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.


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.
Main Line Health Heart Center and Lankenau Institute for Medical Research, 100 Lancaster Ave, Wynnewood, PA, 19096, USA. yanganxin@mlhheart.org
Gan-Xin
GX
Yan
Ajay
A
Joshi
Donglin
D
Guo
Thinn
T
Hlaing
Jack
J
Martin
Xiaoping
X
Xu
Peter R
PR
Kowey
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials; D000208:Acute Disease; D000818:Animals; D005117:Cardiac Complexes, Premature / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004562:Electrocardiography; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000473:pathology; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000150:complications* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000502:physiology; D010477:Perfusion; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000503:physiopathology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D015761:4-Aminopyridine