Myocardial metabolic changes in experimental non-hypertrophied and hypertrophied right ventricular failure

Metabolic shift toward glycolysis has been implicated in the development of RV dysfunction. We recently reported on experimental models of acute and chronic RV failure both related to RV activation of apoptosis and inflammation, but with variable RV hypertrophy. We sought to evaluate and compare the expressions of genes implicated in energy substrate use in these models of non-hypertrophied and hypertrophied RV failure. RV failure was induced by 1) a transient (90-min) pulmonary artery ensnarement in dogs, or by 2) a prolonged (six-month) overcirculation-induced pulmonary arterial hypertension in piglets. Hemodynamics was finally evaluated and RV free wall was sampled for pathobiological evaluation. In both models, RV presented with decreased expressions of α1, 2-subunits AMP-activated protein kinase, a key cellular energy sensor. Expressions of enzymes implicated in fatty acid oxidation, including carnitine palmitoyltransferase(CPT)-1A and -1B and sterol regulatory element binding transcription factor(SREBF)-1 and -2 decreased in the RV. This was associated with decreased RV expressions of genes implicated in fatty acid oxidation regulation, the peroxisome proliferator-activated receptor(PPAR)-α/PPAR-γ coactivator (PGC)-1 α in the RV. However, expressions of enzymes implicated in glycolytic pathways, including glucose transporter (GLUT1) and glucose-phosphorylating hexokinase-1, increased in hypertrophied dysfunctional RV, while they did not change in non-hypertrophied one. Acute and chronic afterload-induced RV failure is associated with altered RV fatty acid metabolism, while molecules implicated in glucose uptake are upregulated in the hypertrophied failing RV only.