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oai:repisalud.isciii.es:20.500.12105/133272024-11-28T17:33:41Zcom_20.500.12105_19604com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19605col_20.500.12105_16961col_20.500.12105_16977

00925njm 22002777a 4500 dc Santiago-Vacas, Evelyn author Garcia-Lunar, Ines author Solanes, Nuria author Dantas, Ana Paula author Ascaso, Maria author Jimenez-Trinidad, Francisco Rafael author Ramirez, Jose author Fernandez-Friera, Leticia author Galan-Arriola, Carlos author Sánchez, Javier author Sabate, Manel author Perez-Villa, Felix author Rigol, Montserrat author Pereda, Daniel author Ibáñez, Borja author Garcia-Alvarez, Ana author 2021-02 Right ventricle (RV) dysfunction is a main determinant of morbidity and mortality in postcapillary pulmonary hypertension (PH). However, currently there are not available therapies. Since reduced nitric oxide (NO) availability and cyclic guanylate monophosphate (cGMP) levels are central in this disease, therapies targeting the NO pathway might have a beneficial effect on RV performance. In this regard, sildenafil has shown contradictory results. Our objective was to evaluate the effect of sildenafil on RV performance in an experimental pig model of postcapillary PH induced by a fixed banding of the venous pulmonary confluent. Animals were evaluated by right heart catheterization and cardiac magnetic resonance before randomization and after 8 weeks on sildenafil (n = 8) or placebo (n = 8), and myocardial tissues were analyzed with histology and molecular biology. At the end of the study, animals receiving sildenafil showed better RV performance as compared with those on placebo (improvement in RV ejection fraction of 7.3% ± 5.8% versus -0.6% ± 5.0%, P= 0.021) associated with less apoptotic cells and gene expression related with reduced oxidative stress and increased anti-inflammatory activity in the myocardium. No differences were observed in pulmonary hemodynamics. In conclusion, in a translational large animal model of chronic postcapillary PH, sildenafil improved RV systolic function independently of afterload. Further research with pharmacological approaches able to manipulate the NO-cGMP axis are needed to confirm this potential cardioprotective effect. Transl Res. 2021; 228:64-75 10.1016/j.trsl.2020.08.006 1931-5244 Translational research : the journal of laboratory and clinical medicine 32835905 http://hdl.handle.net/20.500.12105/13327 Effect of sildenafil on right ventricular performance in an experimental large-animal model of postcapillary pulmonary hypertension.