Submitted on July 15, 2008
Revised on October 3, 2008
Accepted on October 6, 2008
Superior Cardiac Function Via Anaplerotic Pyruvate in the Immature Swine Heart After Cardiopulmonary Bypass and Reperfusion
Aaron K. Olson1, Outi M. Hyyti2, Gordon A. Cohen1, Xue-Han Ning3, Martin Sadilek2, Nancy Isern4, and Michael A. Portman1*
1 Children's Hospital and Regional Medical Center
2 University of Washington
3 Univ. of Washington
4 Pacific Northwest National Laboratory
* To whom correspondence should be addressed. E-mail: michael.portman{at}seattlechildrens.org.
Pyruvate produces inotropic responses in the adult reperfused heart. Pyruvate oxidation and anaplerotic entry into the citric acid cycle (CAC) via carboxylation are linked to 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 minutes starting either during weaning (Group I), after discontinuation (Group II) or without (Control) CPB. Hemodynamic data was collected. 13C NMR spectroscopy was used to determine the fraction of pyruvate entering the CAC via pyruvate carboxylation (PC) to total CAC 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 discontinuation of CPB did not. Glutamate fractional enrichment was confirmed by liquid chromatography mass spectroscopy as adequate to provide signal to noise in the NMR experiment in all groups. The ratio of PC to total pyruvate entry into the CAC cycle did not differ between groups (Group I 20±4%, Group II 23±7%, Control 27±7%). These data show that robust PC operates in the neonatal pig heart and is maintained during reperfusion under conditions which emulate cardiopulmonary bypass and reperfusion in human infants.
