Pulmonary Hypertension Associated with Sickle Cell Disease

与镰状细胞病相关的肺动脉高压

• 批准号: 9251902
• 负责人: Naomi C Chesler
• 金额: $ 19.13万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9251902
• 关键词: Acute; Adult; Affect; Arginine; Biological; Blood Vessels; Blood flow; Cardiac Output; Carotid Arteries; Cell Density; Cells; Chemicals; Chronic; Coupling; Data; Development; Dilatation - action; Disease; Dose; Endothelin-1; Erythrocytes; Goals; Heart Rate; Hemoglobin; Hemolysis; Heritability; Hypoxemia; Impairment; Inferior; Infusion procedures; Lead; Long-Term Effects; Lung; Lung diseases; Measures; Mechanics; Methods; Molecular; Morbidity - disease rate; Mus; Nitric Oxide; Nitric Oxide Signaling Pathway; Nystatin; Oxygen; Patient-Focused Outcomes; Patients; Physiologic intraventricular pressure; Prevalence; Prevention strategy; Pulmonary Hypertension; Pulmonary Vascular Resistance; Right Ventricular Dysfunction; Right Ventricular Function; Right Ventricular Hypertrophy; Risk; Sickle Cell; Sickle Cell Anemia; Sudden Death; Testing; Time; Vascular Diseases; Vena caval structure; Ventricular; Ventricular Ejection Fractions; Work; arginase; arterial stiffness; base; coronary fibrosis; density; electric impedance; hemodynamics; hydroxyurea; in vivo; insight; mortality; novel; novel strategies; public health relevance; sickling; treatment strategy

 DESCRIPTION (provided by applicant): Sickle cell disease is one of the most common heritable monogenetic diseases in the world. Pulmonary hypertension is not only common in sickle cell disease but also a leading cause of morbidity and mortality in patients with sickle cel disease. The mechanisms by which pulmonary hypertension develops remain unclear; our goal is to identify the mechanical mechanisms by which sickled red blood cells cause abnormal pulmonary blood flow dynamics and ultimately impair right ventricular function. Our aims are (1) to determine the acute consequences of increased red blood cell density, hemolysis and hypoxemia, which occur in sickle cell disease, on pulmonary hemodynamics; (2) to determine the acute and chronic consequences of sickled red blood cells on right ventricular afterload; and (3) to determine the chronic consequences of sickle cell disease on right ventricular function and right ventricular-pulmonary vascular coupling efficiency. This project will be the first to investigate how pulsatile pulmonary hemodynamics, right ventricular function, and ventricular-vascular interactions are altered with sickle cell disease. Our results will lend valuable insight into how pulmonary hypertension develops in sickle cell disease and why it is such an important contributor to morbidity and mortality in sickle cell disease.

 描述（由适用提供）：镰状细胞疾病是世界上最常见的遗传单基因疾病之一。肺部高血压不仅在镰状细胞疾病中常见，而且是镰状疾病患者发病率和死亡率的主要原因。肺高血压发育的机制尚不清楚。我们的目标是确定谨慎的红色血细胞引起异常肺血流动力学并最终损害右心室功能的机械机制。我们的目的是（1）确定在肺部血流动力学上发生的红细胞密度，溶血和低氧血症的急性后果； （2）确定镰状细胞病在右心室后负荷上的急性和慢性后果； （3）确定镰状细胞疾病对右心室功能和右心肺血管偶联效率的慢性后果。该项目将是第一个研究脉冲肺血液动力学，右心室功能和心室血管相互作用如何通过镰状细胞疾病改变的一个项目。我们的结果将为镰状细胞疾病中的肺动脉高压如何发展以及为什么这是镰状细胞疾病的发病和死亡的重要促进者提供宝贵的见解。