Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction

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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.NEJM 359:473-481 July 31, 2008
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.