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. 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. 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. 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.
