Late Breaking Abstract - Development of an animal model for group 3 Pulmonary Hypertension

Experimental lung fibrogenic injury was induced in male Sprague-Dawley rats, randomly receiving a single intratracheal instillation of bleomycin sulphate (B, 7.5U/Kg) or saline (S). Echocardiographic and haemodynamic studies, as well as bronchoalveolar lavage fluid (BALF), blood and organ collection were performed 3 weeks after B instillation. Biochemical and histological studies confirmed the development of fibrosis in B-treated lungs, as shown by the increase in hydroxyproline content, as well as an increase in Sirius red stained areas both in proximal and distal lung tissue. Interestingly, in addition to parenchymal fibrosis, echocardiographic and haemodynamic studies revealed that B group developed mild PH, as shown by increased right ventricular end-systolic pressure (RVESP), mean pulmonary artery pressure (mPAP) and total pulmonary vascular resistance (TPVR). There were also indices of compromised right ventricular function, with decreased cardiac output (CO) and tricuspid annular plane systolic excursion (TAPSE). Moreover, rats submitted to B presented RV hypertrophy as shown by the Fulton Index. In addition and confirming PH development in these animals, vascular remodelling was observed in the B group, as shown by the increase in the arterial wall area. Our data shows the successful implementation of a rodent model that mimics combined lung (parenchymal) fibrosis and PH, with most of the features seen in human, such as lung and arterial remodelling, increased mPAP and compromised RV function, allowing future research to be focused on pathological mechanisms and possible new therapeutic targets.