The beneficial effects of ivabradine against myocardial damage induced by isoproterenol in rats

S. Polat, Miray Altuntas, M. Gunata, A. Polat, L. Tanrıverdi, A. Yıldız, M. Durhan, N. Vardı, Y. Cigremis, H. Acet, H. Parlakpınar
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Abstract

We aimed to investigate the potential benefits of two doses of ivabradine (IVA)-an If sodium channel blocker against isoproterenol (ISO)-induced myocardial damage in rats.The rats were randomly divided into 4 groups: Control group (n=8); Saline was administered, ISO group (n=12); 150 mg/kg ISO was administered for 2 days, ISO+IVA (1 mg/kg) group (n=12); 1 mg/kg IVA was administered for 4 days in addition to ISO. ISO+IVA (10 mg/kg) group (n=12): 10 mg/kg IVA was administered for 4 days in addition to ISO. Thereafter, hemodynamic, histopathological, and biochemical studies were performed. In the ISO+IVA (1 mg/kg) and ISO+IVA (10 mg/kg) groups, ISO-induced myocardial changes including an increase in density of granulation tissue and degenerated cardiomyocyte were equally decreased. HR was mildly reduced, and arterial blood pressures were slightly increased in the IVA-treated groups versus the ISO group. In the hearts of IVA-treated groups, malondialdehyde (MDA) levels were significantly reduced and glutathione (GSH) level and catalase (CAT) activity were mildly increased compared to the ISO group. Elevation of GSH and CAT activity were more pronounced in the ISO+IVA (10 mg/kg) group. Our results indicate that both 1 mg/kg and 10 mg/kg doses of IVA are effective against heart damage induced by ISO via its negative chronotropic, anti-oxidant (dose-dependent), anti-inflammatory and anti-degenerative properties.
伊伐布雷定对异丙肾上腺素所致大鼠心肌损伤的有益作用
我们的目的是研究两种剂量的伊伐布雷定(IVA)和If钠通道阻滞剂对异丙肾上腺素(ISO)诱导的大鼠心肌损伤的潜在益处。将大鼠随机分为4组:对照组(n=8);给予生理盐水,ISO组(n=12);150 mg/kg ISO给药2 d, ISO+IVA (1 mg/kg)组(n=12);在ISO基础上给予IVA 1 mg/kg,连续4天。ISO+IVA (10 mg/kg)组(n=12):在ISO基础上给予10 mg/kg IVA,连续4 d。然后进行血流动力学、组织病理学和生化研究。在ISO+IVA (1 mg/kg)和ISO+IVA (10 mg/kg)组中,ISO诱导的心肌变化,包括肉芽组织密度的增加和心肌细胞的退化,都同样减少。与ISO组相比,iva治疗组HR轻度降低,动脉血压略有升高。与ISO组相比,iva处理组心脏丙二醛(MDA)水平显著降低,谷胱甘肽(GSH)水平和过氧化氢酶(CAT)活性轻度升高。在ISO+IVA (10 mg/kg)组,GSH和CAT活性升高更为明显。我们的研究结果表明,1mg /kg和10mg /kg剂量的IVA通过其负变时性、抗氧化(剂量依赖性)、抗炎和抗退行性对ISO引起的心脏损伤有效。
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