title: Effects of continuous triiodothyronine infusion on the tricarboxylic acid cycle in the normal immature swine heart under extracorporeal membrane oxygenation in vivo.
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 received [2-(13)C]lactate, [2,4,6,8-(13)C4]octanoate (medium-chain fatty acid), and [U-(13)C]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 min of each protocol. NMR analysis of left ventricular tissue determined the fractional contribution of these substrates to the tricarboxylic acid cycle. 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(-1)·h(-1)) during ECMO. Under both substrate loading conditions, T3 significantly increased the fractional contribution of lactate with a marginal increase in the fractional contribution of octanoate. Both T3 and high substrate provision increased the myocardial energy status, as indexed by phosphocreatine concentration/ATP concentration. In conclusion, T3 supplementation promoted lactate metabolism to the tricarboxylic acid cycle during ECMO, suggesting that T3 releases the inhibition of pyruvate dehydrogenase. Manipulation of substrate utilization by T3 may be used therapeutically during ECMO to improve the resting energy state and facilitate weaning.
authors: Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington;
authors: Masaki
authors: M
authors: Kajimoto
authors: Colleen M O'Kelly
authors: CM
authors: Priddy
authors: Dolena R
authors: DR
authors: Ledee
authors: Chun
authors: C
authors: Xu
authors: Nancy
authors: N
authors: Isern
authors: Aaron K
authors: AK
authors: Olson
authors: Michael A
authors: MA
authors: Portman
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002210:Caprylates / Q000378:metabolism; D002247:Carbon Isotopes; D002952:Citric Acid Cycle / Q000187:drug effects* / Q000502:physiology*; D004734:Energy Metabolism; D015199:Extracorporeal Membrane Oxygenation; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000032:analysis; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D034421:Sus scrofa; D014284:Triiodothyronine / Q000008:administration & dosage* / Q000097:blood
chemical_list: D002210:Caprylates; D002247:Carbon Isotopes; D011768:Pyruvate Dehydrogenase Complex; D010725:Phosphocreatine; D014284:Triiodothyronine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; C031492:octanoic acid
keywords: cardiac metabolism; citric acid cycle; extracorporeal circulation; fatty acids; pediatrics; thyroid hormone