This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to determine the safety and efficacy of an exercise rehabilitation program in patients with pulmonary arterial hypertension (PAH). PAH is a rare disease that results in blockage of blood flow through the lungs. The blockage of blood flow results in high blood pressure in the lungs, and causes the right side of their heart to fail (right heart failure), shortness of breath and early death. The average age of patients with PAH is 32 years, and it affects mostly women. Current medical therapy for patients improves survival from about 50% at 2 years to about 67% at 5 years. Thus, while effective, this modest clinical benefit does not enable patients to enjoy a long life expectancy. In addition, even with treatment, most patients are still very limited in their daily activities and remain short of breath. In patients with chronic left heart failure (congestive heart failure, or CHF) whose life expectancy is also limited, exercise rehabilitation has been successful at improving exercise capacity, strength, and endurance. We hypothesize that exercise training will also benefit patients with right heart failure due PAH. We also hypothesize that exercise training will benefit these patients due to 1) the effect of increased blood flow through the lungs resulting in increased shear stress in the lining of the blood vessels of the lungs as well as increased production of blood vessel relaxors such as Nitric Oxide and decreased production of blood vessel constrictors such as endothelin-1;2) improved matching of blood flow through the lungs with air delivery to the lungs (improved """"""""ventilatory efficiency"""""""");3) improved ability of the muscles to perform work;and 3) improved exercise capacity affecting quality of life.
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