Carvedilol suppresses ventricular arrhythmia in a pressure over-load rabbit model through relieving transmural dispersion of repolarization with long-term administration

Abstract

ObjectiveTo investigate the effects of carvedilol (CVD) on transmural dispersion of repolarization (TDR) and arrhythmia in pressure over-load rabbits. MethodsLeft ventricular hypertrophied (LVH) rabbit models were established by pressure over-load; All animal models were assigned into CVD group or LVH group randomly. The action potentials of endocardium, epicardium and transmural ECG of arterially perfused left ventricular preparations were recorded concurrently. Action potential duration (APD), TDR, ventricular arrhythmia and ultrasonic parameters, ratio of LVM to body weight (LVMI) were compared correspondingly. The stable plasma concentration of carvedilol in CVD group was detected by HPLC. APD, TDR and arrhythmia of LVH models were compared just pre- or post-perfusion with stable concentration of CVD. ResultsIn Contrast with values in LVH group, LVEF of CVD group were significantly elevated while the LVMI was remarkably reduced, TDRs were significantly shortened, and ratio of ventricular arrhythmia was lowered remarkably. No significant difference of APD, TDR and ratio of arrhythmia was found preor post-perfusion at stable plasma concentration of CVD. ConclusionCVD can ameliorate the structure and function of pressure over-load ventricles; CVD contributes to the improvement of ventricular arrhythmia associated with its long-term effect on APD, TDR shortening, whereas has nothing to do with its transient function on ionic channel blockade.