Effects of 2-tetradecylglycidic acid on myocardial function in swine hearts

Fatty acids in excess impair myocardial function in intact hearts both during aerobic and ischemic blood flow. The purpose of these studies was to determine whether decreases in acylcarnitine, effected by 2-tetradecylglycidic acid (TDGA), would result in the preservation of myocardial function in intact hearts during fatty acid excess. Two groups of intact working swine hearts in which serum fatty acids were augmented three- to fourfold were perfused extracorporeally with whole blood and compared over 90 min. Labeled [U-14C]palmitate was administered selectively into the left anterior descending coronary circulation to follow fatty acid oxidation, and regional myocardial function was assessed with ultrasonic crystals. Coronary flow in this bed was decreased by 50% over the final 30 min of perfusion. Treated swine (n = 10) were compared with a placebo-treated control group (n = 9). At similar levels of aerobic flow, TDGA effected a marked decrease in 14CO2 production during 60 min of aerobic perfusion, but levels were similar during the final 30 min of ischemia. Tissue levels of acylcarnitine were significantly reduced and acetyl-CoA levels significantly increased in TDGA-treated hearts both in aerobic and ischemic myocardium. This inhibition of fatty acid metabolism during aerobic flow was associated with an increase in regional myocardial shortening in the treated group. This occurred at similar levels of O2 consumption, evidencing enhanced carbohydrate substrate utilization. During the first 30 min of ischemia 14CO2 production and mechanical function were compromised similarly, whereas lactate production was 70% less (P less than 0.025) in the treated group.(ABSTRACT TRUNCATED AT 250 WORDS)