Yoerger Danita M, Best Catherine A, McQuillan Brendan M, Supple Gregory E, Guererro J Luis, Cluette-Brown Joanne E, Hasaba Ali, Picard Michael H, Stone James R, Laposata Michael
Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Am J Pathol. 2006 May;168(5):1435-42. doi: 10.2353/ajpath.2006.050537.
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.
脂肪酸乙酯(FAEEs)是乙醇的非氧化代谢产物,与乙醇诱导的心脏损伤有关。为了评估心肌组织在体内产生FAEEs的情况,我们在猪身上采用了改良的乙醇消融程序。对7头猪的左前降支冠状动脉远端进行了60分钟的控制性乙醇输注;在输注前、输注期间和输注后对冠状窦和外周静脉进行系列采血,以测量冠状窦和外周循环中FAEEs的产生量和乙醇水平。在一只动物中,还对心肌内9个不同部位的FAEEs进行了定量分析。心脏在接触乙醇后5分钟内就产生了FAEEs,在冠状窦血液中检测到了非常高浓度的FAEEs。在心脏组织的不同区域检测到FAEEs的量存在显著差异。发现冠状窦FAEEs与乙醇浓度之间存在很强的相关性(r = 0.9241,P < 0.00001)。将乙醇注入左前降支冠状动脉后,心脏产生FAEEs的速度很快,冠状窦血液中的水平比摄入乙醇后外周血中的水平高4至10倍。这些数据表明,FAEEs可能是乙醇诱导的心脏毒性的介质。