EFFECTS OF CONTRACTION-EXCITATION FEEDBACK ON ELECTROPHYSIOLOGY AND ARRHYTHMOGENESIS IN RABBITS WITH EXPERIMENTAL LEFT-VENTRICULAR HYPERTROPHY

Objective: The aim was to investigate the influence of contraction-excitation feedback on myocardial electrophysiology and arrhythmia susceptibility in the setting of experimental left ventricular hypertrophy. Methods: New Zealand White rabbits with perinephritis hypertension were used. With the hearts perfused in vitro, left ventricular monophasic action potential duration and local effective refractory periods were determined at three sites, namely the anterior, apical, and posterior wall, together with ventricular tachycardia inducibility and ventricular fibrillation threshold under different loading conditions. Results: The left ventricular dry weight to body weight ratio was increased by 31% in the hypertrophied group (3.863 x 10(-4), v 2.955 X 10(-4) in the controls). Left ventricular hypertrophy was associated with prolongation of action potential duration when the left ventricle was not loaded and under normal loading conditions. Changing from unloaded Langendorff to baseline working heart perfusion resulted in a consistent decrease in action potential duration and effective refractory period at all left ventricular sites in both hypertrophied and control hearts. Subsequent manipulations of myocardial loading resulted in decreases in action potential duration and effective refractory period in both groups of hearts. Ventricular tachycardia could not be induced in any heart in Langendorff mode. Under different increased loading conditions, a total of four hypertrophied hearts (44%) became inducible, while control hearts remained non-inducible. The ventricular fibrillation threshold under conditions of increased load tended to be lower in the hypertrophied hearts than the control hearts; in the setting of increased preload the hypertrophied group showed significantly increased vulnerability to ventricular fibrillation (median threshold currents 35 mA v > 100 mA, p < 0.05). Conclusions: Left ventricular hypertrophy is associated with a prolongation of action potential duration and effective refractory period and an increased arrhythmia susceptibility in the setting of increased myocardial loading. There were no marked differences between the groups in the magnitude of the changes in action potential duration, effective refractory period, or dispersion of repolarisation and refractoriness resulting from manipulations of myocardial loading that could have been implicated in the increased arrhythmia susceptibility of the hypertrophied hearts during changes in load.