This Article Full Text Full Text (PDF) All Versions of this Article: 110/9/1036    most recent 01.CIR.0000140258.09964.19v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yan, G.-X. Articles by Kowey, P. R. Search for Related Content PubMed PubMed Citation Articles by Yan, G.-X. Articles by Kowey, P. R. Related Collections Arrythmias-basic studies

(Circulation. 2004;110:1036-1041.)
© 2004 American Heart Association, Inc.

Original Articles

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

Gan-Xin Yan, MD PhD; Ajay Joshi, MD; Donglin Guo, MD PhD; Thinn Hlaing, MD; Jack Martin, MD; Xiaoping Xu, PhD; Peter R. Kowey, MD

From Main Line Health Heart Center and Lankenau Institute for Medical Research, Wynnewood, Pa (G.X.Y., A.J., D.G., T.H., J.M., X.X., P.R.K.); The First Hospital of Xi’an Jiaotong University, Xi’an, China (G.X.Y.); and Lankenau Institute for Medical Research, Wynnewood, Pa (G.X.Y., P.R.K.).

Correspondence to Dr Gan-Xin Yan, Main Line Health Heart Center, 100 Lancaster Ave, Wynnewood, PA, 19096. E-mail yanganxin{at}mlhheart.org

Received September 17, 2003; de novo received March 2, 2004; revision received April 8, 2004; accepted April 12, 2004.

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.

Key Words: ischemia • arrhythmia • electrocardiography

This article has been cited by other articles:

				C. Antzelevitch Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2024 - H2038. [Abstract] [Full Text] [PDF]

				K. A. Ellenbogen, J. H. Levine, R. D. Berger, J. P. Daubert, S. L. Winters, E. Greenstein, A. Shalaby, A. Schaechter, H. Subacius, A. Kadish, et al. Are Implantable Cardioverter Defibrillator Shocks a Surrogate for Sudden Cardiac Death in Patients With Nonischemic Cardiomyopathy? Circulation, February 14, 2006; 113(6): 776 - 782. [Abstract] [Full Text] [PDF]