Biomedical subjects

R D Weisel

Publications and source records attributed to R D Weisel.

At least 73 records · Page 4Linked to original sources

PubMed1994

Optimal flow rates for retrograde warm cardioplegia.

Retrograde delivery of warm blood cardioplegia may improve nutrient cardioplegic flow beyond coronary obstructions, but may not adequately perfuse the right ventricle and the posterior left ventricle. To determine the optimal flow rate for warm retrograde cardioplegia, we assessed 62 patients undergoing elective coronary artery bypass in two studies. In the low flow study, administration of 50 ml/min (n = 9), 75 ml/min (n = 11), or 100 ml/min (n = 7) was associated with high lactate production and oxygen extraction during cardioplegic administration. At 50 minutes of cardioplegic arrest, the coronary venous effluent pH was low in all groups. In the high flow study, 30 patients all received flow rates of 100, 200, and 300 ml/min in randomized order during the crossclamp period. In addition, five patients received cardioplegia at a rate of 500 ml/min for the duration of the crossclamp period. Administration of 200 ml/min or higher minimized lactate production and maintained coronary venous pH within the physiologic range, but flows of 300 ml/min or higher did not increase oxygen use or reduce lactate or acid production. Patients in the low flow groups had significantly greater myocardial lactate release during cardioplegic infusion and after removal of the crossclamp than the high flow group. Warm retrograde cardioplegia should be delivered at flow rates of at least 200 ml/min during elective coronary artery bypass operations.

Adult↗

PubMed1993

Identification of oxygen responsive elements in the 5'-flanking region of the human glutathione peroxidase gene.

The -1389 to +588 region of the human genomic glutathione peroxidase gene (hgpx1) was amplified using the polymerase chain reaction. This DNA fragment was cloned and sequenced, and various deletion constructs derived from the hgpx1 5'-flanking region were fused to the chloramphenicol acetyltransferase gene. These reporter genes were analyzed in transient transfection assays using primary cultured human ventricular cardiomyocytes obtained from patients with tetralogy of Fallot. Two distinct regions upstream from the transcription start site, which was determined using S1 nuclease analysis, were identified to be responsive to the oxygen tension in culture (pO2 values of 150 or 40 mm Hg). Methylation interference footprinting assays revealed proteins closely apposed to two sequences located at -1232 to -1213 and -282 to -275. We have designated these oxygen responsive elements ORE1 and ORE2, respectively. Gel mobility shift assays using double-stranded oligonucleotides corresponding to each site have demonstrated the formation of specific complexes using both cultured human cardiomyocyte and HeLa nuclear extracts. ORE1 and ORE2 bind disparate proteins with equal precision as bound complexes could be competed away with identical sequences but not with either the other ORE or an unrelated sequence. Insertion of these oxygen responsive elements into a reporter gene governed by a SV40 promoter similarly regulated chloramphenicol acetyltransferase activity according to the oxygen tension in culture.

Base Sequence↗

PubMed1993

Effect of sodium tanshinone IIA sulfonate in the rabbit myocardium and on human cardiomyocytes and vascular endothelial cells.

Sodium tanshinone IIA sulfonate (STS) is a derivative of tanshinone IIA. The latter is a pharmacologically active component isolated from the rhizome of the Chinese herb Salvia miltiorrhiza. Liquid chromatographically pure STS was found to reduce myocardial infarct size by 53.14 +/- 22.79% relative to that in the saline control in a rabbit 1 hr-ischemia and 3 hr-reperfusion model. This effect was comparable to that of Trolox (a better characterized antioxidant serving as a reference cytoprotector), which salvaged the myocardium in the same infarct model by 62.13 +/- 18.91%. Also, like Trolox, STS did not inhibit oxygen uptake by xanthine oxidase (XO), a key enzyme in free radical generation. However, in contrast to Trolox, STS significantly prolonged the survival of cultured human saphenous vein endothelial cells but not human ventricular myocytes in vitro when these cells were separately exposed to XO-generated oxyradicals. Note that the endothelium is recognized to be a key site of oxidant generation and attack. Our findings in vitro and in vivo support the interpretation that STS is a cardioprotective substance, and that it may exert a beneficial effect on the clinically important vascular endothelium.

Animals↗

PubMed1993

Comparison of two experimental models for assessment of cardiac preservation.

Previous studies from this institution using human cell cultures have suggested that University of Wisconsin solution is preferred for prolonged hypothermic storage for cardiac transplantation. The primary objective of this study was to evaluate the effectiveness of extended cardiac preservation with University of Wisconsin solution by assessing the time-related changes of purine metabolites using two different models of cold storage. Isolated rat hearts (n = 6/group) or human ventricular myocyte cultures (n = 7 dishes/group) were assessed after 0, 6, 12, and 24 hours in University of Wisconsin solution at 0 degrees C using high-performance liquid chromatography. Adenosine triphosphate content decreased from 18.1 +/- 5.4 to 9.6 +/- 2.7 mumol/g dried weight by 12 hours and to 1.0 +/- 0.6 mumol/g by 24 hours (p < 0.0001 by analysis of variance) in the rat model. Adenosine triphosphate content decreased from 0.64 +/- 0.42 to 0.14 +/- 0.11 nmol/micrograms DNA at 6 hours and to 0.04 +/- 0.03 nmol/micrograms DNA by 24 hours (p < 0.00001) in the cardiomyocytes. Inosine monophosphate content increased from 0.1 +/- 0.2 to 10.8 +/- 1.0 by 24 hours (p < 0.0001) in the rat studies. Inosine monophosphate values tended to increase up to 12 hours (p = 0.06) in the cell cultures and then declined. Adenosine concentration increased from 0.3 +/- 0.3 to 2.3 +/- 0.9 mumol/g at 6 hours and declined thereafter (p < 0.0005) in the rodent hearts. Adenosine concentration increased from 0.03 +/- 0.02 to 1.53 +/- 0.72 nmol/micrograms DNA at 6 hours (p < 0.0001) in the cardiomyocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1993

Which techniques of cardioplegia prevent ischemia?

One hundred seven patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (n = 21), warm retrograde (n = 22), cold antegrade (n = 20), cold retrograde (n = 22), or intermittent cold antegrade (n = 22) blood cardioplegia. Myocardial oxygen consumption and lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during the operation, and creatine kinase-MB release was assessed postoperatively. Warm cardioplegia resulted in greater myocardial lactate production than cold cardioplegia (p = 0.048). Retrograde cardioplegia was associated with greater lactate production than antegrade cardioplegia (p = 0.015). Adenosine triphosphate depletion was similar among groups. However, poorly diffusible metabolites of adenosine triphosphate accumulated to the greatest extent in the intermittent cold group. Levels of hypoxanthine were highest after warm retrograde cardioplegia. Operative mortality and morbidity were low and were not different among groups. In summary, none of the five techniques of cardioplegia evaluated in this study was able to completely prevent myocardial ischemia. Anaerobic lactate production was minimized with cold cardioplegia and with antegrade cardioplegic delivery. Hypothermia may have impaired regeneration of adenosine triphosphate, however, particularly in association with inadequate or intermittent cardioplegic flow.

Adenosine Monophosphate↗

PubMed1993

Prevention of postbypass bleeding with tranexamic acid and epsilon-aminocaproic acid.

In this institution, two antifibrinolytic agents have been in routine use before cardiopulmonary bypass (CPB) to prevent bleeding due to fibrinolysis; epsilon-aminocaproic acid (EACA) or tranexamic acid (TA) are administered as intravenous infusions over 2 hours, from the time of anesthetic induction until the onset of CPB. TA is 10 times more potent and binds more strongly to plasminogen than EACA. Data were collected retrospectively on 411 patients undergoing first-time coronary artery bypass grafting with cardiopulmonary bypass who had received one of four therapy regimens: 10 g of EACA (65 patients), 15 g of EACA (60 patients), 6 g of TA (100 patients), or 10 g of TA (75 patients). Patients who did not receive any drug (91) served as controls. Anesthetic technique and the heparin/protamine protocol did not differ. Blood collected by mediastinal and pleural tubes was autotransfused up to 6 hours postoperatively. Both TA and EACA reduced post-CPB bleeding in the first 24 hours. Ten grams of TA was the most effective, resulting in a 52% and 36% reduction in blood loss over controls at 6 and 24 hours, respectively. Although 10 g of TA was more effective than 6 g of TA in blood loss control for the first 6 hours, the difference was not significant at 24 hours. A significantly lower number of patients in the 10 g TA group received blood products than in control (28% v 49%) patients (P = 0.02). Pretreatment with 10 g of TA prevented excessive (over 750 mL in 6 hours) bleeding after CPB.

Aminocaproic Acid↗

PubMed1993

Myocardial stunning after coronary bypass surgery.

At the Toronto Hospital, 2,510 patients received isolated coronary bypass grafts (CABG). Overall mortality was 2.3%, the incidence of low output syndrome (as defined by need for inotropic agents or intraaortic balloon pump) was 9.2%, and mortality among low output syndrome patients was 16%. We have attempted to identify factors that minimize cardiac injury. We have previously shown that free radical injury occurs during CABG: coronary blood contains increased levels of conjugated dienes after cross-clamp release; and, there is a reduction in the antioxidant, alpha-tocopherol. In vitro studies revealed that ascorbic acid and alpha-tocopherol protect cardiac myocytes, while endothelial cells are protected from free radical injury by superoxide dismutase and catalase. To test the former two antioxidants in vivo, we used left anterior descending artery (LAD) occlusion in the dog followed by 2 to 4 hours of reperfusion. When administered in deoxygenated saline at 30 seconds prior to reperfusion and 4 minutes after release of LAD occlusion, both agents significantly reduced the infarction area compared to simple reperfusion or deoxygenated saline alone. Antioxidants therefore have the potential to reduce the ischemic injury and myocardial stunning that accompany CABG.

Animals↗

PubMed1993

Models of myocardial stunning.

The use of animal models is a valuable approach to the elucidation of the pathophysiology of myocardial stunning. Coronary occlusion followed by reperfusion produces stunning experimentally, mimicking a myocardial infarction followed by thrombolysis, angioplasty, or coronary bypass. Timing of occlusion and duration to avoid necrosis is critically dependent on the animal species used. For example, 10 minutes of occlusion is required in pigs, 20 minutes in canine models, and sheep or rabbits may require ischemic times somewhere in between. Alternatively, two to six cycles of occlusion followed by reperfusion (repetitive occlusion) may be used. In addition, global ischemia with the heart vented and on cardiopulmonary bypass may simulate myocardial stunning. In this case, 30 minutes produces 50% reductions in myocardial contractility in dogs while 10 minutes is needed in pigs. Animal models have also included the study of a stunned heart in an in vitro apparatus. In these models, discontinuation of perfusion for 10 to 15 minutes is needed to produce stunning in rats, 20 minutes in rabbits, and probably longer periods in dogs and pigs. Myocyte cell cultures may also be valuable for studying responses to ischemia and reperfusion at the cellular level. It is generally agreed that cardioplegic protection, antioxidants, metabolic enhancements, and blockade of calcium overload are some of the strategies that can minimize or eliminate myocardial stunning.

Animals↗

PubMed1993

Ventricular function after normothermic versus hypothermic cardioplegia.

Warm cardioplegia produced by essentially continuous infusion has been used as an alternative to traditional cold intermittent infusion techniques during cardiac surgery, but its effects on postoperative left ventricular function have not been defined. We performed a randomized clinical trial to assess the effects of warm and cold blood cardioplegia on load-independent indices of ventricular function. Fifty-three patients were randomized to warm (n = 27) or cold (n = 26) cardioplegia. Myocardial oxygen consumption, lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during cardioplegia and reperfusion. In 13 patients per group, pressure-volume loops were constructed and ventricular function was assessed 3 hours after the operation. Warm cardioplegia resulted in greater myocardial lactate production but improved recovery of oxygen consumption during reperfusion. Depletion of adenosine triphosphate was similar between groups, but total adenine nucleotides (adenosine triphosphate + adenosine diphosphate + adenosine monophosphate) fell further during warm cardioplegia. Cold cardioplegia was associated with an accumulation of adenosine diphosphate and adenosine monophosphate. Creatine kinase MB isoenzyme release was reduced in the warm group. Three hours after the operation, end-systolic elastance and preload-recruitable stroke work index were increased after warm cardioplegia, and early diastolic relaxation was also increased. Increased systolic function after warm cardioplegia may have been related to improved myocardial protection, elevated arterial lactate concentrations, or increased circulating catecholamine levels. Altered diastolic compliance in the warm group may reflect greater active relaxation during early diastolic filling.

Adenine Nucleotides↗

PubMed1992

Production and reversibility of right ventricular hypertrophy and right heart failure in dogs.

Combined heart-lung transplantation has been used for end-stage primary pulmonary hypertension. Experience with single-lung transplantation for other conditions suggested that associated severe right ventricular dysfunction resulting from increased afterload would recover after placement of a satisfactory lung allograft. Early experience with the application of single-lung transplantation for pulmonary hypertension supports this contention. We devised a reversible canine model of chronic progressive pressure-overloaded right heart failure by pulmonary artery banding to study the echocardiographic, hemodynamic, and pathological reversibility of the failing right heart. Clinical right heart failure was defined as the development of ascites and pleural effusions. Right heart failure developed in 23 dogs 67 to 348 days after banding, and they were divided into two groups to determine its early and long-term effects. Group 1 dogs (n = 11) were either sacrificed immediately after the onset of right heart failure (n = 5) or unbanded (n = 6); group 2 dogs (n = 12) were maintained in right heart failure for 3 months and then either sacrificed (n = 6) or unbanded. Unbanded dogs in both groups were observed for 4 additional months before sacrifice. A control group of 6 normal dogs was sacrificed for pathological comparisons. After unbanding, the right ventricular systolic pressure fell from 97 +/- 17 mm Hg (group 1) and 88 +/- 31 mm Hg (group 2) to 44 +/- 11 mm Hg and 47 +/- 13 mm Hg, respectively. Despite this persistent gradient across the pulmonary artery, echocardiographic and hemodynamic measures of right ventricular function returned to normal, albeit more slowly in the group 2 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The regulation of glutathione peroxidase gene expression by oxygen tension in cultured human cardiomyocytes.

In earlier studies we have shown that the activity of the antioxidant enzyme glutathione peroxidase is regulated by oxygen tension in cultured tetralogy of Fallot (TOF) ventricular myocytes and in the ventricles of TOF patients having corrective cardiac surgery. The present study was undertaken to determine the mechanism of this regulation. Northern and slot blot analysis was performed using RNA isolated from TOF myocytes cultured at oxygen tensions of 150 and 40 mmHg for 3, 7, 14, 21, and 28 days. As was found for enzyme activities, glutathione peroxidase mRNA levels were lower in the cells cultured at a pO2 of 40 mmHg than at 150 mmHg and could be elevated with an increase in oxygen tension. These results were standardized against house-keeping gene hexosaminidase B which showed no difference in mRNA levels between the two oxygen tensions throughout the time course. Nuclear run-off assays indicated that glutathione peroxidase was regulated by oxygen tension at the transcriptional level, while hexosaminidase B and total mRNA synthesis levels remained unchanged.

Adult↗

PubMed1992

Prolonged hypothermic cardiac storage for transplantation. The effects on myocardial metabolism and mitochondrial function.

Cardiac storage for transplantation is currently limited to 6 hours. To better understand the metabolic changes that occur during hypothermic (4 degrees C) storage, we monitored the morphologic and metabolic changes in the canine myocardium at 0, 12, and 24 hours of storage in University of Wisconsin solution. Attempts to isolate cardiac mitochondria resulted in a progressive decline in the yield (milligrams of mitochondria per gram of heart tissue), which decreased (p less than 0.05) from 9.2 +/- 0.4 at 0 hours (control) to 4.0 +/- 0.3 after 12 hours and further decreased (p less than 0.05) to 1.9 +/- 0.2 after 24 hours of cold storage. Mitochondrial state 3 respiration fell to 64% of control after 12 hours and 28% of control after 24 hours of cold storage (p less than 0.05). Citrate synthetase activity, but not cytochrome C oxidase activity, was significantly depressed after 12 and 24 hours of cold storage. Adenosine triphosphate content decreased to 67% of control after 12 hours and 50% of control after 24 hours. After 12 hours of storage, sufficient adenosine diphosphate and monophosphate were present to permit some restoration of adenosine triphosphate, provided mitochondrial function was normal after transplantation. However, restoration of mitochondrial function and adenosine triphosphate levels sufficient to support myocardial contractility was unlikely after 24 hours of storage. This study suggests that a return of adequate cardiac function after transplantation may be possible after 12 hours of cold storage in University of Wisconsin solution but not after 24 hours of cold storage.

Adenosine Triphosphate↗

PubMed1992

In vitro assessment of the effects of glucose added to the University of Wisconsin solution on myocyte preservation.

BACKGROUND: University of Wisconsin solution (UWS) has been successfully used for liver transplantation and may be beneficial for hypothermic cardiac storage. The addition of glucose may enhance myocardial preservation. METHODS AND RESULTS: Cultured human ventricular myocytes (eight dishes per group) were stored at 0 degree C for 12 hours in either unmodified UWS or UWS with glucose (1, 3, 10, 30, or 100 mmol/l). Cells were assayed for protein by spectrofluorometry and adenine nucleotides by high performance liquid chromatography after storage. Protein recovery, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and total adenine nucleotides (ATP+ADP+AMP) were all depleted after storage (p < 0.0001 by ANOVA). Protein recovery (p < 0.005), ATP (p < 0.05), and ADP (p < 0.05) were increased with glucose administration compared with unmodified UWS. Improvement was maximal using 30 mmol/l (protein, 0 mmol/l = 0.48 +/- 0.14 and 30 mmol/l = 0.65 +/- 0.11 mg per dish; ATP, 0 mmol/l = 3.08 +/- 0.63 and 30 mmol/l = 4.32 +/- 0.90 nmol/mg protein; ADP, 0 mmol/l = 3.76 +/- 0.80 and 30 mmol/l = 4.63 +/- 0.38 nmol/mg protein, mean +/- SD). Total adenine nucleotides tended to increase at any glucose concentration (p = 0.07 by ANOVA) and were significantly better with 30 mmol/l glucose (0 mmol/l = 7.61 +/- 1.58 and 30 mmol/l = 9.62 +/- 1.08 nmol/mg protein). CONCLUSIONS: Increasing the glucose concentration from 0 to 30 mmol/l improved adenine nucleotide and cellular protein preservation in this in vitro assessment.

Adenine Nucleotides↗

PubMed1992

Alternative techniques of cardioplegia.

BACKGROUND: Although normothermic cardioplegia has been used with acceptable clinical results, no studies have previously been performed to determine the metabolic consequences of these various techniques of myocardial protection. Therefore, we have performed a randomized clinical trial to assess the effects of three cardioplegic techniques on myocardial metabolic recovery. METHODS AND RESULTS: Seventy-four patients undergoing coronary artery bypass graft surgery were randomized to receive normothermic antegrade blood cardioplegia (n = 25), normothermic retrograde blood cardioplegia (n = 23), or intermittent cold antegrade blood cardioplegia (n = 26). Myocardial oxygen consumption and lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during the operation, and cardiac creatine kinase isoenzyme (CK-MB) release was assessed after surgery. Warm antegrade cardioplegia maximized myocardial oxygen consumption during cardioplegic delivery. Postoperative CK-MB release was less after warm antegrade cardioplegia, but the difference was not statistically significant. Warm retrograde cardioplegia resulted in the greatest degree of anaerobic lactate production but did not increase morbidity and mortality. Perioperative myocardial infarctions and postoperative low-output syndrome were most common after cold cardioplegia, but this trend was not statistically significant. During warm antegrade cardioplegia, adenosine triphosphate (ATP) was metabolized to diffusible precursors, which were washed out during cardioplegic infusion. Warm retrograde cardioplegia produced a breakdown of ATP to inosine and hypoxanthine, small molecules that accumulated during the cross-clamp period and were not washed out, perhaps because of inadequate perfusion with retrograde delivery. During cold cardioplegia, ATP was dephosphorylated, and adenosine diphosphate, adenosine monophosphate, and adenosine accumulated. These compounds were not regenerated to ATP but were not washed out of myocytes because they are large anionic molecules. CONCLUSIONS: Intermittent cold cardioplegia inhibited mitochondrial function but prevented the degradation of adenine nucleotides. Warm antegrade cardioplegia had the greatest myocardial oxygen consumption, and warm retrograde cardioplegia had the greatest anaerobic lactate production. There were no differences in clinical outcomes between cardioplegic groups.

Adenosine Triphosphate↗

PubMed1992

Coronary artery bypass grafting in patients with poor ventricular function. Cardiovascular Surgeons of the University of Toronto.

Although patients with severe ventricular dysfunction have improved long-term survival times after coronary bypass procedures, operative morbidity and mortality rates remain high. This study was designed to identify the contemporary risk factors for isolated coronary artery bypass grafting in this high-risk subgroup. Between January 1982 and December 1990, a total of 12,471 patients underwent isolated coronary artery bypass grafting. The 9445 patients with preoperative ejection fractions greater than 40% had a lower operative mortality rate (2.3%) than that of the 2539 patients with ejection fractions between 20% and 40% (4.8%) and that of the 487 patients with ejection fractions less than 20% (9.8%; p less than 0.001). However, patients with ejection fractions of less than 20% were demographically distinct from those with higher ejection fractions. This group was older, with fewer women, a higher frequency of left main stenosis, and more frequent requirement of urgent operation for unstable angina. The risk factors for operative death also varied with preoperative ejection fraction. The traditionally accepted risk factors--urgency of operation, left main coronary artery stenosis, reoperation, sex, and age--were predictive of risk of operative death for patients with ejection fractions greater than 40%. The risk of operative death for patients with ejection fractions between 20% and 40% was predicted by urgency of operation, reoperation, sex, myocardial protection, and age. The only predictor of risk of operative death for patients with ejection fractions less than 20% was urgency of operation. Patients undergoing isolated coronary artery bypass grafting who have severe ventricular dysfunction are therefore a highly selected, high-risk subgroup of patients who risk depends on the urgency of operation. Strategies to improve the results in these patients should be focused on patient selection, improvement of myocardial protection, and more aggressive preoperative treatment of myocardial ischemia.

Age Factors↗

PubMed1992

The effect of warm heart surgery on postoperative bleeding.

The effects of normothermic systemic perfusion (35 degrees to 37 degrees C; n = 73) were compared with those of moderately hypothermic systemic perfusion (25 degrees to 29 degrees C; n = 73) with respect to blood loss, transfusion requirements, and platelet levels in 146 patients undergoing isolated, primary coronary artery bypass grafting. In addition, most patients were given an antifibrinolytic medication during operation as follows: tranexamic acid (10 gm intravenously; n = 63), epsilon-aminocaproic acid (15 gm intravenously; n = 63), or no drug as a control. (n = 20). Normothermic patients tended to bleed less at 24 hours (warm, 864 +/- 42 ml and cold, 918 +/- 68 ml), but these differences were not statistically significant. Patients receiving either tranexamic acid or epsilon-aminocaproic acid, regardless of perfusion temperature, bled less after 6, 12, and 24 hours than did cold control patients (p less than 0.05). Warm control patients also bled less than did cold control patients after 6 or 12 hours (p less than 0.05), and neither drug further reduced blood loss in these patients. Circulating platelet levels were better preserved in patients receiving either tranexamic acid or epsilon-aminocaproic acid and in patients with warm perfusion and no drug than in cold control patients. Normothermic systemic perfusion, tranexamic acid, and epsilon-aminocaproic acid each reduced postoperative blood loss and preserved platelets.

Aminocaproic Acid↗

PubMed1992

Effect of oxygen tension and cardiovascular operations on the myocardial antioxidant enzyme activities in patients with tetralogy of Fallot and aorta-coronary bypass.

Since the chronically cyanotic myocardium appears to be more susceptible to reperfusion injury after cardiac operations than the noncyanotic myocardium, we studied the association between the preoperative arterial oxygen tension and the myocardial superoxide dismutase, catalase, and glutathione peroxidase activities. Fourteen patients with tetralogy of Fallot scheduled for elective operations had baseline arterial blood gas measurements done before operation. During the operation right ventricular biopsy specimens were taken for enzyme analysis immediately before cold blood cardioplegic arrest and 20 minutes after crossclamp removal. The tissue antioxidant enzyme activities of the patients with tetralogy of Fallot were compared with the myocardial results in 15 adults with stable angina pectoris having elective aorta-coronary artery bypass graft operations. Myocardial tissues removed from two patients with hypertrophic obstructive cardiomyopathy who had corrective operations were analyzed for antioxidant activities. There were no changes in myocardial antioxidant enzyme activities during the operation in the patients with tetralogy of Fallot and coronary artery bypass graft. The myocardial superoxide dismutase, catalase, and glutathione peroxidase activities correlated (0.82, 0.68, and 0.89, respectively) significantly (p values were less than 0.01, 0.05, and 0.01, respectively) with the preoperative arterial oxygen tensions in the patients with tetralogy of Fallot. The myocardial glutathione peroxidase activities were at least four times higher in the myocardium of patients with coronary artery bypass graft and hypertrophic obstructive cardiomyopathy than in that of those with tetralogy of Fallot. This study provides putative evidence that the myocardium of patients with tetralogy of Fallot is a risk of oxygen-derived free radical injury during and immediately after corrective cardiovascular operations.

Catalase↗

PubMed1991

Effect of orally administered alpha-tocopheryl acetate on human myocardial alpha-tocopherol levels.

Free radical injury may contribute to the delayed postoperative recovery of myocardial metabolism and ventricular function after elective coronary artery revascularization. This clinical study was designed to evaluate, in stable angina patients having aortocoronary bypass surgery, whether orally administered alpha-tocopheryl acetate was effective in increasing myocardial alpha-tocopherol levels and the effect of cardioplegic arrest followed by reperfusion on the myocardial alpha-tocopherol levels. Twenty-four patients with stable angina pectoris for elective revascularization received preoperatively the natural stereoisomer of alpha-tocopheryl acetate labelled with deuterium (D3) and six patients were used as controls. Since four patients who received 300 mg of D3-alpha-tocopheryl acetate preoperatively for 1 and 2 days did not have significant increases in their myocardial total or D3-tocopherol levels, the remaining 20 patients received 100 mg (n = 6), 300 mg (n = 8), or 900 mg (n = 6) of D3-alpha-tocopheryl acetate for 14 consecutive preoperative days. The left ventricular deuterated and nondeuterated alpha-tocopherol levels were measured by gas chromatography/mass spectrometry. Although there was a decrease (p less than 0.05) in myocardial alpha-tocopherol levels with the onset of reperfusion (cross-clamp removal), the myocardial tocopherol levels were not statistically different from preoperative levels by 20 minutes of reperfusion. At least 300 mg of alpha-tocopherol must be taken orally for 14 consecutive days to double the myocardial alpha-tocopherol levels.

Administration, Oral↗