Abstract 16793: Ethanol Promotes Arteriogenesis and Restores Perfusion to Chronically Ischemic Myocardium
Introduction: Moderate alcohol consumption is known to be cardioprotective as compared to either heavy drinking or complete abstinence. Proposed mechanisms include a generalized decrease in inflammation and oxidation as well as more specific cardiac effects. We assessed the hypothesis that ethanol supplementation would improve myocardial function in the setting of chronic ischemia.
Methods: Fourteen male Yorkshire swine underwent placement of an ameroid constrictor to the left circumflex artery to induce chronic myocardial ischemia. Post-operatively animals were supplemented with either 90 ml of ethanol daily (50%/V, EtOH, n = 7) or with 80 g of sucrose of equal caloric value (SUC, n = 7) serving as controls. Seven weeks after ameroid placement animals were evaluated for myocardial perfusion by neutron activation of injected microspheres at rest and during demand pacing. The ischemic myocardium was assessed by Western blot for protein expression and by immunofluorescence for vessel density.
Results: Arteriolar density was significantly increased in the ethanol-treated animals compared to controls as was myocardial perfusion during demand pacing as assessed by the ratio of blood flow between the ischemic area and the normal, remote ventricle. Expression of VEGF receptors 2 and 3, and the pro-inflammatory cytokine IL-8 was decreased in the ethanol-treated animals, while expression of the pro-proliferative TGF-β was increased. The average peak blood alcohol level in the treatment group was 40 ± 4 mg/dL consistent with levels of moderate drinking in humans.
Conclusions: Ethanol supplementation improved myocardial perfusion and increased microvessel density. The decreased expression of VEGF receptors 2 and 3 in the ischemic area is consistent with endocytotic internalization of activated VEGF receptors seen during angiogenesis, suggesting that ethanol may directly promote vasculogenesis in addition to its generalized anti-inflammatory properties.
- Ischemic heart disease
- Cardiovascular therapeutics
- Myocardial perfusion
- Coronary microcirculation
- © 2012 by American Heart Association, Inc.