Effect of sildenafil on right ventricular performance in an experimental large-animal model of postcapillary pulmonary hypertension
| Autor: | Montserrat Rigol, Borja Ibanez, Manel Sabaté, Inés García-Lunar, María Ascaso, Francisco Rafael Jimenez-Trinidad, C Galan, Núria Solanes, Félix Pérez-Villa, Leticia Fernández-Friera, Javier Sanchez, Ana García-Álvarez, Ana Paula Dantas, Daniel Pereda, José Ramírez, Evelyn Santiago-Vacas |
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| Přispěvatelé: | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Fundación ProCNIC, Centro de Investigación Biomédica CELLEX del IDIBAPS, Government of Catalonia (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Sildenafil Swine Heart Ventricles Hypertension Pulmonary Vasodilator Agents Enfermedad cardiovascular Disfunción ventricular derecha Placebo medicine.disease_cause Sildenafil Citrate Nitric oxide 03 medical and health sciences chemistry.chemical_compound Tratamiento médico 0302 clinical medicine Afterload Physiology (medical) Internal medicine Medicine Animals Ejection fraction business.industry Biochemistry (medical) Public Health Environmental and Occupational Health General Medicine Aparato respiratorio medicine.disease Pulmonary hypertension Disease Models Animal 030104 developmental biology medicine.anatomical_structure chemistry Ventricle Citrato de sildenafil 030220 oncology & carcinogenesis Cardiology business Hipertensión pulmonar Oxidative stress |
| Popis: | 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. This work was partially funded by the grant Ajut a la Recerca “Josep Font” 2015 (to Dr. Santiago-Vacas) and by Fondo Europeo de Desarrollo Regional (FEDER) Instituto de Salud Carlos III-Fondo de Investigación Sanitaria PI17/00995 (to Dr. García-Álvarez). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Part of this work was developed at the Centre de Recerca Biomèdica Cellex, IDIBAPS, Barcelona. The IDIBAPS belongs to the CERCA Programme and receives partial funding from the Generalitat de Catalunya Sí |
| Databáze: | OpenAIRE |
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