Abstract 13104: L-carnitine Supplementation Improves Right Ventricular Function in Two Models of Right Ventricular Failure

Introduction: Previous studies have shown that right ventricular (RV) failure in pulmonary arterial hypertension is characterized by diminished fatty acid oxidation and ultimate lipotoxicity due to accumulation of toxic lipid intermediates. Whether or not augmenting fatty acid oxidation can reverse lipotoxic RV failure in PAH is not known. Hypothesis: In this study, we tested the hypothesis that augmentation of fatty acid oxidation through L-carnitine supplementation reverses RV failure in two models of RV failure. Methods: BMPR2 (R899X) mice were allowed to develop PAH for 10 weeks prior to supplementation of L-carnitine or control in their water for 8 weeks. In a second model, wild type C57/BL6 mice underwent pulmonary artery banding and were treated with L-carnitine or control 2 weeks after banding surgery. Finally, L-carnitine supplementation was also tested on H9C2 cardiomyocyte-like cells transfected with mutant BMPR2. Lipid accumulation was measured by Oil Red O or BODIPY stain. Fatty acid-mediated mitochondrial respiration was measured by Oroboros Oxygraph or Seahorse analysis. Results: In vivo , L-carnitine in BMPR2 mice and pulmonary artery banded mice increased RV cardiac output, RV ejection fraction, and mitochondrial respiration of long-chain fatty acids. Hemodynamic improvement in RV cardiac output was confirmed in pulmonary artery banded mice. In vitro , L-carnitine reduced lipid accumulation and increased fatty acid oxidation in BMPR2 mutant H9C2 cells through a Cpt1-dependent mechanism. Conclusions: In summary, augmentation of fatty acid oxidation in right ventricular failure through L-carnitine supplementation improves RV function, increases fatty acid oxidation, and decreases lipid accumulation.