TY - JOUR T1 - Adrenergic receptor blocker reverses cardiac metabolic remodeling and improves right ventricular function in experimental pulmonary hypertension JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p4757 AU - Jose Gomez-Arroyo AU - Shiro Mizuno AU - Laszlo Farkas AU - Donatas Kraskauskas AU - Daniela Farkas AU - Ayser Husseini AU - Antonio Abbate AU - Herman Bogaard AU - Norbert Voelkel Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p4757.abstract N2 - Albeit right ventricular failure (RVF) is a major complication in patients with pulmonary arterial hypertension, the knowledge on the pathobiology of RVF is still incomplete and RV-targeted therapies are practically non-existent. Since a metabolic switch has been reported for left heart failure, we sought to describe any potential changes in cardiac fuel metabolism and mitochondrial function in RVF.PAH was induced in S-D rats by a combination of a VEGF-receptor blocker followed by 4 weeks of 10% hypoxia (SuHx).Gene expression was evaluated by RT-PCR and confirmed by western blot. Rats were treated with vehicle/carvedilol for 4 weeks after hypoxia exposure.RV function was measured by echocardiogram and reported as TAPSE.As an initial step, we evaluated the expression of PGC1α, a master regulator of cardiac energetics and mitochondrial biogenesis.SuHx RV tissue had a 60% downregulation of PGC1α when compared to controls (p<0.001).PGC1α target genes codifying enzymes for fatty acid metabolism were decreased, whereas major glycolysis genes were upregulated.These changes strongly correlated with decreased TAPSE (R2=0.77,p<0.001).Furthermore, SuHx RV tissue showed a downregulation of TFAm (a critical regulator for mtDNA maintenance) which was associated with abnormal mitochondrial morphology shown by electron microscopy.Carvedilol treatment, a drug known to improve RVF, completely restored PGC1α expression and reversed the gene expression profile.Our data suggests a switch in cardiac substrate utilization and mitochondrial dysfunction during RVF. We propose carvedilol as a potential treatment to reverse this metabolic switch. ER -