crystalloid cardioplegia [p less than .0001]). Postoperatively, blood cardioplegia resulted in better LV performance (higher LV stroke work index at a similar LV end-diastolic volume index [EDVI]) (p = .01), better LV systolic function (similar systolic blood pressures at smaller LV end-systolic volume indexes [ESVI]), (p = .04), and improved LV diastolic function (lower left atrial pressures at similar LVEDVIs) (p = .03).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure