Gamma-irradiated ceruloplasmin affords antifibrillatory protection against ischemia/reperfusion damage in the isolated rat heart

PURPOSE: Ceruloplasmin (CP), an important serum antioxidant, was previously found to reduce the incidence of ventricular fibrillation (VF) induced by ischemia and reperfusion in isolated rat hearts. The present study investigated whether CP sterilized by gamma-irradiation maintains its antiarrhythmic capacity and in vitro antioxidant properties. MATERIALS AND METHODS: Isolated rat hearts submitted to regional ischemia (15 min), were reperfused (10 min) with native CP or with CP irradiated at various doses (1-3 kGy) in the absence or presence of tyrosine (Tyr). RESULTS: All untreated hearts showed VF at reperfusion, which were all irreversible ventricular fibrillation (IVF). No IVF were found in hearts treated with native CP or gamma-irradiated CP. Cardioprotection afforded by irradiated CP (with or without Tyr) was slightly higher than that obtained with native CP. No VF at all (100% prevention) was found in hearts treated with CP irradiated alone or in the presence of tyrosine at 3 kGy. Tyrosine and irradiated tyrosine had no cardiotoxic or protective effects on reperfusion-induced arrhythmias. The Oxygen Radical Absorbing Capacity (ORAC), measured in vitro with beta-phycoerythrin (beta-PE) fluorescent indicator, was slightly higher for gamma-irradiated CP in the presence of Tyr. CONCLUSIONS: Ceruloplasmin sterilized by gamma-irradiation maintains antioxidant and antiarrhythmic effects in the post-ischemia reperfused isolated rat heart.