Potential arrhythmogenic electrophysiological derangements in canine Purkinje fibers induced by lysophosphoglycerides.
We have recently detected accumulation of lysophosphoglycerides, catabolites of phospholipids, in ischemic myocardium early after coronary occlusion. In the present study we delineated effects of selected concentrations of albumin-bound lysophosphatidyl choline (LPC) comparable to those accompanying ischemia in vivo on action potentials of isolated canine Purkinje fibers. Lysophosphoglycerides induced concentration-dependent (0.75-3.0 mM) decreases in resting membrane potential, overshoot of phase 0, maximal velocity of upstroke (Vmax) of phase 0, and action potential duration. The highest concentrations (2.0-3.0 mM) induced fractionation of the action potential into several components, unresponsiveness to external stimulation, and enhanced automaticity at normal and reduced membrane potentials. LPC induced a rightward shift in the membrane response curve, a 40-fold prolongation of conduction time, and an increase in the ratio of effective refractory period to action potential duration such that the effective refractory period persisted beyond action potential duration, resulting in postrepolarization refractoriness. These electrophysiological alterations were entirely reversible after 70 minutes of perfusion without LPC, with the exception of a persistent depression in the Vmax of phase 0. Lysophosphatidyl ethanolamine (LPE) elicited alterations in action potentials indentical to those elicited by LPC. Furthermore, LPC (3.0 mM) induced comparable alterations in action potentials recorded from isolated rabbit papillary muscles. Since lysophospholipids accumulate early after myocardial ischemia, and since concentrations equivalent to those occurring in vivo induce electrophysiological alterations resembling those seen in ischemic myocardium in vivo, lysophosphoglycerides may be of major importance as biochemical mediators of malignant dysrhythmia induced by ischemia.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D003201:Computers; D003971:Diastole; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D010169:Palmitic Acids / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D011485:Protein Binding; D011690:Purkinje Fibers / Q000187:drug effects*; D012709:Serum Albumin
D008244:Lysophosphatidylcholines; D010169:Palmitic Acids; D010714:Phosphatidylethanolamines; D012709:Serum Albumin