Effects of CV-3611, a New Free Radical Scavenger, on Ischemic Heart Failure in Conscious Beagle Dogs

Abstract

The effects of CV-3611, a new free radical scavenger, on coronary circulation failure and infarct size after ischemia/reperfusion were studied in conscious beagle dogs. The dogs underwent occlusion of the left circumflex coronary artery for 60 min and then were reperfused for 14 days. The dogs were divided into three groups: a control group, a pre-treated group that received CV-3611 or α-tocopherol, and a post-treated group that received CV-3611. During occlusion, varying degrees of ventricular arrhythmia were noted; after reperfusion, the arrhythmia tended to become severe. CV-3611 at a daily dose of 10 mg/kg or 30 mg/kg and a-tocopherol at a daily dose of 60 mg/kg reduced the incidence of overall post-occlusion arrhythmia. Coronary blood flow in the control group was reduced to 20% of the preocclusion level at 7 days after reperfusion, whereas in the CV-3611 and α-tocopherol treated groups, the decreased coronary flow was remarkably suppressed. The infarct size for the CV-3611- and α-tocopherol-treated groups, measured at 14 days after reperfusion, was reduced by 70% when compared with the control group. Based on these observations, it is proposed that CV-3611 exerts its beneficial effects on ischemic tissue by protecting against oxygen free radical-mediated damage induced by ischemia/reperfusion.