Biochemical Mechanisms Contributing to Ischemic Membrane Dysfuncton

Abstract

Myocardial ischemia results in multiple biochemical abnormalities, including alterations in intracellular hydrogen ion concentration, glycolytic flux, beta-oxidation, and is accompanied by the accumulation of several amphiphilic compounds including lysophospholipids (1–3) and long-chain acyl carnitines (4). Many experimental observations have demonstrated that amphiphilic compounds are modulators of membrane-bound enzymic activities (5,6), ligand-receptor coupling (7) and that they alter the kinetics of transmembrane ion channels (8,9). Incorporation of small amounts of lysophosphatidylcholine (LPC) into canine Purkinje fibers results in profound electrophysiologic alterations even when only 1–2% of sarcolemmal phospholipids are constituted by LPC (10). Taken together, a large body of evidence suggests that amphiphiles may be one biochemical mediator of membrane dysfunction during myocardial ischemia.