Journal article
Triiodothyronine Activates Lactate Oxidation Without Impairing Fatty Acid Oxidation and Improves Weaning From Extracorporeal Membrane Oxygenation
Circulation journal : official journal of the Japanese Circulation Society, Vol.78(12), pp.2867-2875
01/01/2014
DOI: 10.1253/circj.CJ-14-0821
PMCID: PMC5570456
PMID: 25421230
Abstract
Background: Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. It has previously been shown that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury.
Methods and Results: Nineteen immature piglets (9.1-15.3 kg) were separated into 3 groups with ECMO (6.5 h) and wean: normal circulation (Group-C); transient coronary occlusion (10 min) for ischemia-reperfusion (IR) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon (C-13)-labeled lactate, medium-chain and long-chain FAs, was infused as oxidative substrates. Substrate fractional contribution (FC) to the citric acid cycle was analyzed by 13C-nuclear magnetic resonance. ECMO depressed circulating T3 levels to 40% of the baseline at 4 h and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [adenosine triphosphate]/[adenosine diphosphate] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR.
Conclusions: T3 releases inhibition of lactate oxidation following IR injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning.
Details
- Title: Subtitle
- Triiodothyronine Activates Lactate Oxidation Without Impairing Fatty Acid Oxidation and Improves Weaning From Extracorporeal Membrane Oxygenation
- Creators
- Masaki Kajimoto - Seattle Childrens Res Inst, Ctr Dev Therapeut, Seattle, WA 98101 USADolena R. Ledee - Seattle Childrens Res Inst, Ctr Dev Therapeut, Seattle, WA 98101 USAChun Xu - Seattle Childrens Res Inst, Ctr Dev Therapeut, Seattle, WA 98101 USAHidemi Kajimoto - Seattle Childrens Res Inst, Ctr Dev Therapeut, Seattle, WA 98101 USANancy G. Isern - Environmental Molecular Sciences LaboratoryMichael A. Portman - Seattle Children's Hospital
- Resource Type
- Journal article
- Publication Details
- Circulation journal : official journal of the Japanese Circulation Society, Vol.78(12), pp.2867-2875
- DOI
- 10.1253/circj.CJ-14-0821
- PMID
- 25421230
- PMCID
- PMC5570456
- NLM abbreviation
- Circ J
- ISSN
- 1346-9843
- eISSN
- 1347-4820
- Publisher
- Japanese Circulation Soc
- Number of pages
- 9
- Grant note
- Department of Energy's Office of Biological and Environmental Research; United States Department of Energy (DOE) R01HL060666 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01HL60666 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 01/01/2014
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics
- Record Identifier
- 9984961029002771
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