Carvedilol improves function and reduces infarct size in the feline myocardium by protecting against lethal reperfusion injury

This study examined the effect of carvedilol, a vasodilating beta-adrenoceptor antagonist and antioxidant, on lethal reperfusion injury in feline hearts subjected to 40 min of regional ischaemia and 180 min of reperfusion. 30 open chest anaesthetized cats were randomized into three groups. A control group (n = 10) was compared with a group given carvedilol before coronary artery occlusion (n = 10) and a group given carvedilol immediately before and during early reperfusion (n = 10). Regional myocardial function was measured by sonomicrometry. Infarct size was determined by staining the left ventricle with triphenyl tetrazolium chloride. Myocardial blood flow was measured by radiolabeled microspheres. Tissue levels of glutathione were measured after reperfusion. Infarct size was significantly reduced compared to control both when carvedilol was given before ischaemia (0.2 +/- 0.1 vs. 17.6 +/- 3.6%, P < 0.05) and when given immediately before reperfusion (3.7 +/- 1.3 vs. 17.6 +/- 3.6%, P < 0.05). Regional shortening improved significantly and the incidence of ventricular fibrillation during early reperfusion was reduced in both groups treated with carvedilol compared to control. Oxidized glutathione did nor differ between groups in the post-ischaemic myocardium. This study supports that lethal reperfusion injury is a significant phenomenon. Furthermore, carvedilol reduces infarct size and reperfusion arrhythmias, and improves post-ischaemic regional myocardial function by protecting against both ischaemic and lethal reperfusion injury. The present study does not answer whether it is the non-selective beta- or alpha(1)-adrenoceptor antagonism the antarrhytmic or the antioxidant actions of carvedilol that is responsible for the protective effect.