Urban-training Intervention in Pulmonary Hypertension (UTHAP)

Pulmonary rehabilitation is effective in the treatment of pulmonary hypertension (PH). However, the beneficial effects of such intervention have been seen to disappear over time in other chronic diseases. The objective of the project is to evaluate the efficacy of an urban exercise program after a rehabilitation program and to identify possible determinants of sustainability of the effect, both in patients and in a murine experimental model. Methodology: 1) Study in humans: randomized study (urban training) in 80 patients with PH. The main variable is the improvement in physical activity measured by accelerometry at 12 months. Improvements in bioimpedance and aerobic capacity will be analysed as secondary variables, as well as possible determinants of vascular function that guarantee the sustainability of the effect (pulse wave velocity, endothelial function, metabolic profile and other plasma biomarkers), and all of them will be correlated with the evolution of the disease (admission due to clinical deterioration). 2) Studies in a murine experimental model: Mice with pulmonary hypertension induced by the administration of SU5416 (sugen) and exposure to hypoxia for 3 weeks will be studied after a three-week rehabilitation program. Half of them will exercise 1-2 days a week for 4 more weeks. At the end of the program, the right ventricular pressure will be measured and subsequently the animals will be sacrificed. Morphometric studies will be performed on lung, cardiac and muscular tissue. Vascular endothelial function and autophagy will be also measured. The differences in these variables between the different experimental groups will be analysed.