Abstract 17600: Carvedilol Improves Left and Right Ventricular Fibrosis and Function Through Abrogation of Tgfβ1-ctgf Signaling in a Rat Persistent Right Ventricular Afterload Model

Background: Left ventricular (LV) function influences outcomes in right ventricular (RV) failure. Carvedilol reduces mortality in LV failure and improves right ventricular (RV) function in experimental pulmonary arterial hypertension (PAH). However, its impact on ventricular-ventricular interactions and LV function in RV afterload is unknown. We investigated effects of carvedilol on biventricular fibrosis and function in a rat model of persistent PAH. Methods and Results: Rats were randomized into 3 groups: Sham controls, PAH and PAH+carvedilol. Severe PAH was induced by 60mg/kg subcutaneous monocrotaline. In the treatment group, oral carvedilol (15mg/kg/d) was started 2-weeks after monocrotaline injection and continued for 3-weeks until the terminal experiment. Echocardiography and exercise performance were performed at baseline and repeated at the terminal experiment with hemodynamic measurements. LV and RV myocardium were analyzed for hypertrophy, fibrosis and molecular signaling by protein and mRNA an...