• Masaki Kajimoto, Dolena R Ledee, Nancy G Isern, and Michael A Portman.
• Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington.
• Am. J. Physiol. Heart Circ. Physiol. 2017 Apr 1; 312 (4): H721-H727.

AbstractVenoarterial 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 (T3)] to alter substrate utilization. Carbon 13 (13C)-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 13C-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 T3 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 T3 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.Copyright © 2017 the American Physiological Society.

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