Phase 2 reentry as a mechanism of initiation of circus movement reentry in canine epicardium exposed to simulated ischemia

Objectives: Myocardial ischemia results in an early phase of arrhythmias that primarily involves reentrant mechanisms. However, the trigger that initiates sentry remains unknown. We studied the initiation of reentry attending the development of electrical heterogeneity during simulated ischemia in isolated canine right ventricular subepicardium. Methods: Preparations consisted of thin epicardial sheets in which action potentials were recorded at 4 sites with intracellular microelectrodes. Tissues were superfused with a hyperkalemic, hypoxic and acidotic 'ischemic' solution. Results: Simulated ischemia produced a 40-70% abbreviation of the action potential at some epicardial sites but not others, primarily by suppressing development of the action potential plateau (or dome). This typically created a marked dispersion of repolarization within the preparation. Local re-excitation ensued when the action potential dome propagated from sites where it was maintained to sites where it was abolished. This mechanism, termed 'phase 2 reentry', produced an extrasystole which then initiated one or more cycles of circus movement reentry. Tachycardias consisting of repetitive reentry occurred in larger tissues. The window for sentry occurred over a range of stimulation rates that shifted to faster rates as ischemia progressed. The transient outward current blocker, 4-aminopyridine, restored the dome at all sites by reversing the ischemia-induced abbreviation of the action potential. Thus, block of the transient outward current restored electrical homogeneity and abolished all reentrant activity within the epicardial preparations. Conclusion: Our results implicate phase 2 reentry as a new mechanism for genesis of extrasystoles during simulated ischemia and identify this mechanism as a trigger of circus movement reentry. Validation of this hypothesis awaits the results of future studies using high-resolution recording techniques.