Background Experimental evidence suggests that cyclosporine,which inhibits the opening of mitochondrial permeability-transitionpores, attenuates lethal myocardial injury that occurs at thetime of reperfusion. In this pilot trial, we sought to determinewhether the administration of cyclosporine at the time of percutaneouscoronary intervention (PCI) would limit the size of the infarctduring acute myocardial infarction.
Methods We randomly assigned 58 patients who presented withacute ST-elevation myocardial infarction to receive either anintravenous bolus of 2.5 mg of cyclosporine per kilogram ofbody weight (cyclosporine group) or normal saline (control group)immediately before undergoing PCI. Infarct size was assessedin all patients by measuring the release of creatine kinaseand troponin I and in a subgroup of 27 patients by performingmagnetic resonance imaging (MRI) on day 5 after infarction.
Results The cyclosporine and control groups were similar withrespect to ischemia time, the size of the area at risk, andthe ejection fraction before PCI. The release of creatine kinasewas significantly reduced in the cyclosporine group as comparedwith the control group (P=0.04). The release of troponin I wasnot significantly reduced (P=0.15). On day 5, the absolute massof the area of hyperenhancement (i.e., infarcted tissue) onMRI was significantly reduced in the cyclosporine group as comparedwith the control group, with a median of 37 g (interquartilerange, 21 to 51) versus 46 g (interquartile range, 20 to 65;P=0.04). No adverse effects of cyclosporine administration weredetected.
Conclusions In our small, pilot trial, administration of cyclosporineat the time of reperfusion was associated with a smaller infarctby some measures than that seen with placebo. These data arepreliminary and require confirmation in a larger clinical trial.
Source Information
From Hôpital Arnaud de Villeneuve, Montpellier (C.P., T.T.C., C.M., F.R., C.S., G.G.); Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon (P.C., P.S., H.T., G.R., N.M., E.B., D.A., G.F., X.A.-F., D.R., G.K., G.D., M.O.); Service de Cardiologie, Mulhouse (R.E., J.-P.M.); and INSERM Unité 886, Lyon (H.T., G.R., D.A., G.F., G.D., M.O.) — all in France.
Address reprint requests to Dr. Ovize at Hôpital L. Pradel, Hospices Civils de Lyon, 59, Blvd. Pinel, 69394 Lyon CEDEX 03, France, or at ovize{at}sante.univ-lyon1.fr.
Cyclosporine in Acute Myocardial Infarction
Theruvath T. P., Lemasters J. J., Rossi J. S., Simpson R. J. Jr., Hoffman I., Ibanez B., Badimon J. J., Ryding A. D., Piot C., Bonnefoy-Cudraz E., Ovize M.
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N Engl J Med 2008;
359:2286-2289, Nov 20, 2008.
Correspondence
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