Nitric Oxide to Improve Blood Flow in Sickle Cell Disease

Sickle cell anemia is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15% of African-Americans are homozygous for sickle cell disease, and 8% have sickle cell trait. Acute pain crisis and acute chest syndrome are common complications of sickle cell anemia. Inhaled nitric oxide (NO) has been proposed as a possible therapy for the acute chest syndrome. Anecdotally, NO has been described to rapidly improve the hypoxemia and the clinical course of the acute chest syndrome. Furthermore, a number of recent studies have suggested that NO may have a favorable impact on sickle red cells at the molecular level and could improve the abnormal microvascular perfusion that is characteristic of sickle cell anemia. This clinical trial is designed to test the hypotheses that 1) individuals with sickle cell anemia have endothelial dysfunction with reduced local synthesis and release of NO, that may reduce regional perfusion at rest and impair the vasodilator response to stress, and 2) during NO inhalation, delivery of NO bound to hemoglobin will be enhanced and will improve these abnormalities in regional vascular perfusion. Studies will be performed on untreated sickle cell anemia patients and on patients managed with chronic hydroxyurea therapy. Demonstration of improved regional perfusion with NO therapy could have significant implications for patient management during acute pain crisis and the acute chest syndrome.