Efficacy of MCI-186, a free-radical scavenger and antioxidant, for resuscitation of nonbeating donor hearts

Objective: Oxygen-derived free radicals are responsible in part for reperfusion injury in globally ischemic myocardium. In this study, the efficacy for resuscitation of nonbeating donor hearts of MCI-186, a free-radical scavenger and antioxidant, was investigated in a pig transplantation model. Methods: Cardiac arrest was induced by asphyxiation. After 30 minutes of global ischemia, the hearts were excised and immediately reperfused from the aortic root with normoxemic blood cardioplegia (Po₂ 100 mm Hg) for 20 minutes, followed by perfusion with hyperoxemic blood (Po₂ 300 mm Hg). MCI-186 (3 mg/kg) was administered into the aortic root for the first 30 minutes of reperfusion in the treated group (n = 6), and untreated hearts were used as a control group (n = 6). Transplantation was performed with the heart beating. Results: Posttransplantation recovery of cardiac output, end-systolic pressure-volume ratio, and first derivative of pressure of the left ventricle in the treated group were significantly better than those in the control group. The coronary sinus-aortic root difference in malondialdehyde levels remained low throughout reperfusion in the treated group but abruptly increased after initiation of oxygenated blood perfusion in the control group. The MCI-186-treated hearts showed low degree of edema and well-preserved ultrastructure with normal-appearing organelles, whereas the untreated hearts had marked swelling of mitochondria and scant glycogen granules. Conclusion: MCI-186 exerts a cardioprotective action at least partly by inhibition of lipid peroxidation. Antioxidant therapy at the initial reperfusion is essential to successful resuscitation of nonbeating hearts by continuous myocardial perfusion.