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Andersen S, Birkmose Axelsen J, Ringgaard S, et al. Pressure overload induced right ventricular remodeling is not attenuated by the anti-fibrotic agent pirfenidone. Pulm Circ. 2019;9(2):2045894019848659doi: 10.1177/2045894019848659.
Andersen, S., Birkmose Axelsen, J., Ringgaard, S., Randel Nyengaard, J., Holm Nielsen, S., Genovese, F., Asser Karsdal, M., Adler Hyldebrandt, J., Brandt Sørensen, C., de Man, F. S., Jan Bogaard, H., Erik Nielsen-Kudsk, J., & Andersen, A. (2019). Pressure overload induced right ventricular remodeling is not attenuated by the anti-fibrotic agent pirfenidone. Pulmonary circulation, 9(2), 2045894019848659. https://doi.org/10.1177/2045894019848659
Andersen, Stine, et al. "Pressure overload induced right ventricular remodeling is not attenuated by the anti-fibrotic agent pirfenidone." Pulmonary circulation vol. 9,2 (2019): 2045894019848659. doi: https://doi.org/10.1177/2045894019848659
Andersen S, Birkmose Axelsen J, Ringgaard S, Randel Nyengaard J, Holm Nielsen S, Genovese F, Asser Karsdal M, Adler Hyldebrandt J, Brandt Sørensen C, de Man FS, Jan Bogaard H, Erik Nielsen-Kudsk J, Andersen A. Pressure overload induced right ventricular remodeling is not attenuated by the anti-fibrotic agent pirfenidone. Pulm Circ. 2019 Apr-Jun;9(2):2045894019848659. doi: 10.1177/2045894019848659. PMID: 30997866; PMCID: PMC6540527.
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Pulm Circ. 2019 Apr-Jun;9(2):2045894019848659. doi: 10.1177/2045894019848659.

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

Pulmonary circulation

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

Affiliations

  1. 1 Department of Cardiology, Aarhus University Hospital, Denmark.
  2. 2 MR Centre, Aarhus University Hospital, Denmark.
  3. 3 Core Center for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine; Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Denmark.
  4. 4 Fibrosis Biology and Biomarkers Research, Nordic Bioscience A/S, Herlev, Denmark.
  5. 5 Deparment of Biomedicine and Biotechnology, Technical University of Denmark, Lyngby, Denmark.
  6. 6 Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Denmark.
  7. 7 Department of Clinical Medicine, Aarhus University, Denmark.
  8. 8 Department of Pulmonology, Amsterdam UMC, The Netherlands.

PMID: 30997866 PMCID: PMC6540527 DOI: 10.1177/2045894019848659

Abstract

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.

Keywords: animal models; remodeling; right ventricular function and dysfunction

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