Triiodothyronine Activates Lactate Oxidation Without Impairing Fatty Acid Oxidation and Improves Weaning From Extracorporeal Membrane Oxygenation

• Kajimoto Masaki

  Center for Developmental Therapeutics, Seattle Children’s Research Institute

• Ledee Dolena R.

  Center for Developmental Therapeutics, Seattle Children’s Research Institute

• Xu Chun

  Center for Developmental Therapeutics, Seattle Children’s Research Institute

• Kajimoto Hidemi

  Center for Developmental Therapeutics, Seattle Children’s Research Institute

• Isern Nancy G.

  Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory

• Portman Michael A.

  Center for Developmental Therapeutics, Seattle Children’s Research Institute Division of Cardiology, Department of Pediatrics, University of Washington

抄録

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 (¹³C)-labeled lactate, medium-chain and long-chain FAs, was infused as oxidative substrates. Substrate fractional contribution (FC) to the citric acid cycle was analyzed by¹³C-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. (Circ J 2014; 78: 2867–2875)

収録刊行物

• Circulation Journal

  Circulation Journal 78 (12), 2867-2875, 2014

  一般社団法人 日本循環器学会

キーワード

• ECMO
• Myocardial metabolism
• Pediatric

詳細情報

• CRID: 1390001205108798464
• NII論文ID: 130004701549
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-14-0821
• ISSN: 13474820
• ISSN: 13469843
• NDL書誌ID: 025928288
• PubMed: 25421230
• Web Site: http://id.ndl.go.jp/bib/025928288
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I025928288
• Web Site: https://www.jstage.jst.go.jp/article/circj/78/12/78_CJ-14-0821/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015278535
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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