AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 281: H1968-H1975, 2001;
0363-6135/01 $5.00
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Vol. 281, Issue 5, H1968-H1975, November 2001

Ventricular hypertrophy amplifies transmural repolarization dispersion and induces early afterdepolarization

Gan-Xin Yan1, Seth J. Rials3, Ying Wu1, Tengxian Liu1, Xiaoping Xu1, Roger A. Marinchak1,2, and Peter R. Kowey1,2

1 Main Line Health Heart Center, Wynnewood 19096; 2 Jefferson Medical College, Philadelphia, Pennsylvania 19107; and 3 HeartCare Incorporated, Columbus, Ohio 43215

The effects of left ventricular hypertrophy (LVH) on the generation of phase 2 early afterdepolarization (EAD) and transmural dispersion of repolarization (TDR) were assessed using arterially perfused rabbit ventricular wedge preparations. Transmembrane action potentials from epicardium, subendocardium, and endocardium were simultaneously recorded together with a transmural ECG. Transmural action potential duration (APD) was also mapped. LVH (renovascular hypertension model) produced significant prolongation in ventricular APD and QT interval. Preferential APD prolongation in subendocardium and endocardium was associated with a marked increase in TDR. Phase 2 EADs were generated from subendocardium or endocardium in all LVH rabbits (15 of 15) in the absence of APD prolonging agents at basic cycle lengths of 2,000-4,000 ms. Phase 2 EAD could produce "R on T" extrasystoles, initiating polymorphic ventricular tachycardia (VT). This study provides the first direct evidence from intracellular recordings that phase 2 EAD could be generated from rabbit intact hypertrophied LV wall in the absence of APD prolonging agents, resulting in R on T extrasystoles capable of initiating polymorphic VT under enhanced TDR.

action potential; ventricular tachycardia; epicardium; endocardium


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