Right Ventricular-Pulmonary Vascular Interactions in Pulmonary Hypertension

描述（由申请人提供）：肺动脉高压（PAH）是一种进行性和快速致命的疾病，即使采用现代治疗。死因通常是右心室衰竭。最近，大肺动脉僵硬度增加被认为是PAH死亡率的一个强有力的预测因素。小动脉僵硬度的增加也可能导致疾病进展。近端和远端动脉硬化对患者运动能力和受益能力的影响尚不清楚。我们假设近端动脉硬化是通过低效的血流动力学相互作用导致右心室功能障碍的原因。我们还假设远端动脉硬化限制了运动能力。本研究的目的是量化不同类型PAH的右心室-肺血管相互作用，确定这些相互作用与PAH进展的时间变化，并量化运动对右心室功能的影响。我们对PAH合并系统性硬化症（SSc）的亚群特别感兴趣，因为我们预计这一组动脉硬化比其他组更严重，因此右室-肺血管相互作用更无效，这是他们预后较差的原因。我们的目标是：量化肺动脉僵硬度、右心室功能和PAH患者心室-血管相互作用效率之间的关系。目标2。量化运动对肺动脉高压患者肺动脉僵硬度、肺血管阻力、右心室功能和心室血管相互作用效率的影响。目标3。研究犬IPAH和CTEPH模型中脑室-血管相互作用效率丧失的进展。研究多环芳烃的临床和科学界最近被要求更全面地研究心肺系统，特别是在多环芳烃合并SSc的亚群中。我们的目的是研究PAH中右心室-肺血管相互作用的血流动力学机制，PAH亚型之间的差异以及运动对PAH中心室和血管功能和相互作用的影响。重要的是，我们的结果可能会导致一种新的疾病“生理标志物”，使临床医生能够更好地识别有心室血管功能障碍风险的PAH患者，并确定谁可能从运动训练中受益。1

DESCRIPTION (provided by applicant): Pulmonary arterial hypertension (PAH) is a progressive and rapidly fatal disease, even with modern therapies. The cause of death is typically right ventricular failure. Recently, increased stiffness of the large pulmonary arteries was identified as a powerful predictor of mortality in PAH. Increased stiffness of the small arteries may also contribute to disease progression. The effects of proximal and distal arterial stiffening on a patient's exercise capacity and ability to benefit from exercise are unknown. We hypothesize that proximal arterial stiffening is responsible for right ventricular dysfunction via inefficient hemodynamic interactions. We also hypothesize that distal arterial stiffening limits exercise capacity. The goals of this study are to quantify right ventricular-pulmonary vascular interactions in different types of PAH, to determine the temporal changes in these interactions with PAH progression and to quantify the effects of exercise on right ventricular function. We have a particular interest in the subpopulation of PAH with systemic sclerosis (SSc) because we anticipate that this group has worse arterial stiffening than other groups, and consequently more inefficient right ventricular-pulmonary vascular interactions, which account for their worse prognosis. Our aims are: Aim 1. To quantify the relationships between pulmonary arterial stiffness, right ventricular function and the efficiency of ventricular-vascular interactions in patients with PAH. Aim 2. To quantify the effects of exercise on pulmonary arterial stiffness, pulmonary vascular resistance, right ventricular function and the efficiency of ventricular-vascular interactions in patients with PAH. Aim 3. To investigate the progression of loss of efficiency of ventricular-vascular interactions in canine models of IPAH and CTEPH. The clinical and scientific communities investigating PAH were recently charged with studying the cardiopulmonary system more comprehensively, especially in subpopulation of PAH with SSc. Our goals are to investigate the hemodynamic mechanisms of right ventricular-pulmonary vascular interactions in PAH, differences among PAH subtypes and the effects of exercise on ventricular and vascular function and interactions in PAH. Importantly, our results may lead to a novel "physiomarker" of disease that could enable clinicians to better identify PAH patients who are at risk for ventricular-vascular dysfunction and determine who will likely benefit from exercise training. 1