Pulmonary Hypertension Associated with Sickle Cell Disease

 描述(申请人提供)：镰状细胞病是世界上最常见的遗传性单基因疾病之一。肺动脉高压不仅在镰状细胞病中很常见，而且也是镰状细胞病患者发病率和死亡率的主要原因。肺动脉高压发生的机制尚不清楚；我们的目标是确定病态红细胞引起异常肺血流动力学并最终损害右室功能的机制。我们的目标是(1)确定镰状细胞病中红细胞密度增加、溶血和低氧血症对肺血流动力学的急性后果；(2)确定镰状红细胞病对右室后负荷的急性和慢性后果；以及(3)确定镰状细胞病对右室功能和右室-肺血管偶联效率的慢性后果。该项目将是第一个研究镰状细胞病如何改变搏动性肺血流动力学、右室功能和心室-血管相互作用的项目。我们的结果将为了解镰状细胞病中肺动脉高压是如何发展的以及为什么它是镰状细胞病的发病率和死亡率的如此重要的贡献者提供了有价值的见解。

 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.