TIME-COURSE OF LYSOPHOSPHATIDYLCHOLINE RELEASE FROM ISCHEMIC HUMAN MYOCARDIUM PARALLELS THE TIME-COURSE OF EARLY ISCHEMIC VENTRICULAR ARRHYTHMIA

Background We determined the kinetics of the release of lysophosphatid ylcholine (LPC) into the coronary sinus of patients undergoing stress tests after coronary artery bypass grafting, The kinetics were consist ent with a role for this amphiphile in the pathogenesis of ischemic ve ntricular arrhythmia, a major cause of sudden death, Methods Stress te sting was initiated in the operating suite by pacing at a rate of 160 beats/min for 2 min, Ischemia was then induced by clamping the bypass grafts to the anterior wall for a maximal time of 4 min, Results The p acing procedure induced a prompt but reversible increase in coronary s inus LPC concentration from a baseline of 60.9 +/- 2.5 to 83.8 +/- 5.0 mu mol/l via pacing alone, and a further increase to 101.8 +/- 6.7 mu mol/l when the grafts were clamped for 2 min (P< 0.01), Six minutes a fter the cessation of pacing, LPC concentration returned to 67.5 +/- 4 .4 mu mol/l, Conclusions These results demonstrate that severe myocard ial ischemia is an agonist for rapid release of LPC from the myocardiu m. Kinetics of this release paralleled the time-course of early onset of electrophysiologic changes in isolated myocytes and perfused heart preparations in vitro, These results indicate that LPC may have an imp ortant role in the pathogenesis of ischemic ventricular arrhythmia in patients.