SB211475, a metabolite of carvedilol, reduces infarct size after myocardial ischemic and reperfusion injury in rabbits

The aim of this study was to investigate the effect of SB 211475, a metabolite of carvedilol with weak alpha(1)-adrenoceptor antagonism and antioxidant effect, on myocardial reperfusion injury and infarct size in anesthetized rabbits. The rabbits were subjected to 60 min of regional myocardial ischemia and 180 min of reperfusion. SE 211475 was administered either as 0.3, 1.0 or 3.0 mg/kg and compared to vehicle and carvedilol (1 mg/kg) treated animals. The lowest dose of SE 211475 (0.3 mg/kg) did not reduce infarct size compared to vehicle, whereas SE 211475 1.0 or 3.0 mg/kg reduced infarct size significantly compared to vehicle (41.2 +/- 2.2% and 40.5 +/- 2.8% vs. 59.1 +/- 3.9%, p < 0.05). Carvedilol reduced infarct size significantly more than SE 211475 1.0 and 3.0 mg/kg (28.8 +/- 3.9% vs. 41.2 +/- 2.2% and 40.5 +/- 2.7%, p < 0.05). Carvedilol and SE 211475 1.0 and 3.0 mg/kg reduced myeloperoxidase activity to the same extent, indicative of reduced inflammation. Rate-pressure product did not differ between doses of SE 211475. In conclusion, SE 211475 in the two highest doses reduced infarct size by protecting from reperfusion injury, possibly by reduced neutrophil accumulation. The superior cardiac protective effect of Carvedilol over SE 211475 are most likely due to its adrenergic pharmacology including non-selective beta- and alpha(1)-adrenoceptor antagonism. (C) 1998 Elsevier Science B.V. All rights reserved.