Effects of acute and chronic angiotensin receptor blockade on myocardial vascular blood volume and perfusion in a pig model of coronary microembolization

Based on the reduction of ischemic cardiac events in clinical trials and ex perimental observations, inhibition of the effects of angiotensin II on cor onary microcirculatory function may afford myocardial protection after inju ry. The immediate effects of intracoronary AT(1) receptor blockade with irb esartan were examined in a pig model in the healthy myocardium and in acute ischemia induced by injection of 30-mu m microspheres into the left anteri or descending coronary artery (LAD). Electron-beam computed tomography was performed for in-vivo quantitative measurements of regional intramyocardial vascular blood volume (V-B) and perfusion (F-M), as well as left ventricul ar ejection fraction (LVEF) and muscle mass, Ratios of V-B and F-M in the a nterior (LAD-supplied)/inferior (control) myocardium were generated. At bas eline, 0.2 mg/kg irbesartan injected into the LAD increased V-B and F-M rat ios significantly by 27 +/- 8% and 51 +/- 13%, respectively. After anterior coronary microembolization, V-B and F-M ratios were 0.60 +/- 0.05 and 0.51 +/- 0.05, respectively, and were significantly increased by irbesartan (by 24 +/- 10% and by 36 +/- 11%, respectively). After 4 weeks of treatment wi th oral irbesartan (n = 7) or placebo (n = 7), an improved LVEF (56 +/- 4% v 44 +/- 4%, P = .046) was observed in irbesartan-treated animals, but no d ifference in LV end-diastolic volumes or muscle mass. Resting V-B (0.95 +/- 0.06 v 0.76 +/- 0.06; P = .047) and F-M (0.84 +/- 0.05 v 0.64 +/- 0.04; P = .016) ratios were significantly greater in irbesartan-treated animals. Us ing adenosine, there was a trend for higher V-B and F-M ratios in irbesarta n-v placebo-treated animals. Therefore, in a pig model of acute myocardial ischemia, AT(1) receptor blockade by irbesartan induced microvascular vasod ilation and, ostensibly, conveyed myocardial protection. Long-term treatmen t with irbesartan resulted in moderate enhancements of resting V-B and F-M compared with placebo, suggesting a role for coronary microcirculatory effe cts of chronic AT, receptor blockade in preserving LVEF. (C) 2000 American Journal of Hypertension, Ltd.