Ventricular hypertrophy amplifies transmural repolarization dispersion andinduces early afterdepolarization

The effects of left ventricular hypertrophy (LVH) on the generation of phas e 2 early afterdepolarization (EAD) and transmural dispersion of repolariza tion (TDR) were assessed using arterially perfused rabbit ventricular wedge preparations. Transmembrane action potentials from epicardium, subendocard ium, and endocardium were simultaneously recorded together with a transmura l ECG. Transmural action potential duration (APD) was also mapped. LVH (ren ovascular hypertension model) produced significant prolongation in ventricu lar APD and QT interval. Preferential APD prolongation in subendocardium an d endocardium was associated with a marked increase in TDR. Phase 2 EADs we re generated from subendocardium or endocardium in all LVH rabbits (15 of 1 5) 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 poly morphic 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 a gents, resulting in R on T extrasystoles capable of initiating polymorphic VT under enhanced TDR.