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Biomedical subjects

R D Weisel

Publications and source records attributed to R D Weisel.

At least 37 records · Page 2Linked to original sources
PubMed1990

Determinants of survival and valve failure after mitral valve replacement.

A prospective evaluation of 333 consecutive patients undergoing isolated mitral valve replacement between 1982 and 1985 was performed to identify the predictors of survival and valve failure. Follow-up between 2 and 6 years postoperatively (mean, 32 +/- 17 months) was 98% complete. Four prostheses were inserted to permit a prospective evaluation of alternative valves: Björk-Shiley mechanical (n = 118), Ionescu-Shiley pericardial (n = 146), Carpentier-Edwards porcine (n = 38), and Hancock pericardial (n = 31). Hospital mortality was 6%, and actuarial survival at 5 years was 74% +/- 5%. Multivariate Cox regression analysis identified advancing age (less than 40 years, 88% +/- 7%; greater than 70 years, 50% +/- 14%) and poor left ventricular function (ejection fraction less than 0.20, 62% +/- 17%; ejection fraction greater than 0.60, 80% +/- 7%) as independent predictors of postoperative survival. Freedom from structural valve dysfunction, prosthetic valve endocarditis, reoperation, and valve-related mortality and morbidity were 86% +/- 4%, 91% +/- 4%, 81% +/- 4%, and 72% +/- 5%, respectively, at 5 years. The actuarial incidence of valve failure was inordinately high with the Hancock pericardial valve (p less than 0.05). Freedom from thromboembolic events (78% +/- 8% at 5 years) was significantly lower in patients with poor ventricular function (ejection fraction (less than 0.20, 54% +/- 20%; ejection fraction greater than 0.60, 73% +/- 11%; p less than 0.05). Survival after mitral valve replacement was determined by age and left ventricular function. Premature failure of the Hancock pericardial valve resulted in an unacceptable rate of valve-related complications.

Adult↗
PubMed1990

Water-soluble antioxidant specificity against free radical injury using cultured human ventricular myocytes and fibroblasts and saphenous vein endothelial cells.

To better understand the protective effect of water-soluble antioxidants against free radical injury to the reperfused ischemic myocardium, we studied the antioxidant effectiveness of superoxide dismutase (SOD), catalase, ascorbic acid, and Trolox, a water-soluble analogue of alpha-tocopherol, in protecting cultured adult human ventricular myocytes and fibroblasts and saphenous vein endothelial cells from hypoxanthine-xanthine oxidase generated free radicals. The cells were cultured at oxygen tension to 150 and 40 mmHg. Passage P2 to P4 cells were injured by a hypoxanthine-xanthine oxidase free radical generation system. The time when all the cells became shriveled divided by the cell count expressed in terms of 100,000 cells was used to compare cellular susceptibilities to free radical injury and the relative effectiveness of the antioxidants. Fibroblasts were more resistant to free radical injury than myocytes which were more resistant than endothelial cells, when all three cell types were cultured at the same oxygen tension. Trolox and ascorbic acid were effective antioxidants for myocytes while SOD and catalase were ineffective. SOD and catalase were more effective than ascorbic acid as antioxidants for endothelial cells and fibroblasts, while Trolox was ineffective. In summary, we have shown that each cultured cell type has a different susceptibility to free radical damage and that antioxidants are not effective for all cell types.

Antioxidants↗
PubMed1990

Dipyridamole for coronary artery bypass surgery.

A randomized trial to compare the effects of oral and intravenous dipyridamole was conducted in 58 patients undergoing coronary artery bypass graft (CABG) surgery. Preoperative oral administration of dipyridamole resulted in lower plasma drug concentrations in the early postoperative period than perioperative intravenous administration. Postoperative platelet counts were highest in the patients receiving intravenous dipyridamole, intermediate in those receiving oral dipyridamole and lowest in the control group. Postoperative blood loss was significantly reduced with both oral and intravenous dipyridamole. A second randomized trial was conducted in an additional 40 patients undergoing CABG surgery to evaluate the effects of dipyridamole on myocardial platelet and leukocyte deposition and the cardiac release of thromboxane. Twenty patients received intravenous dipyridamole perioperatively. Autologous platelets and leukocytes were labeled with 111In and 99mTc respectively and were infused before release of the crossclamp. Myocardial biopsies were obtained after aortic declamping and indicated that platelets and leukocytes were deposited in the myocardium during reperfusion. Dipyridamole reduced both platelet and leukocyte deposition. Cardiac release of thromboxane B2 occurred in the early postoperative period and was reduced by dipyridamole. In conclusion, dipyridamole preserved platelets and reduced postoperative bleeding and blood product transfusions in patients undergoing CABG surgery. Dipyridamole also reduced cardiac platelet deposition and thromboxane release and may reduce perioperative ischemic injury.

Administration, Oral↗
PubMed1990

The cytoprotective effect of Trolox demonstrated with three types of human cells.

Trolox, a hydrophilic analogue of alpha-tocopherol, was reported to scavenge peroxyl radicals better than vitamin E in sodium dodecyl sulfate micelles and in liposomes. However, it was not known if Trolox protects human cells against oxyradical damage or if it acts as an antioxidant there. Here we demonstrate that Trolox prolonged substantially the survival of human ventricular myocytes and hepatocyte against oxyradicals generated with xanthine oxidase plus hypoxanthine, and prevented lysis of red cells exposed to an azo-initiator (2,2'-azo-bis(2-amidinopropane) HCl). Note that Trolox did not inhibit xanthine oxidase. In each cell type, the protection by Trolox was dose dependent and surpassed those given by such water-soluble antioxidants as ascorbic acid, superoxide dismutase, and (or) catalase, each examined at or near its optimal level in the same system. Using hepatocytes as a model, we further observed that Trolox reduced markedly the quantity of phospholipid conjugated dienes (a chemical imprint of oxyradical damage) in cells despite their exposure to oxyradicals. These data suggested that Trolox behaves as an antioxidant in cells as illustrated in hepatocytes.

Antioxidants↗
PubMed1990

Clinical and Doppler echocardiographic evaluation of bioprosthetic valve failure after 10 years.

Four hundred thirteen consecutive patients underwent valve replacement with a bioprosthesis between 1976 and 1982. Aortic valve replacement was performed in 240 patients, mitral valve replacement in 132 patients, and multiple valve replacement in 41. The Carpentier-Edwards porcine (n = 336), Angell-Shiley porcine (n = 23), Hancock porcine (n = 11), and the Ionescu-Shiley pericardial valves (n = 43) were inserted. Follow-up between 5 and 12 years postoperatively was 98% complete. Freedom from structural valve deterioration was 72 +/- 7%, 59 +/- 9%, and 59 +/- 9%, respectively, after aortic, mitral, and double valve replacement. The risk of structural valve deterioration and reoperation for valve-related complications was significantly increased with the Ionescu-Shiley pericardial prosthesis. The risk for reoperation was inversely related to patient age. Postoperative Doppler echocardiographic studies in 87% of available patients revealed a subgroup of asymptomatic patients with evidence of structural valve deterioration. These patients (n = 61) had significantly reduced prosthetic valve areas (aortic less than 1 cm2, mitral less than 1.7 cm2), elevated resting transvalvular gradients (aortic greater than 40 mm Hg), or moderate-to-severe regurgitation. In summary, postoperative Doppler echocardiographic examination identified asymptomatic patients with structural valve dysfunction. These patients must be followed up carefully to determine the optimal timing of reoperation.

Aortic Valve↗
PubMed1990

Right ventricular function and metabolism.

Right ventricular protection may be limited with current methods of cardioplegic delivery. Sensitive measurements of right and left ventricular function and metabolism were made in 30 patients undergoing elective coronary artery bypass surgery with cold cardioplegic arrest. Myocardial adenine nucleotide concentrations decreased with cardioplegia and reperfusion in both the right and left ventricles despite adequate levels of precursors, suggesting perioperative mitochondrial dysfunction. Postoperatively, right and left ventricular pressures were measured with micromanometer catheters and volumes were measured by nuclear ventriculography. Right and left ventricular systolic elastance was calculated by the isochronic method and by the end-systolic method. Both methods provided sensitive indexes of end-systolic elastance. This study demonstrated that right ventricular function and metabolism can be evaluated by methods analogous to methods used in the left ventricle. These results suggest that right ventricular functional and metabolic recovery are delayed despite apparently adequate myocardial protection. Sensitive measurements may permit improved assessment of alternative methods of right ventricular protection.

Adenine Nucleotides↗
PubMed1989

Myocardial salvage with trolox and ascorbic acid for an acute evolving infarction.

Both Trolox (a water-soluble analogue of alpha-tocopherol) and ascorbic acid were more effective than superoxide dismutase or catalase in protecting myocyte cell cultures from free radical attack (induced by hypoxanthine and xanthine oxidase). In a canine model of two hours of left anterior descending coronary artery occlusion followed by four hours of reperfusion, Trolox and ascorbic acid reduced the area of infarction within the area at risk. The Trolox group received 500 mL of deoxygenated saline solution containing 2.0 g of Trolox, 3.0 g of ascorbic acid, and 18 mg of EDTA (ethylenediaminetetraacetic acid) infused into the ascending aorta 30 seconds before and four minutes after reperfusion. Saline controls received 500 mL of deoxygenated saline solution containing 18 mg of EDTA. The angioplasty group had unmodified reperfusion by simple release of the occlusion. The area at risk and the area infarcted were estimated with Evans blue and triphenyl tetrazolium hydrochloride stains, respectively. The ratio of the area infarcted to the area at risk was significantly lower with Trolox (angioplasty, 30.4% +/- 5.1%; saline, 20.8% +/- 2.9%; and Trolox, 8.7% +/- 4.0%; p less than 0.01). In summary, the antioxidants Trolox and ascorbic acid effectively reduced myocardial necrosis after ischemia.

Animals↗
PubMed1989

Effect of oxygen tension on the anti-oxidant enzyme activities of tetralogy of Fallot ventricular myocytes.

Since the chronically cyanotic tetralogy of Fallot (TOF) myocardium is more sensitive to reperfusion injury after cardiac surgery than the adult myocardium, we decided to study the regulation of myocardial superoxide dismutase (SOD), catalase and glutathione peroxidase by oxygen tension. TOF myocytes were cultured at a Po2 of 150 mmHg for 30 days to establish the culture. The cells were then cultured at Po2 of 150 and 40 mmHg and the myocyte antioxidant enzymes measured at days 3, 7, 14 and 21. On day 21 the myocytes cultured at Po2 of 40 mmHg were then cultured at 150 mmHg and SOD and catalase activities measured on days 28 and 35. Although there were no differences in the rates of incorporation of 35S-methionine into the myocytes at either Po2 on these days, the myocytes scavenger enzyme levels were significantly higher by day 14 when cultured at a Po2 of 150 mmHg than at a Po2 of 40 mmHg. With the increase in oxygen tension from 40 to 150 mmHg, SOD and catalase activities increased significantly by day 35. The myocytes cultured at Po2 40 mmHg were more sensitive by day 7 to an hypoxanthine-xanthine oxidase generated free radical injury than the Po2 150 mmHg cultured cells. The regulation of these enzyme activities by oxygen tension and the increased sensitivity to free radical injury of the myocytes cultured at an oxygen tension of 40 mmHg provide putative evidence that the chronically cyanotic myocardium may be less well protected than the normally perfused myocardium against oxygen-mediated free radical injury and be at higher risk for cardiovascular surgery.

Catalase↗
PubMed1989

Delayed myocardial metabolic recovery after blood cardioplegia.

Previous studies have demonstrated that both myocardial metabolism and ventricular function were depressed after blood cardioplegic arrest for elective coronary artery bypass grafting. To evaluate the etiology of this metabolic defect, we measured the levels of adenine nucleotides and their precursors in 29 patients undergoing elective coronary revascularization. Myocardial biopsy specimens were obtained at 37 degrees C before cardioplegic arrest, immediately after 74 +/- 4 minutes of cardioplegic arrest, and after 30 minutes of reperfusion. Biopsy specimens were analyzed for levels of adenine nucleotides and their precursors by high-performance liquid chromatography. Adenosine triphosphate concentrations decreased with cardioplegic arrest and with reperfusion. Adenosine monophosphate concentrations increased after cardioplegic arrest and remained nearly twice the initial values after reperfusion. The ratio of adenosine monophosphate to adenosine triphosphate doubled after reperfusion, suggesting defective conversion of adenosine monophosphate to adenosine triphosphate. Levels of adenine nucleotide degradation products (adenosine, inosine, and hypoxanthine) increased after cardioplegia and decreased with reperfusion, suggesting a washout of soluble precursors. This study suggests that improvements in myocardial protection should attempt to stimulate mitochondrial energy production and preserve adenine nucleotide precursors.

Adenosine Diphosphate↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗