Effects of Angiotensin II Type 1 Receptor Antagonist (Candesartan) in Preventing Fatal Ventricular Arrhythmias in Dogs during Acute Myocardial Ischemia and Reperfusion

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Abstract
Fatal arrhythmias may be prevented by long-term oral administration of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 (AT 1 ) receptor antagonists. However, there have been no studies evaluating the electrophysiologic changes that occur with the acute administration of AT 1 receptor antagonists during acute myocardial ische mia and reperfusion. This study aimed to evaluate the ability of candesartan to prevent fatal arrhythmias during acute myocardial ische mia and reperfusion. The left anterior descending (LAD) coronary artery was ligated for 10 min and then reperfused for 10 min in 45 adult mongrel dogs. Candesartan (1 mg/kg) or saline was administered intravenously 10 min before ligation of the LAD coronary artery (candesartan group [n = 20] and control group [n = 25], respectively). Changes in ventricular effective refractory period (ERP) and intramyocardial conduction time (ICT) in the risk area were compared during LAD occlusion and reperfusion. Ischemia-induced shortening of ERP was inhibited in the candesartan group compared with the control. There was a 4.7 ± 5.8% increase in ERP in the candesartan group, compared with a 11.5 ± 6.3% shortening in the control group (p