Effects of inhibition of fatty acid oxidation on myocardial kinetics of ¹¹C-labeled palmitate

The effects of glucose and lactate infusion on palmitate oxidation were compared with the effect of 2-tetradecylglycidic acid (TDGA), an irreversible inhibitor of the carnitine acyltransferase I, in normoxic canine myocardium. The initial capillary transit retention fraction of [1-¹¹C]palmitate and its fractional distribution between oxidation and esterification in myocardium were measured by the residue detection method after intracoronary tracer injection, as well as by effluent measurements of ¹²CO₂, the end product of palmitate oxidation. TDGA reduced the initial capillary transit retention fraction (From 56 ± 13% to 37 ± 6%; p < 0.001) and oxidation of palmitate (n = 19), as also evidenced by the decrease in the fraction of tracer released as ¹¹CO₂ from 28 ± 5% to 6 ± 3% (p < 0.001). Infusion of carbohydrate (glucose or lactate; n = 6) reduced ¹¹CO₂ production from 30 ± 7% to 7 ± 4% (p < 0.05) but did not alter the initial capillary transit retention fraction of tracer (59 ± 5% vs. 56 ± 10%; NS). The latter was due to increased esterification into neutral ipids (41 ± 11% of injected palmitate after carbohydrate infusion versus 21 ± 12% in control conditions), as measured from multiexponential curve fittings. When carbohydrates were given after inhibition of palmitate oxidation by TDGA (n = 7), the ¹¹C tissue clearance kinetics were strikingly similar to those observed after carbohydrate infusion alone. Thus, enhanced metabolic trapping of [1-¹¹C]palmitate in myocardium resulted in initial capillary transit retention fractions that were not different from control conditions (41 ± 5% vs. 48 ± 12%; NS) despite inhibition of oxidation. The results show that the intracellular metabolism of palmitate contributes to the control of its uptake by myocardium. The findings are consistent with inhibition of palmitate oxidation by carbohydrates occurring at the same site as TDGA.