Abstract 15107: The Immature Right Ventricle Has Impaired Fatty Acid Metabolic Flexibility During Acute Physiologic Stressors
Introduction: To preserve the high energy phosphate reserves needed to maintain contractile function, myocardial substrate metabolism must adapt to acute stressors. Acute right ventricular (RV) failure frequently occurs postoperatively in infants and children due to pressure-overload from pulmonary arterial (PA) hypertension or RV outflow tract obstruction. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can be necessary to support the failing RV postoperatively. Unlike the left ventricle (LV), little is known about the metabolic response of the RV to acute stressors or VA-ECMO.
Hypothesis: The immature RV has a reduced ATP supply/demand ratio during acute pressure-overload due to impaired metabolic substrate flexibility, and secondly, the metabolic response to VA-ECMO differs between the RV and the LV.
Methods: Infant male Yorkshire piglets (12.6 ± 0.3 kg, n = 22) were utilized throughout. Firstly, PA banding for 2 hours (RV pressure-overload) versus sham was evaluated. The PA band was tightened to increase RV systolic pressure 2-fold above baseline. Separately, RV and LV were compared in piglets supported by VA-ECMO or sham for 8 hours. In all experiments, 13-carbon-labeled lactate, medium-chain fatty acid (FA) and mixed long-chain FAs were infused as oxidative substrates for the citric acid cycle for the final 1 hour, and then the myocardium was extracted for NMR analysis.
Results: PA banding diminished fractional contributions of FAs to the citric acid cycle (medium-chain FA; 14.5 ± 1.6 vs. 8.2 ± 1.0 %, long-chain FAs; 9.3 ± 1.5 vs. 5.1 ± 1.1 %, sham vs. PA banding respectively) and lowered phosphorylation potential (Phosphocreatine / ATP) by ~81%. VA-ECMO increased long-chain FAs and lowered lactate fractional contribution to citric acid cycle in the both the RV and LV, however, these changes were less pronounced in the RV.
Conclusions: Acute RV pressure-overload diminished phosphorylation potential, potentially related to decreased FAs utilization. Further, the RV did not increase FA utilization to a similar extent as the LV during VA-ECMO. In total, these results suggest that the immature RV has impaired flexibility with FA metabolism, and that strategies to promote FA oxidation should be targeted to improve RV function.
Author Disclosures: M. Kajimoto: None. N. Muhammad: None. N.G. Isern: None. C. Des Rosiers: None. A.K. Olson: None. M.A. Portman: None.
- © 2016 by American Heart Association, Inc.