Electrophysiological effects of amphiphiles on canine purkinje fibers. Implications for dysrhythmia secondary to ischemia.

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Abstract
Lysophosphoglycerides and long-chain acyl carnitines accumulate in ischemic myocardium soon after coronary occlusion. Since both are amphiphiles and have some structural similarities, their electrophysiological effects on transmembrane action protentials (AP) of isolated canine Purkinje fibers were studied. Lysophosphatidyl choline (LPC) in the absence of albumin induced concentration-dependent (75-300 .mu.M) and reversible decreases in maximum diastolic potential (MDP), AP amplitude, maximum upstroke velocity of phase 0 (.ovrhdot.Vmax) and action potential duration (APD). These responses were identical to those elicited by LPC in the presence of albumin at 10-fold higher concentrations (750-3000 .mu.M). Palmitoyl carnitine induced similar concentration-dependent (75-300 .mu.M) decreases in MDP, .ovrhdot.Vmax, AP amplitude and APD. At concentrations > 100 .mu.M, both compounds induced additional alterations characteristic of ischemic tissue in vivo: triangularization of the AP configuration, increased threshold for extracellular stimulation, conduction delay, non-uniform phase 0 depolarization and electrical alternans. Neither FFA [free fatty acids], glycerophosphoryl choline nor carnitine, all possible catabolites of LPC or acyl carnitine, induced any significant electrophysiological alterations analogous to those caused by LPC. The derangements induced by LPC and palmitoyl carnitine were additive. Acidosis comparable to that seen during early ischemia in vivo (pH = 6.7) led to a 2- to 3-fold leftward shift in the concentration-response curve for LPC and palmitoyl carnitine. Acidosis alone without the amphiphile during the 10-min superfusion period failed to alter MDP or AP amplitude, although .ovrhdot.Vmax was reduced (517 to 429 V/s) and APD was prolonged rather than shortened. Both lysophosphoglycerides and long-chain acyl carnitines increase in ischemic tissue and induce profound electrophysiological derangements closely analogous to those seen in ischemic myocardium in vivo, implicating both metabolites as potential progenitors of dysrhythmias during ischemia.