title: Effect of reversible ischemia on the activity of the mitochondrial ATPase: relationship to ischemic preconditioning.
abstract: The mitochondrial ATPase enzyme accounts for roughly 35-50% of the overall energy demand that leads to ATP depletion under conditions of severe myocardial ischemia. In larger mammalian hearts, this energy squandering action of the ATPase is modulated by an endogenous inhibitor protein. The present studies were undertaken to characterize the time course of inhibition of the mitochondrial ATPase in canine myocardium under conditions of severe regional ischemia in vivo. In addition, we determined if the energy sparing effects of ischemic preconditioning (PC) can be explained by persistent inhibition of the mitochondrial ATPase enzyme. The circumflex coronary artery was ligated for 1.5 min (n = 4), 5 min (n = 6), or 15 min (n = 5). In a separate group (n = 7), hearts were preconditioned by four 5-min periods of ischemia each followed by 5 min of reperfusion. Sub-mitochondrial particles were prepared from the sub-endocardial zone of the ischemic and non-ischemic regions and were assayed for oligomycin-sensitive ATPase activity. ATPase activity was reduced to about 79% at 1.5 min and to approximately 55% at 5 and 15 min of ischemia, relative to non-ischemic tissue from the same heart. The rate of HEP utilization slowed concurrently with the development of ATPase inhibition. In preconditioned myocardium, ATPase activity was not significantly different from control myocardium from the same heart. We conclude that the early inhibition of the mitochondrial ATPase activity slows the utilization of high energy phosphate and thereby serves as an important endogenous cardioprotective mechanism. Nevertheless, altered activity of the ATPase is not the explanation of the energy sparing effect of ischemic preconditioning.
authors: Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors: R S
authors: RS
authors: Vander Heide
authors: M L
authors: ML
authors: Hill
authors: K A
authors: KA
authors: Reimer
authors: R B
authors: RB
authors: Jennings
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002458:Cell Fractionation; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D004734:Energy Metabolism; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008929:Mitochondria, Heart / Q000201:enzymology* / Q000648:ultrastructure; D017202:Myocardial Ischemia / Q000201:enzymology*; D009206:Myocardium / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D010725:Phosphocreatine / Q000378:metabolism; D012016:Reference Values; D012039:Regional Blood Flow; D013367:Submitochondrial Particles / Q000201:enzymology* / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D009840:Oligomycins; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases