ANGIOTENSIN-II TYPE-1 RECEPTOR BLOCKADE WITH CANDESARTAN PROTECTS THEPORCINE MYOCARDIUM FROM REPERFUSION-INDUCED INJURY

Angiotensin-converting enzyme (ACE) inhibitors reduce myocardial ische mia/reperfusion injury. It is unclear whether reduced formation of ang iotensin II or attenuated degradation of bradykinin is responsible-for the beneficial effects. We investigated the role of endogenous angiot ensin II in ischemia/reperfusion injury by studying the effects of the angiotensin II type 1 receptor antagonist candesartan on myocardial f unction, infarct size, and perfusion after ischemia/reperfusion. Anest hetized pigs were subjected to 45 min of regional ischemia and 240 min of reperfusion. Starting 5 min before reperfusion, four groups of pig s (n = 6 in each) received coronary venous retroinfusion of candesarta n (0.2, 2, or 20 mu g/kg) or vehicle for 30 min. Myocardial regional b lood flow was measured with radioactive microspheres in two separate g roups (n = 6 in each) given 20 mu g/kg candesartan or vehicle. Retroin fusion of 20 mu g/kg of candesartan improved recovery of left ventricu lar systolic segment shortening measured by sonomicrometry in the isch emic area compared with 0.2 mu g/kg of candesartan and vehicle. Infarc t size, as a percentage of the area at risk, was smaller in the 2 and 20 mu g/kg groups than in the vehicle group (39.1 +/- 11.6% and 34.8 /- 10.2% vs. 78.3 +/- 8.9%; p < 0.01). There was no difference between candesartan and vehicle in their effects on regional myocardial blood flow. Angiotensin II type 1 receptor blockade supports myocardial fun ctional recovery and reduces infarct size. This effect is not related to improved regional myocardial blood flow during reperfusion.