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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/H2315    most recent 00739.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Olson, A. K. Articles by Portman, M. A. Search for Related Content PubMed PubMed Citation Articles by Olson, A. K. Articles by Portman, M. A.

Superior cardiac function via anaplerotic pyruvate in the immature swine heart after cardiopulmonary bypass and reperfusion

¹Division of Cardiology, Department of Pediatrics, ²Department of Radiology, ³Division of Pediatric Cardiovascular Surgery, Department of Surgery, and ⁴Department of Chemistry, University of Washington, Seattle; ⁵Children's Hospital and Regional Medical Center, Seattle; and ⁶Pacific Northwest National Laboratory, Richland, Washington

Submitted 15 July 2008 ; accepted in final form 6 October 2008

Pyruvate produces inotropic responses in the adult reperfused heart. Pyruvate oxidation and anaplerotic entry into the tricarboxylic acid (TCA) cycle via carboxylation are linked to the stimulation of contractile function. The goals of this study were to determine if these metabolic pathways operate and are maintained in the developing myocardium after reperfusion. Immature male swine (age: 10–18 days) were subjected to cardiopulmonary bypass (CPB). Intracoronary infusion of [2-¹³C]pyruvate (to achieve an estimated final concentration of 8 mM) was given for 35 min, starting either during weaning (group I) and after its discontinuation (group II) or without (control) CPB. Hemodynamic data were collected. ¹³C NMR spectroscopy was used to determine the fraction of pyruvate entering the TCA cycle via pyruvate carboxylation (PC) to total TCA cycle entry (PC plus decarboxlyation via pyruvate dehydrogenase). Liquid chromatography-mass spectrometry was used to determine total glutamate enrichment. Pyruvate infusion starting during the weaning of mechanical circulatory support improved maximum dP/dt (P < 0.05) but waiting to start the infusion until after the discontinuation of CPB did not. Glutamate fractional enrichment was confirmed by liquid chromatography-mass spectroscopy as adequate (>5%) to provide signal to noise in the NMR experiment in all groups. The ratio of pyruvate carboxylase to total pyruvate entry into the TCA cycle did not differ between groups (group I: 20 ± 4%, group II: 23 ± 7%, and control: 27 ± 7%). These data show that robust PC operates in the neonatal pig heart and is maintained during reperfusion under conditions that emulate CPB and reperfusion in human infants.

cardiac metabolism; pyruvate carboxylation; pyruvate decarboxlyation; citric acid cycle; tricarboxylic acid cycle