Attenuation of myocardial stunning by the AT(1) receptor antagonist candesartan

The effect of AT(1) receptor blockade on myocardial stunning is still somew hat ambiguous. In: some prior studies, coronary occlusion was of too long d uration 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 consequen ce of reduced afterload and/or of attenuated stunning. The present study, t herefore, investigated the effect of the AT(1) receptor antagonist candesar tan in a pure model of myocardial, stunning with controlled systemic hemody namics. Fourteen anesthetized open-chest dogs were subjected to 15 minutes occlusion of the left circumflex coronary artery (LCx) and 4 hours subseque nt reperfusion. Systemic hemodynamics (micromanometer), regional myocardial bloodflow (colored microspheres), and posterior wall thickening (PWT, sono micrometry) were measured, and data were compared between 7 placebo control s (group 1) and 7 dogs receiving 1 mg/kg candesartan i.v. before LCx occlus ion (group 2). Left ventricular peak pressure was kept constant by an intra -aortic balloon, and heart rate did not change throughout the protocol. Reg ional myocardial blood flow was not different between the groups under cont rol 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 ha d 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, pr etreatment with the AT(1) receptor antagonist candesartan improved the func tional recovery of reperfused myocardium. This attenuation of myocardial st unning was not based on more favorable systemic hemodynamics or regional my ocardial blood how.