Pascal Chiari1, Denis Angoulvant, Nathan Mewton, Olivier Desebbe, Jean-François Obadia, Jacques Robin, Fadi Farhat, Olivier Jegaden, Olivier Bastien, Jean-Jacques Lehot, Michel Ovize. 1. From the Department of Anesthesiology and Critical Care (P.C., O.D., O.B., J.-J.L.), Clinical Investigation Center (N.M., M.O.), Department of Cardiology (N.M., M.O.), and Department of Cardiothoracic Surgery (J.-F.O., J.R., F.F., O.J.), Centre Hospitalier Universitaire Louis Pradel, Lyon, France; Lyon University, Inserm U1060, CarMeN Laboratory, Univ Lyon-1, Lyon, France (P.C., N.M., J.-F.O., O.J., M.O.); and Department of Cardiology, Centre Hospitalier Universitaire de Tours and EA 4245 François Rabelais University, Tours, France (D.A.).
Abstract
BACKGROUND: Part of the myocardial damage occurring during cardiac surgery is a consequence of reperfusion injury. Cyclosporine, a potent inhibitor of the opening of the mitochondrial permeability transition pore, attenuates reperfusion injury in patients with acute ST-segment elevation myocardial infarction. This study investigated whether the administration of cyclosporine just before the aortic cross-unclamping would reduce myocardial injury in patients undergoing aortic valve surgery. METHODS: This study was a monocentric, prospective, randomized, single-blinded, controlled trial. Sixty-one patients, scheduled for elective aortic valve surgery, were randomly assigned (computer-generated randomization sequence) to receive either an intravenous bolus of cyclosporine (2.5 mg/kg, cyclosporine group, n = 30) or normal saline (control group, n = 31) 10 min before aortic cross-unclamping. The primary endpoint was the 72-h area under the curve for cardiac troponin I. RESULTS: Both groups were similar with respect to baseline characteristics and aortic cross-clamping duration. A significant 35% reduction of area under the curve for cardiac troponin I was observed in the cyclosporine group compared with the control group (242 ± 225 vs. 155 ± 71 arbitrary units, mean ± SD; mean difference, -86.2 ± 42.5; 95% CI, -172.3 to -0.1; P = 0.03). Cyclosporine beneficial effect remained significant after adjustment for aortic cross-clamping duration in each group (mean difference, -88 ± 34, 95% CI, -157 to -19; P = 0.01). None of the treated patients had significant side effects (odds ratio, 0.64; 95% CI, 0.16 to 2.55; P = 0.52). CONCLUSIONS:Cyclosporine administration at the time of reperfusion protects against reperfusion injury in patients undergoing aortic valve surgery. The clinical benefit of this protection requires confirmation in a larger clinical trial.
RCT Entities:
BACKGROUND: Part of the myocardial damage occurring during cardiac surgery is a consequence of reperfusion injury. Cyclosporine, a potent inhibitor of the opening of the mitochondrial permeability transition pore, attenuates reperfusion injury in patients with acute ST-segment elevation myocardial infarction. This study investigated whether the administration of cyclosporine just before the aortic cross-unclamping would reduce myocardial injury in patients undergoing aortic valve surgery. METHODS: This study was a monocentric, prospective, randomized, single-blinded, controlled trial. Sixty-one patients, scheduled for elective aortic valve surgery, were randomly assigned (computer-generated randomization sequence) to receive either an intravenous bolus of cyclosporine (2.5 mg/kg, cyclosporine group, n = 30) or normal saline (control group, n = 31) 10 min before aortic cross-unclamping. The primary endpoint was the 72-h area under the curve for cardiac troponin I. RESULTS: Both groups were similar with respect to baseline characteristics and aortic cross-clamping duration. A significant 35% reduction of area under the curve for cardiac troponin I was observed in the cyclosporine group compared with the control group (242 ± 225 vs. 155 ± 71 arbitrary units, mean ± SD; mean difference, -86.2 ± 42.5; 95% CI, -172.3 to -0.1; P = 0.03). Cyclosporine beneficial effect remained significant after adjustment for aortic cross-clamping duration in each group (mean difference, -88 ± 34, 95% CI, -157 to -19; P = 0.01). None of the treated patients had significant side effects (odds ratio, 0.64; 95% CI, 0.16 to 2.55; P = 0.52). CONCLUSIONS:Cyclosporine administration at the time of reperfusion protects against reperfusion injury in patients undergoing aortic valve surgery. The clinical benefit of this protection requires confirmation in a larger clinical trial.
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