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：
8184771
负责人：
Naomi C Chesler
金额：
$ 63.99万
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/8184771
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 PUBLIC HEALTH RELEVANCE: Pulmonary arterial hypertension (PAH) is a poorly understood disease of the arteries of the lung that ultimately leads to heart failure. The benefits of exercise in current clinical management of PAH are highly controversial, largely because its effects on heart function are unknown. We propose to measure the impact of exercise on blood flow and heart function to improve our understanding of this disease, identify patients who are likely to benefit from exercise, and develop novel predictors of disease progression.

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衰竭。最近，大型肺动脉的刚度增加被确定为PAH死亡率的强大预测指标。小动脉的刚度增加也可能导致疾病进展。近端和远端动脉僵硬对患者运动能力和受益于运动能力的影响尚不清楚。我们假设近端动脉僵硬是通过低效率的血液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僵硬的限制锻炼能力。这项研究的目标是量化不同类型的PAH的右心室 - 肺血管相互作用，以确定这些与PAH进展的相互作用的时间变化，并量化运动对右心室功能的影响。我们对与全身性硬化（SSC）的PAH亚种群特别感兴趣，因为我们预计该组的动脉僵硬比其他群体较差，因此右心室肺血管相互作用效率更低，这构成了它们较差的预后。我们的目标是：目标1。量化PAH患者的肺动脉僵硬，右心室功能与心室血管相互作用的效率之间的关系。目的2。量化运动对PAH患者中肺动脉僵硬，肺部耐药性，右心室功能以及心室血管相互作用的效率的影响。目的3。研究IPAH和CTEPH犬模型中心室血管相互作用效率丧失的进展。最近，研究PAH的临床和科学社区被指控更全面地研究心肺系统，尤其是在使用SSC的PAH亚群中。我们的目标是研究PAH中右心肺血管相互作用的血液动力学机制，PAH亚型之间的差异以及运动对PAH心室和血管功能的影响以及PAH中的相互作用。重要的是，我们的结果可能会导致一种新颖的疾病“生理标志”，该疾病可以使临床医生更好地识别有患有心室血管功能障碍风险的PAH患者，并确定谁可能会从运动训练中受益。 1 公共卫生相关性：肺动脉高压（PAH）是一种对肺动脉的了解鲜为人知，最终导致心力衰竭。运动在当前对PAH的临床管理方面的好处是高度争议的，主要是因为其对心脏功能的影响尚不清楚。我们建议衡量运动对血流和心脏功能的影响，以提高我们对这种疾病的理解，确定可能从运动中受益的患者，并发展出疾病进展的新预测指标。