Triidothyronine and epinephrine rapidly modify myocardial substrate selection: a C-13 isotopomer analysis

Triiodothyronine (T-3) exerts direct action on myocardial oxygen consumptio n (M(V) over dot O-2), although its immediate effects on substrate metaboli sm have not been elucidated. The hypothesis, that T-3 regulates substrate s election and flux, was tested in isovolumic rat hearts under four condition s: control, T-3 (10 nM), epinephrine (Epi), and T-3 and Epi (TE). Hearts we re perfused with [1,3-C-13]acetoacetic acid (AA, 0.17 mM), L-[3-C-13] lacti c acid (LAC, 1.2 mM), U-C-13-labeled long-chain free fatty acids (FFA, 0.35 mM), and unlabeled D-glucose (5.5 mM) for 30 min. Fractional acetyl-CoA co ntribution to the tricarboxylic acid cycle (Fc) per substrate was determine d using C-13 NMR and isotopomer analysis. Oxidative fluxes were calculated using Fc, the respiratory quotient, and M(V) over dot O-2. T-3 increased (P < 0.05) Fc(FFA), decreased Fc(LAC), and increased absolute FFA oxidation f rom 0.58 +/- 0.03 to 0.68 +/- 0.03 <mu>mol.min(-1).g dry wt(-1) (P < 0.05). Epi decreased Fc(FFA) and Fc(AA), although FFA flux increased from 0.58 +/ - 0.03 to 0.75 +/- 0.09 <mu>mol.min(-1).g dry wt(-1).T-3 moderated the chan ge in Fc(FFA) induced by Epi. In summary, T-3 exerts direct action on subst rate pathways and enhances FFA selection and oxidation, although the Epi ef fect dominates at a high work state.