Arrhythmogenic properties of phospholipid metabolites associated with myocardial ischemia

Several observations suggest that the accumulation of metabolites within ischemic regions may contribute to the electrophysiological derangements characteristic of ischemic myocardium. We, and more recently others, have detected an increase in lysophosphoglycerides (LPGs) in ischemic tissue in vivo as well as in effluents from ischemic regions. At comparable concentrations, LPGs induce electrophysiological alterations in vitro analogous to changes seen in vivo with ischemia. Experiments with [14C]lysophosphatidylcholine indicated that incorporation comprising less than 1% of total cellular phospholipid is sufficient to induce electrophysiological derangements in isolated ventricular muscle. Reduction of pH to 6.7, analogous to the fall seen within minutes in ischemic tissue in vivo, potentiates the electrophysiological actions markedly without increasing membrane incorporation. In recent studies the activity of enzymes potentially responsible for the accumulation of LPGs during ischemia has been found to be altered by concomitants of ischemia, including increased concentrations of H+ and long-chain acyl carnitine. Thus, accumulation of LPGs and related compounds may contribute substantially to induction of electrophysiological derangements accompanying ischemia and may be amenable to therapeutic manipulation designed to alleviate malignant ventricular dysrhythmia.