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Cyclosporine protects the heart during aortic valve surgery.

Anesthesiology (2014-07-23)
Pascal Chiari, Denis Angoulvant, Nathan Mewton, Olivier Desebbe, Jean-François Obadia, Jacques Robin, Fadi Farhat, Olivier Jegaden, Olivier Bastien, Jean-Jacques Lehot, Michel Ovize
ABSTRACT

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. 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. 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). 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cyclosporin A, 97.0-101.5% (on dried basis)
Sigma-Aldrich
Cyclosporin A, from Tolypocladium inflatum, BioReagent, for molecular biology, ≥95%
Sigma-Aldrich
Cyclosporin A, from Tolypocladium inflatum, ≥95% (HPLC), solid
Supelco
Cyclosporin A, VETRANAL®, analytical standard
Supelco
Cyclosporine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
(±)-CPP, solid
Supelco
Cyclosporin A solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Ciclosporin, European Pharmacopoeia (EP) Reference Standard