Journal Article
Journal of the American Heart Association, vol. 3, iss. 2, 2014
Authors
Matthew D. Files, Masaki Kajimoto, Colleen M. O'Kelly Priddy, Dolena R. Ledee, Chun Xu, Christine Des Rosiers, Nancy Isern, Michael A. Portman
Abstract
Background
Extracorporeal membrane oxygenation (
ECMO
) provides a bridge to recovery after myocardial injury in infants and children, yet morbidity and mortality remain high. Weaning from the circuit requires adequate cardiac contractile function, which can be impaired by metabolic disturbances induced either by ischemia‐reperfusion and/or by
ECMO
. We tested the hypothesis that although
ECMO
partially ameliorates metabolic abnormalities induced by
ischemia‐reperfusion
, these abnormalities persist or recur with weaning. We also determined if thyroid hormone supplementation (triiodothyronine) during
ECMO
improves oxidative metabolism and cardiac function.
Methods and Results
Neonatal piglets underwent transient coronary ischemia to induce cardiac injury then were separated into 4 groups based on loading status. Piglets without coronary ischemia served as controls. We infused into the left coronary artery [2‐
13
C]pyruvate and [
13
C
6
,
15
N]
l
‐leucine to evaluate oxidative metabolism by gas chromatography‐mass spectroscopy and nuclear magnetic resonance methods.
ECMO
improved survival, increased oxidative substrate contribution through pyruvate dehydrogenase, reduced succinate and fumarate accumulation, and ameliorated
ATP
depletion induced by ischemia. The functional and metabolic benefit of
ECMO
was lost with weaning, yet triiodothyronine supplementation during ECMO restored function, increased relative
pyruvate dehydrogenase
flux, reduced succinate and fumarate, and preserved
ATP
stores.
Conclusions
Although
ECMO
provides metabolic rest by decreasing energy demand, metabolic impairments persist, and are exacerbated with weaning. Treating
ECMO
‐induced thyroid depression with triiodothyronine improves substrate flux, myocardial oxidative capacity and cardiac contractile function. This translational model suggests that metabolic targeting can improve weaning.
