The effects of lysophosphatidylcholine, a toxic metabolite of ischemia, on the components of cardiac excitability in sheep Purkinje fibers.

Abstract

Lysophosphatidylcholine (LPC) accumulates in ischemic but not normal myocardium and has electrophysiological actions. The effects of LPC on passive and active membrane properties and on repolarization in the Purkinje fibers of sheep were studied using multiple microelectrodes: one for intracellular current injection and the other for transmembrane voltage (Vm) recording. Synthetic 1-palmitoyl LPC (10-50 .mu.M) was used in normal Tyrode''s solution. These concentrations are presumably equivalent to those of free LPC in ischemic myocardium. At a low [LPC]o of 10-20 .mu.M, cable analysis showed increased membrane (Rm) and longitudinal (Ri) resistances (P < 0.010 and < 0.013, respectively); LPC increased the length (.lambda.m) and time (.tau.m) constants (P < 0.018 and < 0.010, respectively) with the balance between Rm and Ri determining input resistance. The increased Rm, without a change in threshold or resting Vm, enhanced excitability as manifested by a decrease in rheobasic current (P < 0.009) or charge threshold (P < 0.005) or a downward shift in the nonnormalized strength-duration (SDC) (P < 0.048) and charge-duration curves (CDC). Normalized SDC and CDC suggested that altered passive properties were primarily responsible for the phase of increased excitability. [LPC]o at 10-20 .mu.M decreased the maximal rate of rise of phase 0 (.ovrhdot.Vmax) (P < 0.001) even during the phase of increased excitability and depressed and flattened the .ovrhdot.Vmax vs. charge relationships. This depression of the Na system resulted in a phase of decreased excitability and often inexcitability despite Rm being maintained near or above the values observed during the control period or the phase of increased excitability. Abnormalities of repolarization included a marked increase or decrease in action potential duration, 2 stable steady states at resting and plateau Vm or 1 steady state at a low Vm. Abnormal sustained rhythmic activity was observed commonly both at high and low Vm. High [LPC]o of over 40 .mu.M usually produced only the phase of decreased excitability; occasionally a biphasic response was noted.