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Am J Physiol Heart Circ Physiol. 2015 Jul 1;309(1):H137-46. doi: 10.1152/ajpheart.00011.2015. Epub 2015 Apr 24.

Pyruvate modifies metabolic flux and nutrient sensing during extracorporeal membrane oxygenation in an immature swine model.

Author information

1
Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington;
2
Department of Surgery, University of Washington, Seattle, Washington;
3
Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington; Division of Cardiology, Department of Pediatrics, University of Washington, Seattle, Washington.
4
Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington;
5
Department of Nutrition, Université de Montréal and Montréal Heart Institute, Montréal, Quebec, Canada;
6
Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington; Division of Cardiology, Department of Pediatrics, University of Washington, Seattle, Washington michael.portman@seattlechildrens.org.

Abstract

Extracorporeal membrane oxygenation (ECMO) provides mechanical circulatory support for infants and children with postoperative cardiopulmonary failure. Nutritional support is mandatory during ECMO although specific actions for substrates on the heart have not been delineated. Prior work shows that enhancing pyruvate oxidation promotes successful weaning from ECMO. Accordingly, we tested the hypothesis that prolonged systemic pyruvate supplementation activates pyruvate oxidation in an immature swine model in vivo. Twelve male mixed-breed Yorkshire piglets (age 30-49 days) received systemic infusion of either normal saline (group C) or pyruvate (group P) during the final 6 h of 8 h of ECMO. Over the final hour, piglets received [2-(13)C] pyruvate, as a reference substrate for oxidation, and [(13)C6]-l-leucine, as an indicator for amino acid oxidation and protein synthesis. A significant increase in lactate and pyruvate concentrations occurred, along with an increase in the absolute concentration of the citric acid cycle intermediates. An increase in anaplerotic flux through pyruvate carboxylation in group P occurred compared with no change in pyruvate oxidation. Additionally, pyruvate promoted an increase in the phosphorylation state of several nutrient-sensitive enzymes, like AMP-activated protein kinase and acetyl CoA carboxylase, suggesting activation for fatty acid oxidation. Pyruvate also promoted O-GlcNAcylation through the hexosamine biosynthetic pathway. In conclusion, although prolonged pyruvate supplementation did not alter pyruvate oxidation, it did elicit changes in nutrient- and energy-sensitive pathways. Therefore, the observed results support the further study of pyruvate and its downstream effect on cardiac function.

KEYWORDS:

extracorporeal membrane oxygenation; leucine; metabolism; pyruvate

PMID:
25910802
PMCID:
PMC4491517
DOI:
10.1152/ajpheart.00011.2015
[Indexed for MEDLINE]
Free PMC Article

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