Lysophosphoglycerides in ischemic myocardium effluents and potentiation of their arrhythmogenic effects

Abstract

Lysophosphoglycerides accumulate in ischemic myocardium. To determine whether lysophosphatidylcholine (LPC) concentrations increase in extracellular fluid and may be arrhythmogenic, the anterior descending coronary artery of the open-chest cat (n = 12) was perfused with a Krebs-albumin solution after 10 min of ischemia and the effluent assayed for LPC. A 2-fold increase in LPC (0.097 .+-. 0.02 to 0.170 .+-. 0.03 mM) was observed. Microelectrode intracellular recordings from normal feline endocardium at pH 7.4 in vitro revealed little change in action potentials when superfused with feline plasma despite augmented LPC to twice normal levels (0.74 mM). At pH 6.7, marked changes were elicted by LPC-enriched plasma including diminished resting membrane potential (-96 .+-. 1 to -35 .+-. 7 mV), amplitude (102 .+-. 3 to 36 .+-. 8 mV), maximum rate of rise (.ovrhdot.Vmax) of phase 0 (178 .+-. 24 to 26 .+-. 11 V/s) and conduction velocity with fractionation of the action potential. Acidified control plasma decreased only .ovrhdot.Vmax (from 161 to 57 V/s). LPC increases 2-fold in effluents from cat myocardium in vivo after 10 min of ischemia and, coupled with ischemia-induced acidosis, is sufficient to induce marked electrophysiological derangements in vitro.