Therapeutic aproaches in PAH with beneficial effects on right ventricular function - preclinical studies

• Autor(a) principal: André Carlos Almeida Balsa
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://hdl.handle.net/10216/150287
• topic: Medicina básica; Basic medicine

Introduction : Pulmonary hypertension (PH) is a progressive condition that affects pulmonary vessels, but its main prognostic factor is right ventricle (RV) function. It is defined as an elevation of mean pulmonary arterial pressure above 20 mmHg at rest. PH group 1 - pulmonary arterial hypertension (PAH) - is a type of disease that primarily benefits from targeted treatment. Many mice/rat models are used for research in PAH, but results fail to translate in clinical trials. Recently, more and more studies are also using pulmonary arterial banding (PAB) - a model of RV disfunction/failure without PH. This review aims to summarize studies that test interventions on PAB and other PH models concomitantly. Methods: articles were searched in Scopus, Web of Science and PubMed, without time or language limitation. Inclusion criteria consisted of pharmacological therapeutical interventions, tested on a PAB and in a PAH animal model. Exclusion criteria were acute interventions, genetic models, and studies without data for PAB group and, at least, one other PH model. Results: multiple tested drugs both improved pulmonary vascular haemodynamics on PH models and ameliorated RV structure and function after PAB, in rats and mice. PH models and PAB frequently exhibited similar results (73,1% concordance) with drugs other than ERA and PDE5i. RV systolic pressure (RVSP) accounted for most differences between PH models and PAB. Only dichloroacetate improved it in PAB animals, whereas 14 out of 19 drugs/combination of drugs improved RVSP in PH models. Results on RV fibrosis, on the other hand, all agreed (12 drugs). Macitentan, sildenafil and tadalafil improved most parameters in PH models, but almost none in PAB animals: only macitentan ameliorated two - Fulton index and TAPSE. Dapagliflozin was the only drug that improved no parameters. Conclusion: this review showed that many drugs currently under research for PAH have a cardioprotective effect on animals that may translate to humans, as well as pulmonary vascular hemodynamics and remodelling benefits. However, results of isolated studies should be interpreted with caution, as small differences in the methodology can lead to noticeable changes in the results. To improve the translational potential of drugs in this field, researchers should test them in multiple models, including PAB, while optimizing induction methods for human disease translation.