title: Rapid fatty acid ethyl ester synthesis by porcine myocardium upon ethanol infusion into the left anterior descending coronary artery.
abstract: Fatty acid ethyl esters (FAEEs), nonoxidative metabolites of ethanol, have been implicated in ethanol-induced heart injury. To assess the in vivo production of FAEEs by myocardial tissue, we used a modified ethanol ablation procedure in pigs. A controlled 60-minute ethanol infusion was administered into the distal left anterior descending coronary artery in seven swine; serial blood sampling of the coronary sinus and peripheral vein before, during, and after infusion allowed measurement of FAEE production and ethanol levels in the coronary sinus and the peripheral circulation. In a single animal, FAEEs were also quantified from nine different sites within the myocardium. FAEEs were produced by the heart within 5 minutes of exposure to ethanol, with very high concentrations of FAEEs detected in coronary sinus blood. Significant variability in amounts of FAEEs was detected in different regions of the heart tissue. A strong correlation was found between coronary sinus FAEEs and ethanol concentration (r = 0.9241, P < 0.00001). FAEE production by the heart after delivery of ethanol into the left anterior descending coronary artery was rapid, reaching levels in the coronary sinus blood 4 to 10 times greater than that found in peripheral blood after ethanol intake. These data demonstrate that FAEEs may be mediators of ethanol-induced cardiotoxicity.
authors.affiliation: Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. mlaposata@partners.org
authors.forename: Danita M
authors.initials: DM
authors.lastname: Yoerger
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Best
authors.forename: Brendan M
authors.initials: BM
authors.lastname: McQuillan
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Supple
authors.forename: J Luis
authors.initials: JL
authors.lastname: Guererro
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Cluette-Brown
authors.forename: Ali
authors.initials: A
authors.lastname: Hasaba
authors.forename: Michael H
authors.initials: MH
authors.lastname: Picard
authors.forename: James R
authors.initials: JR
authors.lastname: Stone
authors.forename: Michael
authors.initials: M
authors.lastname: Laposata
mesh_terms: D000818:Animals; D017115:Catheter Ablation; D003331:Coronary Vessels / Q000502:physiology*; D004452:Echocardiography; D004951:Esterification; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics*; D005227:Fatty Acids / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D013552:Swine
chemical_list: D005227:Fatty Acids; D000431:Ethanol