Abstract 1551: Pyruvate Promotes Anaplerosis And Preserves Cardiac Function After Cardiopulmonary Bypass And Aortic Cross-clamping In Immature Pigs
Pyruvate produces inotropic responses in reperfused heart. However, the mechanisms and link between substrate metabolism and cardiac function still require definition. Also pyruvate responses in developing myocardium with potential limitations in anaplerosis are not known. We tested the hypothesis that pyruvate during early reperfusion promotes anaplerosis in the immature heart. Pigs (10–18 days old) were subjected to cardiopulmonary bypass, cooling to 28°C, and aortic cross-clamp with cardioplegia for 60 minutes. In group A (n = 4) -13C-pyruvate (150mM-300mM) was delivered intracoronary over 30 minutes to (2 mM) initiated while still supported on pump, and similar dosing started later in group B (n =4) after full removal from CPB circuit. The ratio of pyruvate carboxylation (PC anaplerosis and forming oxaloacetate) to pyruvate decarboxylation (PD forming acetyl-CoA entering the citric acid cycle) was determined via 13Carbon magnetic resonance spectroscopy and 13C labeled glutamate ratio analyses from left ventricular extracts. 13C fractional enrichment of glutamate, (in equilibrium with CAC intermediate α-ketoglutarate and quantitatively assayed by LC-MS) was 20% for group A, but barely detectable for group B (< 2%). Group A PC/PD was 0.24 ± 0.035 compared to 0.15 for pig heart not subjected to ischemia (n = 3). Cardiac power and dp/dt were 110± 11 and 134% ± 15 baseline in A, and only 59± 11 and 56% ± 4 in group B. Myocardial efficiency (LVpower/MVO) was maintained at preischemic baseline in A, but decreased > 50% in B. These data show that early provision of pyruvate during reperfusion replenishes CAC intermediates through anaplerosis, maintains oxidative capacity and efficiency, and improves post-reperfusion cardiac function in the immature heart. Furthermore, the developing heart responds positively to appropriate intraoperative substrate manipulation and shows capacity for anaplerosis.