PNNL

Abstract

Extracorporeal membrane oxygenation (ECMO) is frequently used in infants with postoperative cardiopulmonary failure. ECMO also suppresses circulating triiodothyronine (T3) levels and modifies myocardial metabolism. We assessed the hypothesis that T3 supplementation reverses ECMO induced metabolic abnormalities in the immature heart. Twenty-two male Yorkshire pigs (age 25-38 days) with ECMO were received [2-13C]lactate, [2,4,6,8-13C]octanoate (medium chain fatty acid) and [U-13C]long-chain fatty acids as metabolic tracers either systemically (totally physiological intracoronary concentration) or directly into the coronary artery (high substrate concentration) for the last 60 minutes of each protocol. Nuclear magnetic resonance (NMR) analysis of left ventricular tissue determined the fractional contribution (Fc) of these substrates to the citric acid cycle (CAC). Fifty percent of the pigs in each group received intravenous T3 supplement (bolus at 0.6 µg/kg and then continuous infusion at 0.2 µg/kg/hour) during ECMO. Under both substrate loading conditions T3 significantly increased lactate-Fc with a marginal increase in octanoate-Fc. Both T3 and high substrate provision increased myocardial energy status indexed by [Phosphocreatine]/[ATP]. In conclusion, T3 supplementation promoted lactate metabolism to the CAC during ECMO suggesting that T3 releases inhibition of pyruvate dehydrogenase. Manipulation of substrate utilization by T3 may be used therapeutically during ECMO to improve resting energy state and facilitate weaning.