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【NEJM】环孢素A对急性心肌梗死再灌注损伤的作用
Christophe Piot, M.D., Ph.D., Pierre Croisille, M.D., Patrick Staat, M.D., Hélène Thibault, M.D., Gilles Rioufol, M.D., Ph.D., Nathan Mewton, M.D., Rachid Elbelghiti, M.D., Thien Tri Cung, M.D., Eric Bonnefoy, M.D., Ph.D., Denis Angoulvant, M.D., Christophe Macia, M.D., Franck Raczka, M.D., Catherine Sportouch, M.D., Gerald Gahide, M.D., Gérard Finet, M.D., Ph.D., Xavier André-Fouët, M.D., Didier Revel, M.D., Ph.D., Gilbert Kirkorian, M.D., Ph.D., Jean-Pierre Monassier, M.D., Geneviève Derumeaux, M.D., Ph.D., and Michel Ovize, M.D., Ph.D.
ABSTRACT
Background Experimental evidence suggests that cyclosporine, which inhibits the opening of mitochondrial permeability-transition pores, attenuates lethal myocardial injury that occurs at the time of reperfusion. In this pilot trial, we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct during acute myocardial infarction.
Methods We randomly assigned 58 patients who presented with acute ST-elevation myocardial infarction to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight (cyclosporine group) or normal saline (control group) immediately before undergoing PCI. Infarct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging (MRI) on day 5 after infarction.
Results The cyclosporine and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before PCI. The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group (P=0.04). The release of troponin I was not significantly reduced (P=0.15). On day 5, the absolute mass of the area of hyperenhancement (i.e., infarcted tissue) on MRI was significantly reduced in the cyclosporine group as compared with the control group, with a median of 37 g (interquartile range, 21 to 51) versus 46 g (interquartile range, 20 to 65; P=0.04). No adverse effects of cyclosporine administration were detected.
Conclusions In our small, pilot trial, administration of cyclosporine at the time of reperfusion was associated with a smaller infarct by some measures than that seen with placebo. These data are preliminary and require confirmation in a larger clinical trial.
Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction
环孢素A对急性心肌梗死再灌注损伤的作用
ABSTRACT
摘要
Background Experimental evidence suggests that cyclosporine, which inhibits the opening of mitochondrial permeability-transition pores, attenuates lethal myocardial injury that occurs at the time of reperfusion. In this pilot trial, we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct during acute myocardial infarction.
背景：实验研究显示环孢素A，通过抑制线粒体通透性转运孔的开放，减轻再灌注时的致死性心肌损伤。在这项先导研究中，我们试图明确在经皮冠状动脉介入（PCI）时应用环孢素A是否能够限制急性心肌梗死梗死的梗死面积。
Methods We randomly assigned 58 patients who presented with acute ST-elevation myocardial infarction to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight (cyclosporine group) or normal saline (control group) immediately before undergoing PCI. Infarct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging (MRI) on day 5 after infarction.
方法：58例患急性ST段抬高性心肌梗死患者，随机分配在PCI前即刻时接受2.5mg/公斤体重的环孢素A（环孢素A组）或生理盐水（对照组）。所有患者的梗死面积通过检测肌酸激酶和肌钙蛋白I的释放来评估；在27例患者的亚组中，在心肌梗死后第5天接受磁共振显像（MRI）检查。
Results The cyclosporine and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before PCI. The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group (P=0.04). The release of troponin I was not significantly reduced (P=0.15). On day 5, the absolute mass of the area of hyperenhancement (i.e., infarcted tissue) on MRI was significantly reduced in the cyclosporine group as compared with the control group, with a median of 37 g (interquartile range, 21 to 51) versus 46 g (interquartile range, 20 to 65; P=0.04). No adverse effects of cyclosporine administration were detected.
结果：环孢素A组和对照组在PCI前的缺血事件、危险区面积和射血分数均相似。环孢素A组与对照组相比肌酸激酶的释放显著减少（P=0.04）。肌钙蛋白I的释放没有显著减少（P=0.15）。在第5天，环孢素A组磁共振显像的高强化区域绝对重量（即，梗死面积）与对照组相比显著减少，中位数37g（四分位区间，21-51）比 46g（四分位区间，20-65；P=0.04）。没有发现，环孢素A治疗的不良反应。
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作者:admin@医学,生命科学 2011-05-28 05:14
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