BIBF1000 is a small molecule tyrosine kinase inhibitor targeting Vascular Endothelial Growth Factor Receptor (VEGFR), Fibroblast Growth Factor Receptor (FGFR) and Platelet Derived Growth Factor Receptor (PDGFR) and is a powerful inhibitor of fibrogenesis. BIBF1000 is very similar to BIBF1120 (Nintedanib), a drug recently approved for the treatment of Idiopathic Pulmonary Fibrosis (IPF). A safety concern pertaining to VEGFR, FGFR and PDGFR inhibition is the possible interference with right ventricular (RV) responses to an increased afterload, which could adversely affect clinical outcome in IPF patients who developed pulmonary hypertension. We tested the effect of BIBF1000 on the adaptation of the RV in rats subjected to mechanical pressure overload. BIBF1000 was administered for 35 days in pulmonary artery banded (PAB) rats. RV adaptation was assessed by echocardiography, pressure volume loop analysis, histology and determination of atrial natriuretic peptide (ANP) expression. BIBF1000 treatment resulted in growth attenuation but had no effects on RV function after PAB, given absence of changes in cardiac index, end systolic elastance, connective tissue disposition and capillary density. We conclude that in this experimental model of increased afterload, combined VEGFR, FGFR and PDGFR inhibition does not hamper RV adaptation to pressure overload.
- experimental Pulmonary Hypertension
- pulmonary artery banding
- tyrosine kinase inhibitor
- cardiac remodeling
- Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology