EXERCISE REHABILITATION IN PULMONARY ARTERIAL HYPERTENSION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 本研究的目的是确定肺动脉高压（PAH）患者运动康复计划的安全性和有效性。 肺动脉高压是一种罕见的疾病，导致通过肺部的血流阻塞。血液流动的阻塞导致肺部高血压，并导致他们的心脏右侧衰竭（右心衰竭），呼吸急促和过早死亡。PAH患者的平均年龄为32岁，主要影响女性。目前对患者的药物治疗将存活率从2年的约50%提高到5年的约67%。因此，虽然有效，但这种适度的临床益处并不能使患者享有较长的预期寿命。此外，即使接受治疗，大多数患者的日常活动仍然非常有限，并且仍然呼吸急促。对于预期寿命也有限的慢性左心衰竭（充血性心力衰竭，或CHF）患者，运动康复已成功改善运动能力，力量和耐力。我们假设运动训练也将使PAH所致右心衰竭患者获益。我们还假设，运动训练将有益于这些患者，这是由于1）通过肺的血流增加的效果，导致肺血管内层的剪切应力增加以及血管松弛剂如一氧化氮的产生增加和血管收缩剂如内皮素-1的产生减少; 2）改善了通过肺的血流与输送到肺的空气的匹配（改善了“呼吸效率”）; 3）改善了肌肉做功的能力;以及3）改善了影响生活质量的运动能力。

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.