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

Axel Schmermund, Lilach O Lerman, John A. Rumberger, Patricia E. Lund, Eric A. Pfeifer, Patrick F. Sheedy, Erik L. Ritman

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)827-837
Number of pages11
JournalAmerican Journal of Hypertension
Volume13
Issue number7
DOIs
StatePublished - 2000

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irbesartan
Angiotensin Receptors
Blood Volume
Blood Vessels
Swine
Perfusion
Stroke Volume
Placebos
Myocardium
Muscles
X Ray Computed Tomography

Keywords

  • AT receptor blockade
  • Coronary microembolization
  • Irbesartan
  • Pig

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effects of acute and chronic angiotensin receptor blockade on myocardial vascular blood volume and perfusion in a pig model of coronary microembolization. / Schmermund, Axel; Lerman, Lilach O; Rumberger, John A.; Lund, Patricia E.; Pfeifer, Eric A.; Sheedy, Patrick F.; Ritman, Erik L.

In: American Journal of Hypertension, Vol. 13, No. 7, 2000, p. 827-837.

Research output: Contribution to journalArticle

Schmermund, Axel ; Lerman, Lilach O ; Rumberger, John A. ; Lund, Patricia E. ; Pfeifer, Eric A. ; Sheedy, Patrick F. ; Ritman, Erik L. / Effects of acute and chronic angiotensin receptor blockade on myocardial vascular blood volume and perfusion in a pig model of coronary microembolization. In: American Journal of Hypertension. 2000 ; Vol. 13, No. 7. pp. 827-837.
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abstract = "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.",
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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.

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.

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