The importance of the electrophysiologic substrates in the development of ventricular tachyarrhythmias.

Our electrophysiologic findings are summarized in Table 3. In our animal model of chronic myocardial infarction, induced sustained ventricular tachyarrhythmias occur from 3 days to months following the infarction procedure. Isolated tissues removed from the infarcted region in these animals and studied (table: see text) in vitro reveal regions of slow conduction and local conduction block. These characteristics also persist over this time period and appear to be the substrate responsible for the reentrant excitation at the basis of the ventricular tachyarrhythmias. Our cellular electrophysiologic studies indicate the mechanisms responsible for the abnormal conduction change with time. Up to approximately 2 weeks following the infarction procedure, cellular membrane depolarization is depressed and cell-to-cell electrical continuity is decreased. Both of these factors probably contribute to the slow conduction. Depression in membrane excitability does not seem to play a role. Although an increased dispersion in refractoriness probably contributes to the inducibility of ventricular reentry due to an enhanced propensity for a premature impulse to undergo functional block in one region while continuing to conduct in another region. At two weeks and beyond, action potential depolarization has returned to normal. At this time the sole contributor to the abnormal conduction appears to be cellular electrical uncoupling. Two possibilities for the cause of this cellular uncoupling are as follows: First, the low resistance gap junctions between cells may be modified in the infarcted region causing an increase in internal axial resistance. Another possibility is that the fibrotic matrix in which the surviving cells in the mottled infarct are distributed may contribute to an increase in extracellular resistance as compared to normal myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)