LAUSR

Right ventricular (RV) dysfunction determines mortality in patients with pulmonary arterial hypertension (PAH) and RV pressure-loading. Experimental models commonly utilize Sugen-Hypoxia (SuHx)-induced PAH, monocrotaline (MCT)-induced PAH or pulmonary artery banding (PAB). As PAH models cannot interrogate RV-effects or therapies independent of pulmonary vascular effects, we aimed to compare RV function and fibrosis in experimental PAB versus PAH. Thirty rats were randomized to either sham controls, PAB, SuHx or MCT-induced PAH. RV pressures and function were assessed by high-fidelity pressure-tipped catheters and by echocardiography. RV myocyte hypertrophy, fibrosis and capillary density were quantified from hematoxylin-eosin, picrosirius red (PSR) stained and CD31 immunostained RV sections, respectively. RV pressures and the RV/LV pressure-ratio were significantly increased in all 3 groups to a similar degree (PAB 65±17mmHg, SuHx 72±16mmHg and MCT 70±12mmHg) versus controls (23±2mmHg, all P<0.01). RV dilatation, hypertrophy and fibrosis were similarly increased, and capillary density decreased, in the 3 models (RV fibrosis; PAB 13.3±3.6%, SuHx 9.8±3.0% and MCT 10.9±2.4% vs control 5.5±1.1%, all p<0.05). RV function was similarly decreased in all models versus controls. We observed comparable RV dilatation, hypertrophy, systolic and diastolic dysfunction, fibrosis and capillary rarefaction in rat models of PAB, SuHx- and MCT-induced PAH. These results suggest that PAB, when sufficiently severe, induces features of maladaptive RV remodeling and can be used to investigate RV pathophysiology, and therapy effects independent of pulmonary vascular resistance.