He Li, Xiao Jianmin, Fu Hui, Du Guangsheng, Xiao Xing, Zhang Cuntai, Gu Ye, Ma Yexin
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.
J Huazhong Univ Sci Technolog Med Sci. 2012 Jun;32(3):334-339. doi: 10.1007/s11596-012-0058-y. Epub 2012 Jun 9.
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.
本研究的目的是探讨氧化应激对阿霉素诱导的心肌病家兔室性心律失常的影响以及氧化应激与室性心律失常之间的关系。40只日本白兔随机分为四组（每组n = 10）：对照组、美托洛尔（一种选择性β1受体阻滞剂）组、卡维地洛（一种非选择性β阻滞剂/α-1阻滞剂）组和阿霉素组。阿霉素、美托洛尔和卡维地洛组的家兔通过耳缘静脉每周两次静脉注射盐酸阿霉素（1 mg/kg），持续8周，以建立阿霉素诱导的心肌病模型。对照组家兔通过耳缘静脉给予等量的生理盐水。美托洛尔组和卡维地洛组的家兔随后分别以5 mg/kg/d的剂量灌胃给予美托洛尔和卡维地洛，持续2个月，而阿霉素组和对照组的家兔则以与美托洛尔组和卡维地洛组相同的方式给予等量的生理盐水。通过超声心动图测量左心室舒张末期内径（LVEDd）和左心室射血分数（LVEF）。检测血浆N末端B型利钠肽原（NT-proBNP）、丙二醛（MAD）和超氧化物歧化酶（SOD）水平。用台氏液灌注左心室楔形标本。记录跨壁心电图、心外膜（Epi）和心内膜（Endo）的跨壁动作电位、跨壁复极离散度（TDR），并在快速周期长度下获得触发活动和室性心律失常的发生率。结果显示，与对照组相比，阿霉素组的TDR、血清MDA和NT-proBNP水平升高，LVEF和血清SOD水平降低。阿霉素组触发活动和室性心律失常的发生率显著高于对照组（P<0.05）。与阿霉素组相比，卡维地洛组血清SOD水平和LVEF显著升高；TDR、血清MDA和NT-proBNP水平显著降低；触发活动和室性心律失常的发生率明显降低（P<0.05）。阿霉素组和美托洛尔组之间的MDA和SOD水平、LVEF、TDR以及触发活动和室性心律失常的发生率无显著差异。结论：卡维地洛可能抑制阿霉素诱导的心肌病家兔的触发活动和室性心律失常，这与氧自由基的减少有关。
