PMID- 28159812 OWN - NLM STAT- MEDLINE DCOM- 20170728 LR - 20200930 IS - 1522-1539 (Electronic) IS - 0363-6135 (Print) IS - 0363-6135 (Linking) VI - 312 IP - 4 DP - 2017 Apr 1 TI - Right ventricular metabolism during venoarterial extracorporeal membrane oxygenation in immature swine heart in vivo. PG - H721-H727 LID - 10.1152/ajpheart.00835.2016 [doi] AB - Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides hemodynamic rescue for patients encountering right or left ventricular (RV or LV) decompensation, particularly after surgery for congenital heart defects. ECMO, supported metabolically by parenteral nutrition, provides reductions in myocardial work and energy demand and, therefore, enhances functional recovery. The RV must often assume systemic ventricular pressures and function on weaning from VA-ECMO. However the substrate utilization responses of the RV to VA-ECMO or stimulation are unknown. We determined RV and LV substrate utilization response to VA-ECMO in immature swine heart. Mixed-breed male Yorkshire pigs (33-49 days old) underwent normal pressure volume loading (control, n = 5) or were unloaded by VA-ECMO (ECMO, n = 10) for 8 h. Five pigs with ECMO received intravenous thyroid hormone [triiodothyronine (T(3))] to alter substrate utilization. Carbon 13 ((13)C)-labeled substrates (lactate and medium-chain and long-chain fatty acids) were systemically infused as metabolic tracers. Analyses by nuclear magnetic resonance showed that both ventricles have similar trends of fractional (13)C-labeled substrate contributions to the citric acid cycle under control conditions. VA-ECMO produced higher long-chain fatty acids and lower lactate contribution to the citric acid cycle via inhibition of pyruvate dehydrogenase, whereas T(3) promoted lactate metabolism in both ventricles. However, these metabolic shifts were smaller in RV, and RV fatty acid contributions showed minimal response to perturbations. Furthermore, VA-ECMO and T(3) also achieved high [phosphocreatine]/[ATP] and low [NADH]/[NAD(+)] in LV but not in RV. These data suggest that the RV shows decreased ability to modify substrate utilization and achieve improvements in energy supply/demand during VA-ECMO.NEW & NOTEWORTHY We showed that the right ventricle unloaded by venoarterial extracorporeal membrane oxygenation (VA-ECMO) has diminished capacity to alter substrate utilization compared with the left ventricle. This decrease in metabolic flexibility contributes to the inability to increase high-energy phosphate reserves during myocardial rest by VA-ECMO. CI - Copyright (c) 2017 the American Physiological Society. FAU - Kajimoto, Masaki AU - Kajimoto M AD - Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington. FAU - Ledee, Dolena R AU - Ledee DR AD - Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington. FAU - Isern, Nancy G AU - Isern NG AD - Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratories, Richland, Washington; and. FAU - Portman, Michael A AU - Portman MA AD - Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington; michael.portman@seattlechildrens.org. AD - Division of Cardiology, Department of Pediatrics, University of Washington, Seattle, Washington. LA - eng GR - K01 HL120886/HL/NHLBI NIH HHS/United States GR - R01 FD004362/FD/FDA HHS/United States PT - Journal Article DEP - 20170203 PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 RN - 0 (Fatty Acids) RN - 0 (Pyruvate Dehydrogenase Complex) RN - 020IUV4N33 (Phosphocreatine) RN - 06LU7C9H1V (Triiodothyronine) RN - 0U46U6E8UK (NAD) RN - 33X04XA5AT (Lactic Acid) RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - Adenosine Triphosphate/metabolism MH - Animals MH - Energy Metabolism/physiology MH - *Extracorporeal Membrane Oxygenation MH - Fatty Acids/metabolism MH - Heart/*physiology MH - Heart Ventricles/diagnostic imaging/*metabolism MH - Hemodynamics/physiology MH - Lactic Acid/metabolism MH - Magnetic Resonance Spectroscopy MH - Male MH - Myocardium/*metabolism MH - NAD/metabolism MH - Phosphocreatine/metabolism MH - Pyruvate Dehydrogenase Complex/metabolism MH - Swine MH - Triiodothyronine/pharmacology PMC - PMC5407156 OTO - NOTNLM OT - cardiac metabolism OT - extracorporeal circulation OT - pediatrics OT - thyroid hormone EDAT- 2017/02/06 06:00 MHDA- 2017/07/29 06:00 PMCR- 2018/04/01 CRDT- 2017/02/05 06:00 PHST- 2016/12/19 00:00 [received] PHST- 2017/01/17 00:00 [revised] PHST- 2017/01/29 00:00 [accepted] PHST- 2017/02/06 06:00 [pubmed] PHST- 2017/07/29 06:00 [medline] PHST- 2017/02/05 06:00 [entrez] PHST- 2018/04/01 00:00 [pmc-release] AID - ajpheart.00835.2016 [pii] AID - H-00835-2016 [pii] AID - 10.1152/ajpheart.00835.2016 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2017 Apr 1;312(4):H721-H727. doi: 10.1152/ajpheart.00835.2016. Epub 2017 Feb 3.