ypertensive left ventricular hypertrophy (LVH) is associated with an enhanced incidence of ventricular arrhythmia and an increased risk of sudden cardiac death. [1][2][3] Although in vitro studies of hypetensive LVH have proposed various electrophysiological abnormalities (ie, impulse formation 4,5 and conduction, 6-8 and repolarization abnormalities 9 ) as arrhythmogenic substrates, it remains unclear how these factors directly relate to the vulnerability to ventricular tachyarrhythmia in the in vivo whole heart. In other words, it remains poorly understood just how these electrophysiological abnormalities develop and increase the vulnerability to ventricular tachyarrhythmia with progression of LVH. The arrhythmogenic potential in hypertensive LVH may be multifactorial, but susceptibility to ventricular tachycardia (VT) induction has not been simultaneously investigated in the same LVH preparations, and therefore the relationships between various underlying arrhythmogenic mechanisms and VT attack have not been clarified. A clear understanding of this pathophysiological linkage is essential for determining the therapeutic target for prevention of fatal ventricular tachyarrhythmia. To investigate this issue, we used Dahl salt-sensitive hypertensive rats in which concentric LVH develops in a relatively short period. 10 Our preliminary study using this LVH model revealed that polymorphic VT was induced by programmed electrical stimulation, as shown by Coste et al in their clinical report. 11 Thus, the objectives of this study were first, to quantify the vulnerability of VT to programmed extrastimuli, and the changes it undergoes during the development of hypertensive LVH; second, to clarify how this vulnerability of VT relates to arrhythmogenic substrates (ie, conduction disturbances defined by a decrease in conduction velocity and an increase in the fractionation of QRS complex, and repolarization abnormalities defined by increases in the absolute refractory period and monophasic action potential (MAP) duration); and third, to examine how cellular electrophysiological remodeling relates to conduction and repolarization abnormalities of the whole heart during the progress of LVH. For these purposes, we performed programmed electrical stimulation to induce VT at 3 different observation periods in Dahl salt-sensitive (S) rats and -resistant (R) rats, and compared the vulnerability to VT with the conduction velocity and the degree of inhomogeneous conduction evaluated by wavelet analysis, 12,13 duration of MAP, 14 and absolute refractory period. In addition, myocytes were isolated from the same hearts, and patch-clamp analysis was performed for evaluation of resting membrane potential (RMP) and action potential (AP), as well as sodium (INa), calcium (ICa), and transient outward potassium currents (Ito). 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 ResultsDahl salt...

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