Department of Cardiovascular Surgery, Inonu University, Malatya, Turkey.
Hum Exp Toxicol. 2012 Sep;31(9):945-54. doi: 10.1177/0960327112438288. Epub 2012 Feb 21.
The aim of this study was to investigate the possible effects of ivabradine against doxorubicin (DOX)-induced cardiotoxicity in rats using hemodynamic parameters (electrocardiogram, heart rate (HR), and blood pressure), biochemical markers of oxidative stress, lactate dehydrogenase, aspartate transaminase, creatine kinase-MB, and histopathological analyses both in serum and tissue specimens. A total of 28 female rats were randomly assigned to 4 groups: (a) control (n = 6 rats), (b) DOX group (n = 7 rats), (c) DOX + ivabradine-treated group (n = 8 rats), and (d) ivabradine group (n = 7 rats). When the means of the four groups were compared, there was only a significant difference in the level of HR (p < 0.05). DOX treatment caused more HR elevation when compared to the control group, whereas ivabradine application after DOX treatment significantly reduced HR levels. Cardiomyocytes were revealed as normal histology in the light of both hematoxylin and eosin staining and immunostaining methods (caspase-3 and bcl-2) in all groups. The present study reported the therapeutic effects of ivabradine against DOX-induced cardiotoxicity accompanied by the hemodynamic and biochemical parameters.
本研究旨在通过血流动力学参数（心电图、心率（HR）和血压）、氧化应激的生化标志物、乳酸脱氢酶、天门冬氨酸氨基转移酶、肌酸激酶同工酶以及血清和组织标本的组织病理学分析，研究伊伐布雷定对大鼠多柔比星（DOX）诱导的心脏毒性的可能作用。总共 28 只雌性大鼠被随机分配到 4 组：（a）对照组（n = 6 只大鼠）、（b）DOX 组（n = 7 只大鼠）、（c）DOX + 伊伐布雷定治疗组（n = 8 只大鼠）和（d）伊伐布雷定组（n = 7 只大鼠）。当比较四组的平均值时，只有 HR 水平存在显著差异（p < 0.05）。与对照组相比，DOX 治疗导致 HR 升高更为明显，而 DOX 治疗后应用伊伐布雷定可显著降低 HR 水平。根据苏木精和曙红染色以及免疫染色方法（caspase-3 和 bcl-2），所有组的心肌细胞均表现为正常组织学。本研究报道了伊伐布雷定对 DOX 诱导的心脏毒性的治疗作用，同时伴有血流动力学和生化参数的改善。
