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首页> 外文期刊>American Journal of Physiology >Effects of pre-, peri-, and postmyocardial infarction treatment with losartan in rats: effect of dose on survival, ventricular arrhythmias, function, and remodeling.
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Effects of pre-, peri-, and postmyocardial infarction treatment with losartan in rats: effect of dose on survival, ventricular arrhythmias, function, and remodeling.

机译：氯沙坦对大鼠心肌梗死前，周围和后的影响：剂量对存活率，室性心律失常，功能和重塑的影响。

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摘要

Angiotensin receptor blockers (ARBs) reduce adverse left ventricular (LV) remodeling and improve LV function and survival when started postmyocardial infarction (MI). ARBs also reduce ventricular arrhythmias during ischemia-reperfusion injury when started pre-MI. No information exists regarding their efficacy and safety when started pre-MI and continued peri- and post-MI. We evaluated whether the ARB losartan improves the outcome when started pre-MI and continued peri- and post-MI. Male Wistar rats (n = 502) were treated for 7 days pre-MI with losartan at a high dose (30 mg.kg(-1).day(-1)), progressively increasing dose (3 mg.kg(-1).day(-1) increased to 10 mg.kg(-1).day(-1) 10 days and 30 mg.kg(-1).day(-1) 20 days post-MI), or no treatment. Ambulatory systolic blood pressure and Holter monitoring were performed for 24 h post-MI. Echocardiography was done 30 days post-MI, and LV remodeling, cardiac hemodynamics, and fetal gene expression were assessed 38 days post-MI. High-dose losartan reduced 24-h post-MI survival compared with the progressive dose and control (21.9% vs. 36.6% and 38.1%, P = 0.033 and P = 0.009, respectively). This was associated with greater hypotension in the high dose and no change in ventricular arrhythmias in all groups. In 24-h post-MI survivors, the progressive dose group had reduced mortality from 24 h to 38 days (8.5% vs. 28.6% for control vs. 38.9% for high dose, P = 0.032 and P = 0.01, respectively). Survivors of both losartan groups demonstrated improved LV remodeling, cardiac hemodynamics, preserved GLUT-4, and reduced cardiac fetal gene expression. Pretreatment with ARBs does not reduce 24-h post-MI ventricular arrhythmias or survival, and high doses increase mortality by causing excessive hypotension. In 24-h post-MI survivors, progressively increasing doses of losartan have multiple beneficial effects, including improved survival.
机译：当开始心肌梗塞（MI）时，血管紧张素受体阻滞剂（ARB）可以减少不良的左心室（LV）重塑并改善LV功能和存活率。 MI前开始时，ARBs还可以减少缺血再灌注损伤期间的室性心律失常。在开始心梗前以及持续心梗后和心梗后，尚无有关其疗效和安全性的信息。我们评估了开始心梗前以及持续心梗后和心梗后，ARB氯沙坦是否能改善预后。雄性Wistar大鼠（n = 502）在心梗前用高剂量（30 mg.kg（-1）.day（-1））的氯沙坦治疗，并逐渐增加剂量（3 mg.kg（-1） ）.day（-1）增加至MI后20天的10 mg.kg（-1）.day（-1）10天和30 mg.kg（-1）.day（-1）20天，或不进行治疗。 MI后24小时进行动态收缩压和动态心电图监测。 MI后30天进行超声心动图检查，MI后38天评估左心室重塑，心脏血液动力学和胎儿基因表达。与渐进剂量和对照组相比，大剂量氯沙坦降低了MI患者的24小时生存率（分别为21.9％，36.6％和38.1％，P = 0.033和P = 0.009）。这与高剂量低血压相关，所有组室性心律不齐均无变化。在心梗后24小时生存者中，渐进剂量组的死亡率从24小时降低至38天（对照组为8.5％，对照组为28.6％，高剂量组为38.9％，分别为P = 0.032和P = 0.01）。氯沙坦两组的幸存者均表现出改善的左室重构，心脏血流动力学，保留的GLUT-4和减少的心脏胎儿基因表达。用ARB进行预处理不会降低MI后24小时的室性心律不齐或存活率，高剂量会引起过度的低血压而增加死亡率。在心梗后24小时生存者中，逐渐增加剂量的氯沙坦具有多种有益作用，包括改善生存率。

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