Right Ventricular-Pulmonary Vascular Interactions in Pulmonary Hypertension

肺动脉高压中右心室-肺血管的相互作用

基本信息

批准号：
8317371
负责人：
Naomi C Chesler
金额：
$ 60.74万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-15 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8317371
关键词：
Accounting Affect Animal Experiments Arteries Blood Vessels Blood flow Canis familiaris Cardiopulmonary Cause of Death Cessation of life Charge Chronic Clinical Clinical Data Clinical Management Communities Data Dependence Disease Disease Progression Distal Exercise Failure Functional disorder Goals Heart failure Lead Lung Measures Modeling Outcome Patients Pharmaceutical Preparations Progressive Disease Pulmonary Hypertension Pulmonary Vascular Resistance Pulmonary artery structure Quality of life Rest Right Ventricular Dysfunction Right Ventricular Function Right ventricular structure Risk Symptoms Systemic Scleroderma Testing Time Time Study Training Ventricular Ventricular Ejection Fractions arterial stiffness cardiopulmonary system clinically relevant disorder subtype heart function hemodynamics improved insight interest mortality novel outcome forecast prevent prognostic pulmonary arterial hypertension treatment strategy

项目摘要

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

描述（由申请人提供）：即使采用现代疗法，肺动脉高压（PAH）也是一种进行性且迅速致命的疾病。死亡原因通常是右心室衰竭。最近，大肺动脉僵硬度的增加被认为是 PAH 死亡率的有力预测因素。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从运动中受益的能力的影响尚不清楚。我们假设近端动脉硬化通过低效的血流动力学相互作用导致右心室功能障碍。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 中右心室-肺血管的相互作用，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。我们对患有系统性硬化症 (SSc) 的 PAH 亚群特别感兴趣，因为我们预计该群体的动脉硬化程度比其他群体更严重，因此右心室-肺血管相互作用更加低效，这也是其预后较差的原因。我们的目标是：目标 1. 量化 PAH 患者肺动脉硬度、右心室功能和心室-血管相互作用效率之间的关系。目标 2. 量化运动对 PAH 患者肺动脉僵硬度、肺血管阻力、右心室功能以及心室-血管相互作用效率的影响。目标 3. 研究 IPAH 和 CTEPH 犬模型中心室-血管相互作用效率损失的进展情况。研究 PAH 的临床和科学界最近负责更全面地研究心肺系统，特别是患有 SSc 的 PAH 亚群。我们的目标是研究 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心室和血管功能以及 PAH 中相互作用的影响。重要的是，我们的结果可能会产生一种新的疾病“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