TY - JOUR
T1 - Effects of acute and chronic angiotensin receptor blockade on myocardial vascular blood volume and perfusion in a pig model of coronary microembolization
AU - Schmermund, Axel
AU - Lerman, Lilach O.
AU - Rumberger, John A.
AU - Lund, Patricia E.
AU - Pfeifer, Eric A.
AU - Sheedy, Patrick F.
AU - Ritman, Erik L.
N1 - Funding Information:
This study was funded by a research grant from Bristol-Myers Squibb Co., Princeton, NJ. Bristol-Myers-Squibb also kindly provided irbesartan. Dr. Schmermund was supported by grants from the German Research Association (Deutsche Forschungsgemeinschaft, Schm 1233/1-1) and the Heart Center Essen Cardiovascular Research Society (Schm 97-1).
PY - 2000
Y1 - 2000
N2 - Based on the reduction of ischemic cardiac events in clinical trials and experimental observations, inhibition of the effects of angiotensin II on coronary microcirculatory function may afford myocardial protection after injury. The immediate effects of intracoronary AT1 receptor blockade with irbesartan were examined in a pig model in the healthy myocardium and in acute ischemia induced by injection of 30-μm microspheres into the left anterior 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 ventricular ejection fraction (LVEF) and muscle mass. Ratios of (V(B)) and (F(M)) in the anterior (LAD-supplied)/inferior (control) myocardium were generated. At baseline, 0.2 mg/kg irbesartan injected into the LAD increased V(B) and F(M) ratios 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 with 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 difference 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. Using adenosine, there was a trend for higher V(B) and F(M) ratios in irbesartan- v placebo-treated animals. Therefore, in a pig model of acute myocardial ischemia, AT1 receptor blockade by irbesartan induced microvascular vasodilation and, ostensibly, conveyed myocardial protection. Long-term treatment with irbesartan resulted in moderate enhancements of resting V(B) and F(M) compared with placebo, suggesting a role for coronary microcirculatory effects of chronic AT1 receptor blockade in preserving LVEF. (C) 2000 American Journal of Hypertension, Ltd.
AB - Based on the reduction of ischemic cardiac events in clinical trials and experimental observations, inhibition of the effects of angiotensin II on coronary microcirculatory function may afford myocardial protection after injury. The immediate effects of intracoronary AT1 receptor blockade with irbesartan were examined in a pig model in the healthy myocardium and in acute ischemia induced by injection of 30-μm microspheres into the left anterior 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 ventricular ejection fraction (LVEF) and muscle mass. Ratios of (V(B)) and (F(M)) in the anterior (LAD-supplied)/inferior (control) myocardium were generated. At baseline, 0.2 mg/kg irbesartan injected into the LAD increased V(B) and F(M) ratios 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 with 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 difference 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. Using adenosine, there was a trend for higher V(B) and F(M) ratios in irbesartan- v placebo-treated animals. Therefore, in a pig model of acute myocardial ischemia, AT1 receptor blockade by irbesartan induced microvascular vasodilation and, ostensibly, conveyed myocardial protection. Long-term treatment with irbesartan resulted in moderate enhancements of resting V(B) and F(M) compared with placebo, suggesting a role for coronary microcirculatory effects of chronic AT1 receptor blockade in preserving LVEF. (C) 2000 American Journal of Hypertension, Ltd.
KW - AT receptor blockade
KW - Coronary microembolization
KW - Irbesartan
KW - Pig
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U2 - 10.1016/S0895-7061(00)00266-1
DO - 10.1016/S0895-7061(00)00266-1
M3 - Article
C2 - 10933576
AN - SCOPUS:0033861788
SN - 0895-7061
VL - 13
SP - 827
EP - 837
JO - American journal of hypertension
JF - American journal of hypertension
IS - 7
ER -