ATP Metabolism and Ischemic Preconditioning

Abstract

Two general facets of myocardial ischemia are the progressive loss of high energy phosphates and adenine nucleotides and the progressive accumulation of a variety of catabolites. The relative importance of ATP depletion vs. accumulation of potentially deleterious catabolites in the transition from reversible to irreversible (lethal) ischemic cell injury is uncertain. Interventions which delay the onset of lethal injury delay both facets of ischemic metabolism. Ischemic preconditioning (IP) induces tolerance to a subsequent lethal episode of myocardial ischemia which is manifest by a substantial limitation of myocardial infarct size. A key feature and the likely final pathway of ischemic preconditioning is a reduction in ischemic myocardial energy demand. This reduction in energy demand is manifest by a reduced rate of high energy phosphate utilization and reduced accumulation of products of anaerobic glycolysis. Studies to date have shown that the slower ischemic energy utilization of preconditioned myocardium is not due to earlier inhibition of the mitochondrial ATPase, nor is it a feature of post-ischemic contractile dysfunction (stunning) that normally accompanies IP. Other proposed mechanisms include catecholamine-mediated effects, activation of adenosine A1 receptors, and earlier or more complete opening of ATP-sensitive potassium (K +ATP ) channels. Which of these (or other) pathways mediate the energy sparing effects of ischemic preconditioning remains unknown.KeywordsIschemic PreconditionAdenine NucleotideAnaerobic GlycolysisHigh Energy PhosphateMitochondrial ATPaseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.