Pulmonary Hypertension Associated with Sickle Cell Disease

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 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.