Microvessels and Heart Problems in Sickle Cell Disease
Microvessels and Heart Problems in Sickle Cell Disease
Background:

 - Small blood vessels (microvessels) in many different organs are affected by diseases such
 as diabetes and atherosclerosis. These microvessels may also be abnormal in people who have
 sickle cell disease. Stiffness of the red blood cells leads to problems in the microvessels
 of the heart and kidneys. However, these problems may not be detected until these organs are
 severely affected. Researchers want to study problems with microvessels in people with and
 without sickle cell disease.

 Objectives:

 - To study how microvessels in the heart and other organs are affected by sickle cell
 disease.

 Eligibility:

 -  Individuals at least 18 years of age who have sickle cell disease.

 -  Healthy volunteers at least 18 years of age.

 Design:

 -  Participants will be screened with a physical exam and medical history. Blood and urine
 samples will be collected.

 -  All participants will have about 3 to 4 hours of testing for the study. Participants
 with sickle cell disease who are having a pain crisis at the time they enter the study
 may be asked to have the testing again when the crisis is over. The repeat testing will
 occur at least 4 weeks after the pain crisis ends.

 -  All participants will have the following tests:

 -  Blood draws to check kidney and liver function, and other blood tests

 -  Measure of blood flow in the brachial (upper arm) artery

 -  Heart ultrasound

 -  Ultrasound scans of arm muscles to study blood flow

 -  Ultrasound scans after taking vasodilators to increase blood flow

 -  Healthy volunteers will also have a magnetic resonance imaging scan. It will show blood
 flow in the heart. This scan will involve another dose of a vasodilator.
Sickle cell disease is the most common genetic disease affecting African-Americans. It is
 characterized by an abnormal hemoglobin S, which polymerizes when deoxygenated leading to red
 cell rigidity and microvascular flow obstruction. Recurrent episodes of ischemia and a
 chronic inflammatory state lead to ischemia-reperfusion injury in multiple vital organ
 systems. Endothelial dysfunction has been demonstrated in patients with sickle cell disease
 and new therapies are targeted specifically towards the endothelium. Contrast ultrasound is a
 non-invasive technique that has been used to assess microvascular flow in coronary artery
 disease, diabetes, and other disease states. We propose to use this technique in sickle cell
 patients to compare their myocardial and skeletal muscle flow with that of normal controls,
 to detect changes during pain crisis, and to compare flow abnormalities with cardiac
 functional abnormalities.
-  INCLUSION CRITERIA:

 -  Adult subject age greater than or equal to 18 years

 -  Able to give written informed consent

 -  For SCD groups, must have confirmed diagnosis of sickle cell disease

 EXCLUSION CRITERIA:

 -  Atrial fibrillation or other irregular rhythm that would preclude adequate image
 acquisition

 -  Subjects with a contraindication for the ultrasound contrast agent.

 -  Pregnant or lactating women

 -  Known obstructive coronary or peripheral vascular disease

 -  SCD subjects at steady-state must not have acute pain crisis requiring intravenous
 analgesics within the prior 4 weeks

 -  SCD subjects in crisis must be within 72 hours of hospital admission

 -  Subjects with contraindications to MRI scanning will complete all other procedures but
 will not undergo the MRI scan. Subjects with an estimated glomerular filtration rate
 of <30 ml/min/1.73 m(2) will not receive gadolinium as per 2011 NHLBI gadolinium
 administration policy.

 -  Subjects with a contraindication to regadenson

 -  Any condition that in the clinical opinion of the investigators renders study
 procedures inadvisable.

 Diagnosis of acute chest syndrome is not an exclusion criteria for this protocol. Subjects
 may be concurrently enrolled in any other protocols with the exception of investigational
 new drug studies.