2026-06-14T03:54:06Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
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
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación ProCNIC
funder
Centro de Investigación Biomédica CELLEX del IDIBAPS
funder
Government of Catalonia (España)
2021-08-31T08:45:31Z
2021-08-31T08:45:31Z
2021-02
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
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.
eng
Effect of sildenafil on right ventricular performance in an experimental large-animal model of postcapillary pulmonary hypertension.
journal article
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EffectOfSildenafilOn_2021.pdf
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EffectOfSildenafilOn_2021.pdf.txt