Role of anaerobic metabolism in the preservation of functional capacity and structure of anoxic myocardium

Abstract

A B ST R A CT Employing an isolated perfused rat heart preparation, we investigated the contriblution of anaerobic metabolic energy to the lerformance, recoverability, and ultrastructure of the heart perfused at 320C in 5% albumin in Krebs-Ringer Bicarbonate solution. During exposure to anoxia for 30 min, inclusion in the perfusate of the anaerobic substrate, glucose, resulted in marked improvement in electrical and mechanical performance of the heart and in enhanced recovery during the subsequent period of reoxygeiiation. Lactate production was fivefold greater in the glucose-supported anoxic heart than in the anoxic heart without glucose. Electron microscope sections of the hearts exposed to anoxia in the absence of glucose anaerobically derived metabolic energy to the electrical and mechanical performance of the heart, to functional recoverability after exposure to anoxia, or to the prevention of intracellular structural alterations accompanying anoxic exposure.Induction of myocardial hypoxia by simple cessation of coronary perfusion, in vivo or in vitro, does not permit a steady supply of anaerobic substrate to the myocardium. Furthermore, the effects of accumulated end products of anaerobic metabolism are not controlled under these circumstances. Studies with perfused myocardial strips, which avoid these difficulties, do not yield information on spontaneous electrical activity or on electromechanical integration of cardiac function. With these considerations in mind the present studies on the effects of anoxia on the isolated perfused rat heart were initiated. This preparation permits study of electrical and mechanical performance of the isolated heart during relatively prolonged experiments and instantaneous addition or deletion of anaerobic substrate while perfusion is maintained at a constant rate. The studies were designed to determine the degree to which the presence of the anaerobic substrate, glucose, affects the performance, recoverability, and ultrastructure of the perfused anoxic heart. METHODSThe hearts used in these studies were removed from male albino (Wistar) rats, weighing from 180 to 235 g. The rats were fed ad lib. with standard Purina laboratory chow until they were sacrificed. The animals were decapitated, the chest opened within 30 sec with a subxiphoid incision, and the heart flooded immediately with ice-cold Ringer's solution. This maneuver produced rapidThe Journal of Clinical Investigation Volume 47 1968 403 cessation of the heart beat, after which the heart was dissected from the mediastinum with an attached aortic stump 5 mm long. The heart was then mounted on the perfusion cannula which consisted of a No. 17 TW needle with a rounded and smoothed end and notched 3 mm above the tip. The tip of the cannula was placed in the aortic root which was attached firmly via a silk 3-0 ligature applied to the notch in the cannula. The time from extirpation of the heart to in vitro perfusion was 3-5 min.The perfusion system, as illustrated in Fig. 1, was recirculating in type and consisted o...

Effect of free fatty acids on myocardial function and metabolism in the ischemic dog heart

“…Although conflicting results have been obtained in assessing the efficacy of glucose in the treatment of acute coronary ischemia (34)(35)(36), evidence has been provided of prolonged survival of ischemic tissue during glucose treatment (37)(38)(39). The rationale suggested for using glucose or combinations of glucose, K, and insulin in treating myocardial infarction has been to supply adequate glucose to the heart, thereby obtaining energy from anaerobic breakdown of glucose (37,38,40), reverse potassium loss from the heart, and maintain membrane stability (41,42).…”

Deletion of thioredoxin-interacting protein in mice impairs mitochondrial function but protects the myocardium from ischemia-reperfusion injury

“…Because lipids are not used as major precursors for anaerobic metabolism, glucose is the primary substrate to support anaerobic metabolism. Thus, anaerobic metabolism with concomitant increased use of glucose, as fostered by Txnip deletion, plays a significant role in preserving myocardial function and structure and in promoting recoverability of the hypoxic heart (35).…”

“…A previous report demonstrated that inclusion of glucose in the perfusate of isolated perfused rat heart preparations results in marked improvement in electrical and mechanical performance of the heart subjected to anoxia and in enhanced recovery during the subsequent period of reoxygenation (35). While lactate production was 5-fold greater in the glucosesupported anoxic heart than in the anoxic heart without glucose, morphologic changes of mitochondria during anoxia were averted by inclusion of glucose in the perfusion fluid (35). Thus, anaerobic metabolism, with concomitant increased use of glucose, can preserve myocardial function and structure and promote ischemic heart recovery.…”

Effects of low and high glucose in a glucose-insulin-potassium infusion on hemodynamics and exercise tolerance in patients with angina pectoris.

“…[1][2][3][4][5][6][7] However, infusion of GIK after acute myocardial infarction has been reported to have variable effects in man, producing either beneficial,8-18 deleterious or no effects'9 26 on mortality. Similarly, GIK infusions have produced variable effects on pacing-and exercise-induced angina.…”