Abstract

Background: Extracorporeal membrane oxygenation (ECMO) is the most frequently used mechanical circulatory support in children with cardiopulmonary failure. Nutritional energy support as well as inotropic support is important to recover cardiac function during ECMO. Fatty acids (FAs) are major myocardial energy source for citric acid cycle (CAC). Medium-chain FAs (MCFAs) are easily uptaken into cell and mitochondria without membrane transporters. Our previous animal study suggested that MCFAs can potentially use for myocardial energy metabolism as the best accessible substrates during ECMO. Even-numbered MCFAs enter into CAC via acetyl-CoA, while odd-numbered MCFAs are anaplerotic for the CAC as propionyl-CoA in addition to acetyl-CoA. This study assessed whether odd- or even-numbered MCFAs product efficient energy during a short-term ECMO. Methods: Fifteen male Yorkshire pigs (26-45 days old) with 8-hour ECMO were received either normal saline, heptanoate (odd-numbered MCFA) or octanoate (even-numbered MCFA) at 2.3 μmol/kg body wt/min as MCFAs systemically during ECMO (n = 5 per group). The 13-Carbon ( 13 C) labeled substrates ([2- 13 C]lactate, [5,6,7- 13 C 3 ]heptanoate and [U- 13 C 6 ]leucine) as metabolic markers were infused into coronary artery for the final hour before left ventricular tissue extraction. Extracted left ventricular tissues were analyzed for the 13 C-labeled and absolute concentrations of metabolites by nuclear magnetic resonance and gas chromatography-mass spectrometry. Results: There were no adverse events in any groups during experiments. Octanoate produced markedly high citrate concentration, indicating the conjugation of CAC, and led to high [ATP]/[ADP] ratio compared with other groups (6.2 ± 0.6, 6.0 ± 0.6 and 7.8 ± 0.5 in normal saline, heptanoate and octanoate, P < 0.05). Octanoate strongly increased the CAC metabolism through anaplerotic pathway from propionyl-CoA, but not heptanoate. Lactate oxidation and protein synthesis ratio from leucine were not different among 3 groups. Conclusions: Even-numbered MCFAs was superior energy source for CAC than odd-numbered MCFAs in normal heart supported with ECMO. These results support that nutritional therapy with even-numbered MCFAs facilitates weaning from ECMO.

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