Abstract 13561: Extracorporeal Membrane Oxygenation Promotes Long Chain Fatty Acid Metabolism in the Immature Swine Heart in vivo
Background: Extracorporeal membrane oxygenation (ECMO) unloads the heart and is frequently used in infants with postoperative cardiopulmonary failure, but the associated survival rate is still low. Nutritional manipulation may preserve or improve cardiac recovery, but little is known regarding the impact of ECMO on myocardial metabolism. Fatty acid (FA) oxidation is implicated in various models as a regulator of cardiac remodeling. We assessed the hypothesis that ECMO modulates free FA metabolism in the immature heart.
Methods and Results: Twenty two immature pigs (age 25-38 days) were divided into 4 groups by left ventricular (LV) loading status: Control (normal circulation) or ECMO (mechanically unloaded), and by delivery of [2-13C]lactate, [2,4,6,8-13C]octanoate (medium chain FA) and [U-13C]long chain FAs either directly into the coronary artery (high dose) or systemically (low dose; near physiological intracoronary concentration). LV tissue then underwent nuclear magnetic resonance (NMR) analysis for determination of the fractional contribution (Fc) of these substrates of acetyl-CoA to the citric acid cycle (CAC). ECMO lowered the LV end-diastolic pressure and myocardial oxygen consumption while maintaining cardiac output. ECMO with high dose infusion showed an about 2-fold greater long chain FAs Fc than observed in Control (7.4 ± 1.4 vs. 12.7 ± 1.8%; P < 0.05). ECMO also reduced the lactate Fc (9.7 ± 0.7 vs. 3.4 ± 0.3 %; P < 0.01), whereas medium chain FA oxidation was not altered by ECMO, providing more than 60% of CAC oxidation via acetyl-CoA. Low dose infusion study showed high Fc of endogenous substrates, but relatively same metabolic shift of exogenous substrates as high dose infusion study. Immunoblot analysis also demonstrated upregulation of pyruvate dehydrogenase kinase 4 in the ECMO group. Myocardial [NADH]/[NAD+] measured via 1H-NMR trended downward with ECMO but significantly increased with high-dose delivery.
Conclusions: ECMO reduces cardiac work and myocardial oxygen consumption, and shifts substrate preference towards long chain FAs. These findings suggest that manipulation of substrate utilization may be used therapeutically during ECMO to prevent adverse myocardial remodeling and enhance weaning.
- Extracorporeal circulation
- Cardiac metabolism
- Ventricular remodeling
- Magnetic resonance spectroscopy
- Congenital heart surgery
- © 2012 by American Heart Association, Inc.