EXPRESS: Pressure overload induced right ventricular remodeling is not attenuated by the anti-fibrotic agent Pirfenidone

Background - Cardiac fibrosis contributes to development of heart failure in pulmonary hypertension. We aimed to assess development of fibrosis and effects of treatment with the anti-fibrotic agent pirfenidone in pressure overload induced right ventricular (RV) failure. Methods - Wistar rat weanlings were randomized to pulmonary trunk banding (PTB) or sham surgery. One week after the procedure, PTB rats were randomized into two groups with either six weeks on standar chow or treatment with pirfenidone mixed in chow (700 mg/kg/day). RV hemodynamic effects wer evaluated by echocardiography, cardiac MRI and pressure-volume measurements. Sections from th isolated RV, left ventricle, and septum were sampled systematically, and stereological point grids and the nucleator were used to estimate volume of fibrosis and cardiac hypertrophy, respectively. Results - PTB caused RV failure in all rats subjected to the procedure. The volume fraction of fibrosis in RV increased three-fold in PTB rats corresponding to a six-fold increase in total volume of RV fibrosis. Volume fraction of fibrosis and total volume of fibrosis also increased in the septum and in the left ventricle. Pirfenidone reduced body weight but did not improve RV hemodynamics or reduce cardiac fibrosis. RV cardiomyocyte profile area was increased two-fold in PTB rats without any effect of Pirfenidone. Conclusion - RV pressure overload after PTB induced not only RV but also septal and left ventricular fibrosis assessed by stereology. Treatment with pirfenidone reduced body weight but did not reduce the development of cardiac fibrosis or delay the progression of RV failure.