Phase 2 Reentry as a Trigger to Initiate Ventricular Fibrillation During Early Acute Myocardial Ischemia

Abstract

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 ϩ ] 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 ϩ ] 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 ϩ30 mV in the group with phase 2 reentry-related R-on-T extrasystoles were 32.2Ϯ1.3 mV and 30.3Ϯ0.5 pA/pF (nϭ7), respectively, significantly greater than those (24.0Ϯ1.8 mV and 23.2Ϯ1.0 pA/pF) in the group without the extrasystoles (nϭ8, PϽ0.01). 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.

Brugada syndrome and ischemia-induced ST-segment elevation. Similarities and differences

“…Loss of the action potential dome giving rise to "true" ST-segment elevation and closely coupled phase 2 reentrant extrasystoles may more likely develop within the border zone of the ischemic region [26] or during low-flow ischemia, conditions at which K + accumulation leading to membrane depolarization and thus to a reduction of the Epi notch (due to inactivation of I to ) and slowing of conduction (due to inactivation of I Na ) is minimized.…”

Allicin inhibits transient outward potassium currents in mouse ventricular myocytes

“…It has been confirmed that a prominent I to is important in physiological and pathophysiological process (37)(38)(39)(40)(41). The high incidence of phase 2 reentry and ventricular fibrillation during myocardial ischemia was partly due to the prominent I to -mediated epicardial AP dome (42). In patients with coronary heart disease, the incidence of sudden mortality in men was significantly higher compared with that in women (43,44).…”

Ischemia-Induced Prominent J Waves in a Patient with Brugada Syndrome

“…Numerous ionic currents, calcium cycling, signal transduction, and so forth would be altered during the myocardial ischemia but, both channelopathy and ischemia may share common mechanisms which result in such prominent J waves and coved type ST elevation, which may be risk factors which develop into ventricular fibrillation due to phase 2 reentry (8,13,18,19).…”