Abstract 15633: Triiodothyronine Modifies Mitochondrial Substrate Utilization and Facilitates Weaning From Extracorporeal Membrane Oxygenation Following Cardiac Injury
Background: Extracorporeal membrane oxygenation (ECMO) provides a rescue for infants and children with severe cardiac failure occurring in clinical scenarios such as ischemia-reperfusion injury. Morbidity and mortality remain high often due to inability to wean. We previously showed that triiodothyronine supplementation (T3) improves cardiac function by modulating substrate metabolism. We hypothesized that T3 improves substrate utilization and citric acid cycle (CAC) flux, restores ventricular function, and facilitates weaning from ECMO after cardiac injury.
Methods: Fifteen immature piglets (9.1 -15.3 kg) were then separated into 3 groups: normal circulation (C); transient coronary occlusion (10 min) followed by ECMO (6.5 hours) and wean (IR); and IR with T3 supplementation (IR-T3) by bolus and infusion. We intracoronary infused 13-carbon (13C) labeled lactate, medium chain fatty acids and long chain fatty acids as oxidative substrate over the final hour. We used 13C nuclear magnetic resonance to determine substrate fractional contribution to the CAC (Fc).
Results: ECMO depressed circulating T3 levels to 35% baseline at 8 hours and were restored in IR-T3. IR injury severely decreased function reflected by cardiac power, which was not fully restorable in group IR, but was substantially improved (p <0.05) in IR-T3. IR also depressed Fc-lactate, while the superior contractile function in IR-T3 occurred along with a marked Fc-lactate increase without elevating myocardial oxygen consumption over C or IR.
Conclusions: T3 supplementation releases inhibition of pyruvate dehydrogenase flux following ischemia-reperfusion injury, and improves cardiac function without increasing ATP utilization. These findings indicate that T3 depression during ECMO is maladaptive and that restoring levels supports metabolic flux and contractile function thereby sustains weaning.
- © 2013 by American Heart Association, Inc.