Fatty acid kinetics in aerobic myocardium: characteristics of tracer carbon entry and washout and influence of metabolic demand.

Abstract

These studies evaluated the kinetics of tracer uptake and washout after step-function labeling with 14C-palmitate. Washout and uptake function curve analysis for total radioactivity (TR) was derived according to the expressions: TR = Fx integral of 0 infinity C(t) x dt and TR = Fx integral of 0 infinity (Css - C(t)) x dt, respectively, with Vc = TR/Ca, where F = coronary flow; Css = steady-state concentration; C(t) = concentration with respect to time; Ca = arterial concentration; and Vc = distribution volumes within the fatty acid pathway. The only radioactive metabolites in venous effluent were fatty acids and 14CO2. The estimated Vc of fatty acids was small (1.2-1.7 ml/g dry wt or 0.4-0.5 mumol/g dry wt) and compatible with labeled substrate trapped in the blood volume. The Vc of 14CO2 was much larger (11.4-15.8 ml/g dry wt or 3.6-4.2 mumol/g dry wt) and correlated with counts contained in the aqueous soluble and fatty acid fractions in tissue. The counts in tissue were distributed between the aqueous soluble fraction (40%), which was rapidly depleted during washout, and a lipid fraction (60%) (triacylglycerols and phospholipids), which was resistant to washout. Distributions in tissue radioactivity between the aqueous soluble and lipid fractions support the notion of a dual pathway in fatty acid oxidation, one arm of which passes through the resident pool of triacylglycerols, which has a long time constant. The presence of this pool may impart an error in estimating fatty acid oxidation by external labeling techniques.