Phase 2 reentry as a trigger to initiate ventricular fibrillation during early acute myocardial ischemia.

BACKGROUND Phase 2 reentry caused by heterogeneous loss of the transient outward potassium current (I(to))-mediated epicardial action potential (AP) dome can produce a closely coupled R-on-T extrasystole leading to ventricular fibrillation (VF) under conditions of ST-segment elevation unrelated to ischemia. The present study examined the role of phase 2 reentry in the initiation of VF during early myocardial ischemia. METHODS AND RESULTS Regional myocardial ischemia was produced in an isolated, arterially perfused canine right ventricular wedge preparation. Transmembrane APs from 2 epicardial sites at each side of the ischemic border were simultaneously recorded together with measurements of extracellular potassium concentration ([K+]o) and a transmural ECG. Loss of the I(to)-mediated epicardial AP dome in the ischemic zone but not in the perfused tissue resulted in phase 2 reentry and associated R-on-T extrasystoles capable of initiating VF in 7 of 15 preparations during the first 3 to 9 minutes of myocardial ischemia, with marked ST-segment elevation and [K+]o accumulation. The I(to) and phase 1 magnitude of epicardium contributed importantly to the onset of VF. Phase 1 magnitude and I(to) density at +30 mV in the group with phase 2 reentry-related R-on-T extrasystoles were 32.2+/-1.3 mV and 30.3+/-0.5 pA/pF (n=7), respectively, significantly greater than those (24.0+/-1.8 mV and 23.2+/-1.0 pA/pF) in the group without the extrasystoles (n=8, P<0.01). CONCLUSIONS Acute regional myocardial ischemia results in markedly heterogeneous loss of I(to)-mediated epicardial AP domes across the ischemic border, leading to phase 2 reentry. Phase 2 reentry can in turn produce an R-on-T extrasystole capable of initiating VF.