Attenuation of myocardial stunning by the AT₁ receptor antagonist candesartan

Abstract

The effect of AT₁ receptor blockade on myocardial stunning is still somewhat ambiguous. In some prior studies, coronary occlusion was of too long duration such that the effects of infarction and stunning on the recovery of contractile function could not be distinguished. In others, blood pressure was decreased such that the improved wall excursion could be the consequence of reduced afterload and/or of attenuated stunning. The present study, therefore, investigated the effect of the AT₁ receptor antagonist candesartan in a pure model of myocardial stunning with controlled systemic hemodynamics. Fourteen anesthetized open-chest dogs were subjected to 15 minutes occlusion of the left circumflex coronary artery (LCx) and 4 hours subsequent reperfusion. Systemic hemodynamics (micromanometer), regional myocardial blood flow (colored microspheres), and posterior wall thickening (PWT, sonomicrometry) were measured, and data were compared between 7 placebo controls (group 1) and 7 dogs receiving 1 mg/kg candesartan i.v. before LCx occlusion (group 2). Left ventricular peak pressure was kept constant by an intra-aortic balloon, and heart rate did not change throughout the protocol. Regional myocardial blood flow was not different between the groups under control conditions, increased in response to candesartan in group 2 (posterior subendocardial blood flow from 0.99 ± 0.18 to 1.57 ± 0.45; p < 0.05 vs. control conditions), but was not different during myocardial ischemia and at 4 hours of reperfusion between the groups. Under control conditions and during myocardial ischemia, PWT was also not different between the groups. At 4 hours of reperfusion, PWT was still depressed in group 1 (−1.5 ± 3.4 % vs. 17.7 ± 5.6 % during control conditions, p < 0.05), whereas PWT had recovered in group 2 (11.4 ± 3.7 % at 4 hours reperfusion vs. 18.3 ± 2.7 during control conditions, NS, p < 0.05 vs. group 1). In conclusion, pretreatment with the AT₁ receptor antagonist candesartan improved the functional recovery of reperfused myocardium. This attenuation of myocardial stunning was not based on more favorable systemic hemodynamics or regional myocardial blood flow.