Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction
Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction
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DOI：
10.1007/s00380-014-0589-1
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发表时间：
2016-01-01
影响因子：
1.5
通讯作者：
Gogenur, Ismail
中科院分区：
文献类型：
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作者：
Ekelof, Sarah V.;Halladin, Natalie L.;Gogenur, Ismail
直接经皮冠状动脉介入治疗是治疗急性冠状动脉闭塞的有效方法。然而，心肌缺血-再灌注损伤是目前手术不可避免的后果。氧化应激在缺血-再灌注损伤的发展中起核心作用。褪黑激素是一种内源性激素，通过抗氧化机制发挥作用，可能减轻心肌损伤。实验研究的目的是在猪闭胸再灌注梗死模型中检查褪黑素的心脏保护作用。将总共20头长白猪随机分配至200 mg（0.4 mg/mL）褪黑激素或安慰剂（生理盐水）剂量组。通过冠状动脉内和静脉内进行干预。通过心血管磁共振成像离体测定动脉瘤的大小、危险区域和微血管阻塞。计算心肌挽救指数。重复评估高敏肌钙蛋白T的血浆水平。实验者对治疗方案不知情。与安慰剂相比，褪黑激素未显著增加心肌挽救指数[褪黑激素21.8%（16.1; 24.8）vs.安慰剂20.2%（16.9; 27.0），p = 1.00]。两组之间的微血管阻塞程度相似[褪黑激素3.8%（2.7; 7.1）vs.安慰剂3.7%（1.3; 7.7），p = 0.96]。褪黑激素组高敏肌钙蛋白T释放的曲线下面积无显著性降低32%[褪黑激素AUC 12，343.9（6，889.2; 20，147.4）ng h/L vs.安慰剂AUC 18，285.3（5，180.4; 23，716.8）ng h/L，p = 0.82]。联合冠状动脉内和静脉注射褪黑激素并不能减轻心肌再灌注损伤。缺乏积极作用可能是由于褪黑激素的无效剂量，II型错误或给药时机。
Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia-reperfusion injury. Melatonin, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma levels of high-sensitive troponin T were assessed repeatedly. The experimenters were blinded with regard to treatment regimen. Melatonin did not significantly increase myocardial salvage index compared with placebo [melatonin 21.8 % (16.1; 24.8) vs. placebo 20.2 % (16.9; 27.0), p = 1.00]. The extent of microvascular obstruction was similar between the groups [melatonin 3.8 % (2.7; 7.1) vs. placebo 3.7 % (1.3; 7.7), p = 0.96]. The area under the curve for high-sensitive troponin T release was insignificantly reduced by 32 % in the melatonin group [AUC melatonin 12,343.9 (6,889.2; 20,147.4) ng h/L vs. AUC placebo 18,285.3 (5,180.4; 23,716.8) ng h/L, p = 0.82]. Combined intracoronary and intravenous treatment with melatonin did not reduce myocardial reperfusion injury. The lack of a positive effect could be due to an ineffective dose of melatonin, a type II error or the timing of administration.