The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with
adriamycin-induced
cardiomyopathy and the relationship between oxidative stress and ventricular
arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group,
metoprolol (a selective β1 receptor blocker) group,
carvedilol (a nonselective β blocker/α-1 blocker) group and
adriamycin group. Models of
adriamycin-induced
cardiomyopathy were established by intravenously injecting
adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the
adriamycin,
metoprolol and
carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the
metoprolol and
carvedilol groups were then intragastrically administrated
metoprolol (5 mg/kg/d) and
carvedilol (5 mg/kg/d) respectively for 2 months, while those in the
adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and
carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro
B-type natriuretic peptide (
NT-proBNP),
malondialdehyde (MAD) and
superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with
Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and
NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the
adriamycin group compared with the control group. The incidences of triggered activity and ventricular
arrhythmia were significantly higher in the
adriamycin group than those in the control group (P<0.05). In the
carvedilol group as compared with the
adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and
NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular
arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular
arrhythmia between the
adriamycin group and the
metoprolol group. It was concluded that
carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with
adriamycin-induced
cardiomyopathy, which is related to the decrease in
oxygen free radials.