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-adre noceptor antagonist and antioxidant, on lethal reperfusion injury in f eline hearts subjected to 40 min of regional ischaemia and 180 min of reperfusion. 30 open chest anaesthetized cats were randomized into thr ee groups. A control group (n = 10) was compared with a group given ca rvedilol before coronary artery occlusion (n = 10) and a group given c arvedilol immediately before and during early reperfusion (n = 10). Re gional myocardial function was measured by sonomicrometry. Infarct siz e was determined by staining the left ventricle with triphenyl tetrazo lium chloride. Myocardial blood flow was measured by radiolabeled micr ospheres. 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 significant ly and the incidence of ventricular fibrillation during early reperfus ion was reduced in both groups treated with carvedilol compared to con trol. Oxidized glutathione did nor differ between groups in the post-i schaemic myocardium. This study supports that lethal reperfusion injur y is a significant phenomenon. Furthermore, carvedilol reduces infarct size and reperfusion arrhythmias, and improves post-ischaemic regiona l myocardial function by protecting against both ischaemic and lethal reperfusion injury. The present study does not answer whether it is th e non-selective beta- or alpha(1)-adrenoceptor antagonism the antarrhy tmic or the antioxidant actions of carvedilol that is responsible for the protective effect.