TITLE: Time course of lysophosphatidylcholine release from ischemic human myocardium parallels the time course of early ischemic ventricular arrhythmia

JOURNAL: Coronary Artery Disease
PAGES: 0019-0027

AUTHOR: Steven P. Sedlis, Mae Hom, Jeffrey M. Sequeira, Marc Tritel, Aaron Gindea, Jack H. Ladenson, Allan S. Jaffe, Rick Esposito

ADDRESS: Division of Cardiology and Cardiovascular Surgery at the New York Department of Veterans Affairs Medical Center and New York University School of Medicine, New York, USA. Department of Biology, St Joseph's College, Brooklyn, New York, USA. Department of Cardiovascular Division, SUNY Health Sciences Center, Syracuse, USA. Department of Laboratory Medicine, Division of Washington University School of Medicine, St Louis, Missouri, USA

ABSTRACT: Background We determined the kinetics of the release of lysophosphatidylcholine (LPC) into the coronary sinus of patients undergoing stress tests after coronary artery bypass grafting. The kinetics were consistent with a role for this amphiphile in the pathogenesis of ischemic ventricular arrhythmia, a major cause of sudden death.Methods Stress testing was initiated in the operating suite by pacing at a rate of 160 beats/min for 2 min. Ischemia was then induced byclamping the bypass grafts to the anterior wall for a maximal time of 4 min.Results The pacing procedure induced a prompt but reversible increase in coronary sinus LPC concentration from a baseline of 60.9 ± 2.5 to 83.8 ± 5.0 μmol/l via pacing alone, and a further increase to 101.8 ± 6.7 mmol/l when the grafts were clamped for 2 min (P < 0.01). Six minutes after the cessation of pacing, LPC concentration returned to 67.5 ± 4.4 μ:mol/l.Conclusions These results demonstrate that severe myocardial ischemia is an agonist for rapid release of LPC from the myocardium. Kinetics of this release paralleled the time-course of early onset of electrophysiologic changes in isolated myocytes and perfused heart preparations invitro. These results indicate that LPC may have an important role in the pathogenesis of ischemic ventricular arrhythmia in patients.

KEYWORDS: myocardial ischemia lysophosphatidylcholine ventricular arrythmia coronary