Pressure overload induced right ventricular remodeling is not attenuated by the anti-fibrotic agent pirfenidone

Cardiac fibrosis contributes to the development of heart failure in pulmonary hypertension. We aimed to assess the development of fibrosis and the effects of treatment with the anti-fibrotic agent pirfenidone in pressure overload induced right ventricular (RV) failure. 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 standard chow or treatment with pirfenidone mixed in chow (700 mg/kg/day). RV hemodynamic effects were evaluated by echocardiography, cardiac magnetic resonance imaging (MRI), and pressure-volume measurements. Sections from the isolated RV, left ventricle, and septum were sampled systematically; stereological point grids and the nucleator were used to estimate volume of fibrosis and cardiac hypertrophy, respectively. PTB caused RV failure in all rats subjected to the procedure. The volume fraction of fibrosis in the RV increased threefold in PTB rats corresponding to a sixfold 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 twofold in PTB rats without any effect of pirfenidone. 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.

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Topics

Animal Models
Pulmonary Vascular Remodeling
Right Ventricle: Structure, Function and Dysfunction

Authors

Stine Andersen, Julie Birkmose Axelsen, Steffen Ringgaard, Jens Randel Nyengaard, Signe Holm Nielsen, Federica Genovese, Morten Asser Karsdal, Janus Adler Hyldebrandt, Charlotte Brandt Sørensen, Frances S. de Man, Harm Jan Bogaard, Jens Erik Nielsen-Kudsk, Asger Andersen

Published in:

Pulmonary Circulation Vol 9: No 2 cover image

June 2019

Pulmonary Circulation Vol 9: No 2

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