Rationale: Triiodothyronine (T3) supplementation improves clinical outcomes in infants after cardiac surgery using cardiopulmonary bypass by unknown mechanisms. Objective: We utilized a translational model of infant cardiopulmonary bypass to test the hypothesis that T3 modulates pyruvate entry into the citric acid cycle (CAC) thereby providing the energy support for improved cardiac function after ischemia-reperfusion. Methods and Results: Neonatal piglets received intracoronary [2-13Carbon(13C)] pyruvate for 40 minutes (8 mM) during control aerobic conditions (Cont) or immediately after reperfusion (IR) from global hypothermic ischemia. A third group (IR-Tr) received T3 (1.2 ug/kg) during reperfusion. We assessed absolute CAC intermediate levels and flux parameters into the CAC through oxidative pyruvate decarboxylation (PDC) and anaplerotic carboxylation (PC) using [2-13C] pyruvate and isotopomer analysis by gas and liquid chromatography-mass spectrometry and 13C nuclear magnetic resonance spectroscopy. Compared to IR, T3 (group IR-Tr) increased cardiac power and oxygen consumption after ischemia-reperfusion while elevating flux of both PDC and PC (~ four-fold). While neither IR nor IR-Tr modified absolute CAC levels, T3 inhibited IR-induced reductions in their molar percent enrichment (MPE). Furthermore, 13C labeling of CAC intermediates suggest that T3 may decrease entry of unlabeled carbon at the level of oxaloacetate through anaplerosis or exchange reaction with asparate. Conclusions: T3 markedly enhances PC and PDC fluxes thereby providing potential substrate for elevated cardiac function after reperfusion. This T3-induced increase in pyruvate fluxes occur with preservation of the CAC intermediate pool. Our labeling data raise the possibility that T3 reduces reliance on amino acids for anaplerosis after reperfusion.
- cardiopulmonary bypass
- Copyright © 2011, American Journal of Physiology - Heart and Circulatory Physiology