Effect of sildenafil on right ventricular performance in an experimental large-animal model of postcapillary pulmonary hypertension.

Translational research : the journal of laboratory and clinical medicine 2021 Feb

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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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Evelyn Santiago-Vacas, Inés García-Lunar, Núria Solanes, Ana Paula Dantas, María Ascaso, Francisco Rafael Jimenez-Trinidad, José Ramirez, Leticia Fernández-Friera, Carlos Galán, Javier Sánchez, Manel Sabaté, Fèlix Pérez-Villa, Montserrat Rigol, Daniel Pereda, Borja Ibañez, Ana García-Álvarez. Effect of sildenafil on right ventricular performance in an experimental large-animal model of postcapillary pulmonary hypertension. Translational research : the journal of laboratory and clinical medicine. 2021 Feb;228:64-75