Effect of oxidative stress on ventricular arrhythmia in rabbits with adriamycin-induced cardiomyopathy.
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.
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Cardiology, Puai Hospital, Wuhan, 430033, China.
Li
L
He
Department of Cardiology, Dongguan Taiping Hospital, Dongguan, 523905, China.
Jianmin
J
Xiao
Department of Pharmacology, Guangdong Medical College, Guangzhou, 523808, China.
Hui
H
Fu
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Guangsheng
G
Du
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Xing
X
Xiao
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Cuntai
C
Zhang
Department of Cardiology, Puai Hospital, Wuhan, 430033, China.
Ye
Y
Gu
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. drmayexin@sina.com.
Yexin
Y
Ma
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D000903:Antibiotics, Antineoplastic; D002227:Carbazoles / Q000008:administration & dosage*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D000077261:Carvedilol; D004317:Doxorubicin; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects*; D011412:Propanolamines / Q000008:administration & dosage*; D011817:Rabbits; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; D000903:Antibiotics, Antineoplastic; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D004317:Doxorubicin; D008790:Metoprolol