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 electrophyriological actions. We studied the effects of LPC on passive and active membrane properties and on repolarization in the Purkinje fibers of sheep using multiple microelectrodes: one for intracellular current injection and the other for transmembrane voltage (V_) recording. Synthetic 1palmitoyl LPC (10-50 /IM) was used in normal Tyrode's solution. These concentration* are presumably equivalent to those of free LPC in ischemic myocardium. At a low [LPC]O of 10-20 jtM, cable analysis showed increased membrane (R«) and longitudinal (Ri) resistances (P< 0.010 and <0.013, respectively); LPC increased the length (K*) and time (Tm) constants (P < 0.018 and <0.010, respectively) with the balance between R. and Ri determining input resistance. The increased R», 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 fiM decreased the maximal rate of rise of phase 0 ( V J (P < 0.001), even during the phase of increased excitability, and depressed and flattened the VTM vs. charge relationships. This depression of the sodium system resulted in a phase of decreased excitability and often inexcitability despite Rm being maintained near or somewhat 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, two stable steady states at resting and plateau Vn, or one steady state at a low Vm. Abnormal sustained rhythmic activity was observed commonly both at high and low Vm. High [LPCJo of over 40 /IM usually produced only the phase of decreased excitability, although occasionally a biphasic response was noted. CircRea49:16-30, 1981