Superior cardiac function via anaplerotic pyruvate in the immature swine heart after cardiopulmonary bypass and reperfusion.
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-(13)C]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.
Olson
Aaron K
AK
Department of Pediatrics, University of Washington, Children's Hospital and Regional Medical Center, MSW 4841, 4800 Sand Point Way NE, Seattle, WA 98105, USA.
Hyyti
Outi M
OM
Cohen
Gordon A
GA
Ning
Xue-Han
XH
Sadilek
Martin
M
Isern
Nancy
N
Portman
Michael A
MA
D000818:Animals; D000831:Animals, Newborn; D002247:Carbon Isotopes; D002315:Cardiopulmonary Bypass; D002853:Chromatography, Liquid; D002952:Citric Acid Cycle; D018698:Glutamic Acid / Q000378:metabolism; D006439:Hemodynamics; D007263:Infusions, Parenteral; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D011766:Pyruvate Carboxylase / Q000378:metabolism; D019289:Pyruvic Acid / Q000008:administration & dosage / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D013552:Swine
D002247:Carbon Isotopes; D018698:Glutamic Acid; D019289:Pyruvic Acid; D011766:Pyruvate Carboxylase