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.

Figure 1

A: Mean (±SEM) coronary sinus FAEE concentration (pmol/ml) − time curve (n = 6) during and after ethanol infusion (g/kg). B: Mean (±SEM) coronary sinus ethanol concentration (mg/dl) − time curve during and after ethanol infusion (g/kg).

Figure 2

A: Mean (±SEM) peripheral vein FAEE concentrations (pmol/ml) − time curve (n = 6) during and after ethanol infusion (g/kg). B: Mean (±SEM) peripheral vein ethanol (mg/dl) − time curve during and after ethanol infusion (g/kg).

Figure 3

The correlation between blood ethanol and FAEEs in the coronary sinus of each pig.

Figure 4

The correlation between blood ethanol and FAEEs in the peripheral vein of each pig.

Figure 5

A: Superficial anatomy of the anterior view (sternocostal) of the heart and a detailed sectional view through the heart showing the areas assayed for FAEE analysis. B: Histogram of the FAEE levels (nmol/g tissue) taken from nine areas of the heart. C: FAEE distribution (% of total) in the nine assayed areas of the heart.