CARVEDILOL PROTECTS AGAINST LETHAL REPERFUSION INJURY THROUGH ANTIADRENERGIC MECHANISMS

We examined the effect of carvedilol as compared with that of a combin ation of propranolol and doxazosin on lethal reperfusion injury in 21 feline hearts subjected to 40-min regional ischemia and 180-min reperf usion. A control group (n = 7) was compared with one group given carve dilol, a nonselective beta- and alpha(1)-adrenoceptor blocker and anti oxidant (n = 7) and another group given nonselective beta- and alpha(2 )-adrenoceptor blockade with propranolol and doxazosin (n = 7) during initial reperfusion. Infarct size (IS: percent of area at risk, AAR) d etermined by staining the myocardium with triphenyl tetrazolium chlori de (TTC), was reduced both in the carvedilol-treated group (median 1.8 %, p < 0.05) and in the group given propranolol/doxazosin (median 6.5% , p < 0.05) as compared with controls (median 14.4%). Treatment with c arvedilol reduced IS more than did treatment with propranolol/doxazosi n (p < 0.05). Longitudinal segment shortening measured with sonomicrom etry, improved in both treatment groups as compared with control (p < 0.05), but to a greater extent in the group treated with carvedilol. I n circumferential segments, only carvedilol significantly improved seg ment shortening. The incidence of ventricular fibrillation (VF) after reperfusion was reduced in both treatment groups as compared with cont rol. Oxidized glutathione and thiobarbituric acid-reactive substances (TEARS) measured at the end of reperfusion did not differ between grou ps. Carvedilol protected against lethal reperfusion injury mainly thro ugh blockade of adrenoceptors.