Cardioprotective effects of low-dose combination therapy with a statin and an angiotensin receptor blocker in a rat myocardial infarction model.
Cardioprotective effects of low-dose combination therapy with a statin and an angiotensin receptor blocker in a rat myocardial infarction model.
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DOI：
10.1016/j.jjcc.2011.07.013
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发表时间：
2012
影响因子：
2.5
通讯作者：
Ryoichi Sohma;Teruo Inoue;S. Abe;I. Taguchi;M. Kikuchi;Shigeru Toyoda;Takuo Arikawa;Y. Hikichi;S. Sanada;H. Asanuma;M. Kitakaze;K. Node
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文献类型：
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作者：
Ryoichi Sohma;Teruo Inoue;S. Abe;I. Taguchi;M. Kikuchi;Shigeru Toyoda;Takuo Arikawa;Y. Hikichi;S. Sanada;H. Asanuma;M. Kitakaze;K. Node
目的他汀类药物可减轻血管紧张素ii诱导的心肌细胞肥大，这可能增加肾素-血管紧张素系统抑制对缺血心脏的保护作用。在这项研究中，我们用大鼠心肌梗死模型研究了低剂量辛伐他汀和低剂量氯沙坦联合治疗的心脏保护作用。方法采用左前降支结扎术致心肌梗死大鼠，随机分为对照组（n=8）、氯沙坦3mg/kg/d组（n=8）、辛伐他汀2mg/kg/d组（n=8）、氯沙坦3mg/kg/d +辛伐他汀2mg/kg/d组（n=8）。每次治疗均于冠脉结扎当日开始，28天后测量血流动力学、心肌血流量和梗死面积。结果与其他3个治疗组相比，对照组血压、心率、左心室收缩压和舒张末期压均无显著差异。与氯沙坦和辛伐他汀组相比，对照组左室压峰值正一阶导数（LV dP/dt峰值）相当。氯沙坦联合辛伐他汀组的峰值LV dP/dt高于对照组（p<0.05）。心肌血流量、左室重量、梗死面积均无明显变化。结论氯沙坦3mg/kg/d联合辛伐他汀2mg/kg/d治疗可改善大鼠心肌梗死模型左心室收缩功能，但不能单独使用氯沙坦或辛伐他汀。结果表明，他汀类药物与血管紧张素受体阻滞剂联合使用可能具有有益的心脏保护作用，即使每种药物的剂量都很低。
PURPOSEStatins attenuate angiotensin II-induced myocyte hypertrophy and this might increase the cardioprotective effects of renin–angiotensin system inhibition in the ischemic heart. In this study, we investigated the cardioprotective effects of combination therapy with low-dose simvastatin and low-dose losartan using a rat myocardial infarction model.METHODSMyocardial infarction was created in rats by left anterior descending artery ligation, and the animals were randomly allocated to one of four groups: control (n=8), losartan 3mg/kg/day (n=8), simvastatin 2mg/kg/day (n=8), and losartan 3mg/kg/day plus simvastatin 2mg/kg/day (n=8). Each treatment was started on the day of coronary ligation, and hemodynamics, myocardial blood flow, and infarct size were measured after 28 days.RESULTSBlood pressure, heart rate, and left ventricular systolic and end-diastolic pressures were not significantly different comparing the control group with the 3 other treatment groups. The peak positive first derivative of left ventricular pressure (peak LV dP/dt) was equivalent comparing the control group with the losartan and simvastatin groups. However, the peak LV dP/dt was greater in the losartan plus simvastatin group than in the control group (p<0.05). Myocardial blood flow, left ventricular weight, and infarct size were not significantly altered by the 3 treatments.CONCLUSIONSTreatment with 3mg/kg/day losartan plus 2mg/kg/day simvastatin but not losartan or simvastatin alone improved left ventricular systolic function in a rat myocardial infarction model. The result suggests that statins given in combination with angiotensin receptor blockers might have beneficial cardioprotective effects, even at low-doses for each agent.