title: Ethanol promotes arteriogenesis and restores perfusion to chronically ischemic myocardium.
abstract: BACKGROUND
  Moderate alcohol consumption is known to be cardioprotective compared with either heavy drinking or complete abstinence. We assessed the hypothesis that ethanol supplementation would improve myocardial function in the setting of chronic ischemia.
  
  
  RESULTS
  Sixteen male Yorkshire swine underwent placement of an ameroid constrictor into the left circumflex artery to induce chronic myocardial ischemia. Postoperatively, animals were supplemented with either 90 mL of ethanol (EtOH) daily (50%/V, EtOH) or 80 g of sucrose of equal caloric value (SUC), serving as controls. Seven weeks after ameroid placement, arteriolar density (1.74 ± 0.210% versus 3.11 ± 0.368% area of arterioles per low-powered field in sucrose (SUC) versus EtOH; P=0.004), myocardial perfusion (ratio of blood flow to the at-risk myocardium compared with the normal ventricle during demand pacing was 0.585 ± 0.107 versus 1.08 ± 0.138 for SUC versus EtOH; P=0.014), and microvascular reactivity were significantly increased in ethanol-treated animals compared with controls in the at-risk myocardium. Analysis of vascular endothelial growth factor and NOTCH pathway signaling suggested proneovascular and proliferative activity in the ischemic area. 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 increased arteriolar density and significantly improved myocardial perfusion and endothelium-dependent vasorelaxation in chronically ischemic myocardium. These findings suggest that, at moderate doses, ethanol directly promotes vasculogenesis and improves microvascular function, resulting in significant improvements in myocardial perfusion in the setting of chronic ischemia.
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Warren Alpert Medical School, Brown University, Providence, RI (A.D.L., N.Y.E., Y.L., J.F., T.A.B., N.W.K., F.W.S.); and Cardiology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (R.J.L.).
authors.forename: Antonio D
authors.initials: AD
authors.lastname: Lassaletta
authors.forename: Nassrene Y
authors.initials: NY
authors.lastname: Elmadhun
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Burgess
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Karlson
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Laham
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015425:Myocardial Reperfusion / Q000379:methods*; D009206:Myocardium; D013552:Swine; D013556:Swine, Miniature
chemical_list: D000431:Ethanol
keywords: alcohol; angiogenesis; coronary disease; endothelium; ischemia ▪ microcirculation; myocardium
references.citation: Circulation. 2010 Mar 9;121(9):1104-12
references.pmid: 20176991
references.citation: Angiogenesis. 2012 Dec;15(4):609-22
references.pmid: 22869002
references.citation: Eur Heart J. 2004 Jul;25(13):1153-62
references.pmid: 15231374
references.citation: Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19308-13
references.pmid: 20966350
references.citation: Angiogenesis. 2013 Jan;16(1):29-44
references.pmid: 22945845
references.citation: Basic Res Cardiol. 2011 Nov;106(6):897-909
references.pmid: 21713563
references.citation: J Surg Res. 2012 Dec;178(2):586-92
references.pmid: 22748601
references.citation: Alcohol. 2012 Aug;46(5):441-54
references.pmid: 22560293
references.citation: Circulation. 2012 Sep 11;126(11 Suppl 1):S65-72
references.pmid: 22965995
references.citation: Cardiol Clin. 2003 Aug;21(3):449-57
references.pmid: 14621457
references.citation: Angiogenesis. 2013 Apr;16(2):343-51
references.pmid: 23108591
references.citation: J Am Coll Surg. 2012 Nov;215(5):681-9
references.pmid: 22867714
references.citation: Mol Cell Biol. 2011 May;31(10):2010-25
references.pmid: 21402774
references.citation: Eur Rev Med Pharmacol Sci. 2012 May;16(5):630-8
references.pmid: 22774404
references.citation: Peptides. 2012 Dec;38(2):457-62
references.pmid: 22985857
references.citation: Curr Atheroscler Rep. 2011 Dec;13(6):439-46
references.pmid: 21870059
references.citation: Alcohol Clin Exp Res. 2011 Oct;35(10):1737-8
references.pmid: 21651586
references.citation: Clin Cardiol. 1997 May;20(5):420-4
references.pmid: 9134271
references.citation: Ann Surg Oncol. 2012 Jul;19 Suppl 3:S464-74
references.pmid: 21822553
references.citation: Eur Heart J. 1992 Nov;13 Suppl E:40-6
references.pmid: 1478208
references.citation: Microcirculation. 2009 Feb;16(2):193-206
references.pmid: 19152178
references.citation: Circulation. 2013 Mar 5;127(9):1018-27
references.pmid: 23378298