RIGHT VENTRICULO-PULMONARY VASCULAR COUPLING IN PAH

绝大多数的肺动脉高压患者，无论病因如何，最终都会死于 这种疾病主要由两个原因引起：猝死或顽固性右心衰竭。虽然已经有了 与肺动脉高压相关的血管异常引起了极大的关注，有一种 对右室在这种疾病中的作用关注相对较少。一个不被认可的人 可能在肺动脉高压患者中发挥重要作用的潜在因素是心室- 继发于肺血管僵硬的血管解偶联，尤其是硬皮病患者。 伴发肺动脉高压。初步数据表明，虽然有一定程度的较大 特发性肺动脉高压中的动脉血管硬化，这种病理明显恶化 在硬皮病相关的肺动脉高压患者中。因为僵硬意味着即使是谦虚 心脏射血增加与较大的动脉后负荷压力有关，它可以限制 心血管储备的机制。这个提议的指导性假设是，脑室- 肺动脉高压患者血管硬化增强，限制心脏 储备和促成劳力性呼吸困难、疲劳，并与死亡率直接相关。这 Proposal使用了许多新技术来研究RV-肺血管相互作用，这种方法可能 证明很容易转化为临床实践，以及研究加强这一点的分子机制 假说，以及对这些通路的干预对本病症状、结局和死亡率的影响 病人群体。此外，这项提议将试图将分子变化与房车故障联系起来，并 重构到RV-PA解偶联的程度，我们将测试这一测量的假设 去偶联将是治疗成功的预测因素。

The vast majority of patients with pulmonary hypertension, regardless of the etiology, ultimately succumb to the disease by two main causes: sudden death or intractable right heart failure. While there has been great focus paid to the vascular abnormalities associated with pulmonary hypertension, there has been a relative paucity of attention given to the role of the right ventricle in this disease. An under-recognized potential factor that may play an important role in patients with pulmonary hypertension is ventricular- vascular uncoupling secondary to pulmonary vascular stiffening especially in patients with scleroderma- associated pulmonary hypertension. Preliminary data suggest that, while there is some degree of large artery vascular stiffening in idiopathic pulmonary arterial hypertension, this pathology is markedly worsened in patients with pulmonary hypertension related to scleroderma. Since stiffening means that even modest increases in cardiac ejection are associated with greater arterial after-load pressures, it can limit mechanisms of cardiovascular reserve. The guiding hypothesis of this proposal is that ventricular- vascular stiffening is enhanced in patients with pulmonary arterial hypertension, limiting cardiac reserve and contributing to exertional dyspnea, fatigue, and is directly related to mortality. This proposal employs many novel techniques to study RV-pulmonary vascular interactions in a way that may prove to be easily translated to clinical practice, as well to study molecular mechanisms that reinforce this hypothesis, and the effect on intervention on these pathways on symptoms, outcomes, and mortality in this patient population. Moreover, this proposal will attempt to tie molecular changes to RV failure and remodeling to the degree of RV-PA uncoupling and we will test the hypothesis that measurement of this uncoupling will be prognostic with regard to treatment success.