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Biomedical subjects

R M Engelman

Publications and source records attributed to R M Engelman.

At least 145 records · Page 8Linked to original sources

Effect of superoxide dismutase and catalase on myocardial energy metabolism during ischemia and reperfusion.

Survival of cardiac patients undergoing heart surgery depends critically upon the recovery of myocardial energy metabolism during reperfusion of ischemic myocardium. The present study compares various parameters of myocardial energy metabolism using an isolated in situ pig heart. The left anterior descending (LAD) coronary artery was occluded for 60 min, followed by 60 min of global hypothermic cardioplegic arrest and 60 min of reperfusion. Free radical scavengers [superoxide dismutase SOD and catalase] were used to protect the ischemic heart from reperfusion injury. In both control and SOD plus catalase-treated groups, ATP, creatine phosphate (CP), ATP/ADP ratio, energy charge and phosphorylation potential dropped significantly during ischemic insult. After reperfusion, CP, ATP/ADP ratio and phosphorylation potential improved significantly, but they were restored to control level only in treated animals. In either case, free energy of ATP hydrolysis (delta G) lowered only by 5% during ischemia, but recovered promptly upon reperfusion. SOD and catalase also improved coronary blood flow and reduced creatine kinase release compared to those of untreated animals, suggesting improved myocardial recovery upon reperfusion. Our results suggest that SOD and catalase significantly improve the myocardial recovery during reperfusion by enhancing rephosphorylation steps, and the value of delta G is more critical compared to those of ATP and CP for myocardial recovery.

Adenosine Triphosphate↗

Mepacrine, a phospholipase inhibitor. A potential tool for modifying myocardial reperfusion injury.

Cardioprotective effects of phospholipase inhibitor, mepacrine, on ischemic reperfused myocardium were investigated in the isolated in situ pig heart preparation, which was subjected to 120 minutes of regional ischemia, with the final 60 minutes having superimposed global cardioplegic arrest followed by 60 minutes of reperfusion. Mepacrine (0.05 mmol/L) was administered before ischemia into the perfusion circuit in 15 of 29 experiments. Significant depletion of myocardial phospholipids occurred in nontreated animals during 60 minutes of reperfusion. Mepacrine prevented the reperfusion-induced phospholipid degradation. Further, the level of high-energy phosphate compounds was higher during ischemia and reperfusion in the mepacrine-treated hearts. Left ventricular developed pressure, maximum rate of rise of left ventricular pressure, and left ventricular end-diastolic pressure were measured under isovolumic conditions to assess cardiac contractility and compliance. During incubation with mepacrine, before ischemia, left ventricular developed pressure and maximum rate of rise of left ventricular pressure decreased to 45% and 51% of baseline values, respectively. This initial decline was improved to 65% and 70% in mepacrine-treated animals during the early period of regional ischemia. In the nontreated control heart, a progressive decline in contractility was observed with ischemia such that no significant difference was apparent in the two groups. Reperfusion resulted in a further deterioration of global cardiac performance in both mepacrine-treated and control animals. Although pretreatment with mepacrine did not improve contractility, myocardial oxygen consumption, coronary flow, and cardiac compliance significantly improved. These results suggest that myocardial injury may develop during reperfusion after temporary ischemia. Mepacrine inhibits such injury by acting as a phospholipase inhibitor, but it also behaves as a negative inotropic agent in ischemic reperfused myocardium.

Animals↗

Metabolic enhancement of myocardial preservation during cardioplegic arrest.

An experimental study was undertaken to evaluate the relative efficacy of oxygenated versus unoxygenated cardioplegic solutions and to determine if the addition of certain metabolically active substrates to cardioplegic solutions had any effect on myocardial preservation. Sixty-one pigs were divided into seven groups of animals (5 to 15 animals per group). The impact of different cardioplegic vehicles, i.e., crystalloid versus the oxygen-carrying vehicles, blood and Fluosol-DA, on preservation of high-energy phosphates (adenosine triphosphate and creatine phosphate) was examined in the first three animal groups. The influence of Krebs cycle intermediates, i.e., glutamate, malate, succinate and fumarate, on adenosine triphosphate and creatine phosphate preservation was evaluated in the other four animal groups. All hearts underwent 120 minutes of hypothermic cardioplegic arrest at 15 degrees C followed by 60 minutes of normothermic reperfusion. Higher adenosine triphosphate and creatine phosphate levels were maintained during arrest when oxygenated solutions were used as the cardioplegic vehicle and when any of the four intermediates were added to the crystalloid cardioplegic solution, especially succinate and fumarate. During reperfusion, however, adenosine triphosphate levels were uniformly lower than control whereas creatine phosphate levels rose to either control levels or higher in all groups. No significant intergroup difference could be identified during reperfusion. These findings lead to the conclusion that the presence of either oxygen or certain Krebs cycle intermediates enhances the protective effect of hyperkalemic hypothermic cardioplegia on high-energy phosphates during the arrest period only. This enhancement is not maintained during the reperfusion period.

Adenosine Triphosphate↗

Cardiac performance during reperfusion improved by pretreatment with oxygen free-radical scavengers.

We studied the effects of oxygen free radicals on cardiac performance during reperfusion of ischemic myocardium. The pig heart, isolated in situ, was subjected to 60 minutes of regional ischemia at normothermia by occlusion of the left anterior descending coronary artery followed by 60 minutes of hypothermic cardioplegic arrest and 60 minutes of normothermic reperfusion. The oxygen free-radical scavengers, superoxide dismutase and catalase, were administered before occlusion of the left anterior descending coronary artery in the experimental group. The generation of free radicals in the untreated group, estimated by the measurement of malondialdehyde in the perfusate, was significant during reperfusion and was associated with a corresponding increase in creatine kinase. Superoxide dismutase and catalase significantly slowed the appearance of malondialdehyde and the release of creatine kinase during reperfusion. Superoxide dismutase and catalase did not alter coronary flow and myocardial oxygen extraction or consumption during occlusion of the left anterior descending coronary artery; however, coronary flow and oxygen consumption were significantly higher (p less than 0.05) during reperfusion in hearts treated with antioxidants. Left ventricular developed pressure and its maximum first derivative were measured under isovolumic conditions. In the untreated group, left ventricular developed pressure and its maximum first derivative declined to 61.1% and 57.1% of baseline values, respectively, after 60 minutes' occlusion of the left anterior descending, and to 45% of baseline values after 15 minutes of reperfusion. The decline in left ventricular developed pressure and its maximum first derivative during reperfusion was significantly (p less than 0.05) inhibited by superoxide dismutase and catalase, but left ventricular end-diastolic pressure was not significantly altered. These results implicate oxygen-derived free radicals in the injury resulting from reperfusion of ischemic myocardium and suggest that oxygen free-radical scavengers effectively protect against such injury.

Animals↗

Late postoperative tamponade following coronary artery bypass grafting in patients on antiplatelet therapy.

Myocardial revascularization was performed in 1,361 patients over a 66-month period (February, 1978 to August, 1983) without a single occurrence of late cardiac tamponade. During a subsequent 4-month-period, aspirin and dipyridamole were administered routinely to all coronary bypass patients. The incidence of late cardiac tamponade rose significantly (p less than 0.001) to 3 of 85 patients (3.5%). Routine perioperative administration of aspirin and dipyridamole to patients undergoing myocardial revascularization may be associated with an increased incidence of delayed cardiac tamponade.

Adult↗

Phrenic nerve paresis associated with the use of iced slush and the cooling jacket for topical hypothermia.

Phrenic nerve injury has been reported with the use of iced slush for topical cardiac hypothermia. To study this problem in both valve and coronary procedures, we tried to detect phrenic nerve injury in five groups of patients undergoing cardiac operations in which different techniques of topical hypothermia were used. The results indicate a 24% incidence of left phrenic nerve paresis in patients undergoing coronary bypass with iced slush used for topical hypothermia, 12.5% in patients in whom the cardiac cooling jacket was used in association with cold saline, and 22.9% in patients in whom both the cardiac cooling jacket and iced slush were used in the pericardial sac. There was no phrenic nerve injury when saline alone was used. Phrenic paresis is transient and of no clinical significance except when bilateral. Avoidance of contact of either the cooling jacket or iced slush with the phrenic nerve could avoid this complication.

Cold Temperature↗

Does the type of venous drainage or cardioplegia affect postoperative conduction and atrial arrhythmias?

Five consecutive patient groups undergoing coronary bypass surgery were studied for postoperative conduction disturbances and atrial arrhythmias. Group I (50 patients) had blood cardioplegic solution (25 meq/liter potassium) and unsnared venae cavae, group II (156 patients) had low-volume crystalloid cardioplegic solution (25 meq/liter potassium) and unsnared venae cavae, group III (56 patients) was similar to group II except that a single cavoatrial venous cannula was used instead of two separate cannulas, group IV (218 patients) had high-volume crystalloid cardioplegic solution (25 meq/liter potassium) and snared venae cavae, and group V (37 patients) was the same as group IV except that the cardioplegic solution contained 10 meq/liter potassium after the first dose, which contained 25 meq/liter. All postoperative electrocardiograms were analyzed for conduction disturbances and atrial arrhythmias. The results showed a significantly lower incidence of conduction disturbances in group I (12%) as compared with groups II to IV. In addition, groups IV and V (high-volume crystalloid cardioplegic solution) had a significantly higher incidence of conduction disturbances than groups II and III (lower-volume crystalloid solution) (55.0% and 62.1% vs 26.2% and 35.1%, respectively). The majority of these disturbances were temporary. Group I also had the lowest incidence of postoperative atrial arrhythmias (3.8%). There was no significant difference between the groups receiving high- and low-volume crystalloid solution. It is concluded that blood cardioplegic solution affords the best protection against postoperative conduction disturbances and atrial arrhythmias. High-volume crystalloid cardioplegic solution affords the least protection against conduction disturbances but has no effect on atrial arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

Postinfarction angina: an expanding subset of patients undergoing coronary artery bypass.

An analysis of patients undergoing coronary artery bypass for unstable postinfarction angina (less than or equal to 30 days of infarct) during two time periods was undertaken: Group I, January, 1982, through December, 1982; Group II, September, 1983, through August, 1984. Clinical, angiographic, and operative data were coded, and statistical analysis was used to compare the two patient groups, evaluate operative results, and identify risk factors. The incidence of unstable postinfarction angina as an indication for bypass grafting increased significantly (p less than 0.01) from the first to the second time frame, 8.7% (24/276) to 18% (51/283). A greater proportion of Group II patients were operated upon within 7 days of infarct (37% versus 21%, p less than 0.01). All other variables examined were similar in the two patient groups. Analysis of the combined Group I and II patients (N = 75) indicates the following: The ratio of transmural to nontransmural infarction was 39%/61%, and 39% of patients had a previous infarction. Three-vessel disease was present in 76%, two-vessel in 21%, one-vessel in 3%, and left main disease in 20%. Left ventricular ejection fraction was greater than or equal to 40% in 27% of patients, less than 40% in 32%, and not obtained in 41%. Mean left ventricular end-diastolic pressure was 19.5 mm Hg. Intra-aortic balloon pumping was necessary preoperatively in 39%. The mean interval from infarction to revascularization was 12 days, and the mean number of grafts was 3.1 (range one to six). The overall in-hospital mortality was 8% (6/75). Statistical analysis demonstrated that decreased ejection fraction was associated with an increased risk of mortality. No other variables were correlated with mortality. Mean follow-up for the combined Group I and II patients is 13 months (range 4 to 32). Ninety percent of survivors remain in Canadian Heart Association Functional Class I and 6% in Class II. No late deaths have occurred. Patients with unstable postinfarction angina constitute an ever-increasing subset of the coronary bypass population of the 1980s. Operation can be performed with a satisfactory mortality and excellent long-term outlook compared to less acceptable published results with medical management alone. Preoperative left ventricular function constitutes the major indicator of operative risk.

Angina Pectoris↗

A comparison of Cell Saver versus ultrafilter during coronary artery bypass operations.

A study was performed to evaluate two blood conservation techniques that can be used with high-volume crystalloid cardioplegia. Twenty-seven patients undergoing coronary artery bypass with high-volume crystalloid cardioplegia were randomized into two groups: In 12 Group I patients the coronary sinus effluent was drained into a Cell Saver and the recovered, washed red cells were then reinfused. In 15 Group II patients the coronary sinus effluent was absorbed systemically and excess volume was removed from the cardiopulmonary bypass circuit by an ultrafilter. These two groups were compared with a retrospective control group in which the cardioplegic solution had been evacuated from the right atrium and discarded. Both the techniques resulted in significant and equivalent red blood cell conservation compared with the retrospective control group. The ultrafilter was associated with less derangement of prothrombin time. More complete potassium removal was provided by the Cell Saver.

Blood↗

Short term survival following perfusion with fluosol-DA for cardiopulmonary bypass.

Seven dogs were perfused on cardiopulmonary bypass for one hour using a perfusate which included one liter of Fluosol in order to investigate tissue oxygenation during perfusion as well as possible biochemical and histopathologic effects of Fluosol on various organs. Tissue oxygenation during cardiopulmonary bypass was evaluated by measuring arterial and venous oxygen tensions as well as oxygen content and arterial pH. Biochemical studies were measured pre and post bypass and were followed up to 48 hours following discontinuation of cardiopulmonary bypass. The animals were observed clinically for evidence of abnormal behavior during 30 days of follow-up and were then sacrificed. Biopsies from the heart, lung, liver, spleen, kidney and brain were examined by light and electron microscopy. Excellent tissue oxygenation and normal acid base status was seen uniformly during cardiopulmonary bypass. Clinical status and biochemical parameters remained normal during followup. Histopathologic examination revealed only a marked increase in phagocytic histiocytes in the reticuloendothelial system of liver and spleen with sinusoidal compression but no functional impairment.

Animals↗

Rebound vasospasm after coronary revascularization in association with calcium antagonist withdrawal.

Four patients experienced life-threatening coronary vasospasm following discontinuation of calcium channel blocking medication at the time of coronary revascularization. The last dose of the calcium blocker in each instance was administered between 8 and 18 hours before operation. Two of the patients were receiving diltiazem (60 mg four times a day) and 2, nifedipine (20 mg four times a day). During this same period, 16 patients had received diltiazem (12.5% incidence of vasospasm) and more than 100 patients, nifedipine (less than 2% incidence). In 3 of the 4 patients, coronary spasm was identified by electrocardiogram and documented as the cause of ischemia in the distribution of a nondiseased right coronary artery. In the fourth patient, spasm had occurred in the distribution of a bypassed left anterior descending coronary artery. In 2 patients in whom the problem was recognized retrospectively, an infarct developed; 1 patient died. In the 2 patients in whom the problem was apparent prior to infarction, nitroglycerin (1 to 3 micrograms/kg/min, intravenously) and nifedipine (10 mg, sublingually every 4 to 6 hours) successfully reversed the ischemic process. The routine administration of calcium at the completion of coronary revascularization may be ill-advised in patients in whom calcium channel blockers have been utilized. Postoperative therapy of this condition with intravenous administration of nitroglycerin and sublingual administration of nifedipine seems to be effective when instituted early.

Adult↗

Traumatic ventricular septal defect following closed-chest massage: a new approach to closure.

A 59-year-old man underwent a quadruple coronary bypass. Nine hours postoperatively, cardiac arrest developed; it was preceded by bradycardia resistant to pacing. Closed-chest massage resulted in a rapid recovery of stable cardiac function followed by the development of cardiogenic shock. A new systolic murmur was appreciated 36 hours following arrest. It was diagnosed at catheterization as a ventricular septal defect that was subsequently found to lie in the posterior ventricular septum, and two operations were necessary to effect closure. The final operation was performed with exposure of the septal defect through the right atrium. Sixteen months after operation, the patient remained well. To our knowledge, this is the first reported instance of a ventricular septal defect occurring secondary to closed-chest massage and also of the closure of a traumatic defect using a right atrial approach.

Female↗

Experimental evaluation of secondary blood cardioplegia.

Reperfusion damage after ischemia may be evidenced by myocardial cell edema, intracellular calcium accumulation, and limited utilization of oxygen. The need for cardioplegic arrest during initial reperfusion to allow oxygen to be used for reversing ischemic damage rather than for electromechanical activity has been propounded by some researchers. Reports of greater postischemic compliance and performance, low postischemic edema, and greater oxygen uptake at a perfusion pressure of 50 mm Hg or lower have been cited. The present study was conducted on 24 pigs having 2-hr cardioplegic arrest, which of 12 underwent normal reperfusion and 12 experienced secondary cardioplegia followed by normal reperfusion. The results showed that in spite of improved high-energy phosphate preservation, the secondary cardioplegia group had higher myocardial edema, less coronary flow, and poorer contractility and compliance at the end of 1 hr of reperfusion. Because of these findings and contradictory results reported by other groups, caution is urged in the clinical extrapolation of the results of such studies pending further investigations.

Animals↗

High-volume crystalloid cardioplegia. An improved method of myocardial preservation.

Controlled metabolic studies were used to gauge the relative efficacy of three cardioplegic techniques in 41 patients undergoing multiple coronary artery bypass grafts. Normal-volume (1,946 +/- 155 ml) crystalloid cardioplegia (NVCC) (14 patients) was compared to high-volume (4,961 +/- 282 ml) crystalloid cardioplegia (HVCC) (14 patients) and to blood cardioplegia (BC) (1,672 +/- 127 ml) (13 patients). Measurements of coronary blood flow, coronary vascular resistance, coronary arteriovenous oxygen difference, myocardial oxygen consumption and extraction, and myocardial lactate and potassium extraction and release were all measured in the isolated, vented, paced, beating heart, before and for 20 minutes after a 1 hour arrest interval during which revascularization was completed. Additionally, during administration of the cardioplegic solution, infusion flow rate, myocardial oxygen consumption and extraction, and lactate and potassium release and uptake were noted. The results indicate that during cardioplegic administration, myocardial oxygen consumption is 1 ml O2/min with crystalloid infusion and 2.6 ml O2/min during BC infusion. The volume of crystalloid solution administered contributed to increased oxygen utilization during HVCC compared to NVCC, whereas BC promoted the highest oxygen utilization of the three groups. Potassium absorption was nearly three times greater during BC than during crystalloid administration. During myocardial reperfusion, oxygen extraction was maintained at prearrest levels only in the HVCC group. Following both NVCC and BC, oxygen extraction was depressed during the first 5 minutes of reperfusion, and the difference between the latter two groups and HVCC was significant (p less than 0.01). The rapid recovery in normal metabolic function seen with HVCC allows early discontinuation of cardiopulmonary bypass without myocardial metabolic depression.

Adult↗

Mechanism of plasma catecholamine increases during coronary artery bypass and valve procedures.

Nineteen patients undergoing coronary revascularization (14 patients) or valve replacement (five patients) were studied to monitor the catecholamine levels following operation and for each of three consecutive postoperative days. A significant (p less than 0.01) elevation was observed in both the serum norepinephrine and epinephrine levels immediately following operation, with both responding in a similar fashion (r = 0.804, p = 0.016). While epinephrine returned to control levels within 3 days of operation, the norepinephrine levels remained above control. The elevation in catecholamines associated with cardiac operation is presumed to be secondary to (1) the stress of surgical trauma and (2) the influence of cardiopulmonary bypass, with its attendant hypothermia and hemodynamic alterations. A comparative analysis was performed of (1) the type of operation, (2) the sex of the patient, (3) the presence of postoperative arrhythmia, (4) the history of receiving propranolol, (5) the duration of cardiopulmonary bypass, (6) the duration of operation, and (7) the volume of fluid gradient absorbed during operation. None of these parameters except the sex of the patient was significantly related to the change in either norepinephrine or epinephrine associated with the operation. There was a significantly (p less than 0.05) higher epinephrine level at day 2 and 3 following operation in women than in men. None of the 19 patients had postoperative complications except for arrhythmias, which developed in nine patients and were not associated with the catecholamine responses. It is concluded that peak catecholamine stimulation does not reflect the ease of postoperative recovery. The duration of bypass and operation were also not directly related to the level of stimulation. It is apparent that there are multiple factors which combine to influence catecholamine secretion during cardiopulmonary bypass.

Adult↗