Comprehensive Analyses of Arrhythmogenic Substrates and Vulnerability to Ventricular Tachycardia in Left Ventricular Hypertrophy in Salt-Sensitive Hypertensive Rats

BACKGROUND: The contribution of conduction disturbances to susceptibility to ventricular tachycardia (VT) has not been directly examined in the process of left ventricular hypertrophy (LVH). METHODS AND RESULTS: Dahl salt-sensitive (S) and -resistant rats were raised on a high-salt diet. After echocardiography, a fractionation study was conducted using wavelet transform analysis, which reflects conduction disturbances, recording of monophasic action potential (MAP), measurement of conduction velocity, and programmed extrastimuli for the induction of VT, as well as patch-clamp analysis at 10, 13 and 16 weeks (W) (n=7, each). Systolic blood pressure, wall thickness and MAP duration significantly increased at 10W in S rats, whereas conduction velocity decreased and MAP duration and the power of wavelet transform increased at 13W and 16W. Paired extrastimuli induced polymorphic VT only at 13W and 16W in S rats. VT frequency correlated inversely with conduction velocity and positively with MAP duration. Power of wavelet transform correlated negatively with conduction velocity and positively with VT vulnerability. The patch-clamp study revealed that the action potential duration significantly increased in S rats with aging, and correlated with MAP duration. CONCLUSIONS: Latently progressing slow and inhomogeneous conduction, as well as a repolarization abnormality, may contribute to VT vulnerability in hypertensive LVH.