Pathophysiological concentrations of lysophosphatides and the slow response

Abstract

The concentrations of lysophosphoglycerides (LPG) in normal and ischemic (10 min) regions of feline hearts were determined in vivo under conditions employing nonacidified extraction media (chloroform:methanol) to avoid acid-induced conversion of plasmalogens to LPG. It was also perfomed to determine whether the concentrations found in ischemic myocardium elicited specific electrophysiological effects in canine Purkinje fibers in vitro compatible with depolarization dependent exclusively on the slow inward current (Isi). LPG [lysophosphatidylcholine (LPC) plus lysophosphatidylethanolamine (LPE)] increased 53% in ischemic compared with control myocardium in vivo [LPC 2.8 .+-. 0.2 (SE) to 4.5 .+-. 0.4 nmol/mg protein, P < 0.001; LPE 2.1 .+-. 0.1 to 3.0 .+-. 0.6, P < 0.05; and LPC + LPE 4.9 .+-. 0.27 to 7.5 .+-. 0.33, P < 0.001] with no significant change in diacyl phospholipids. Superfusion of Purkinje fibers at pH 7.4 with concentrations of LPC (200 .mu.M) selected based on those found in ischemic myocardium decreased maximum diastolic potential from -92 .+-. 5 (SE) to -57 .+-. 3, maximum rate of rise from 660 .+-. 47 to 11 .+-. 1 V/s, and amplitude from 132 .+-. 2 to 34 .+-. 4 mV and shortened action potential duration significantly (P < 0.01) Action potentials were abolished by either Mn2+ (5 mM) or verapamil (1 mg/l) but were unaffected by tetrodotoxin. At pH 6.6, LPC (100 .mu.M) produced similar effects and action potentials were abolished by Mn2+. Thus LPG at concentrations equivalent to those in ischemic myocardium induced electrophysiological derangements in vitro resembling those typical of ischemic tissue in vivo. The alterations observed are compatible with the appearance of potentials dependent exclusively on Isi, suggesting that the Isi may be an important contributor to the genesis of malignant dysrhythmias associated with ischemia.