Evaluation of Chronic Orthostatic Intolerance
This study will conduct tests with patients with primary chronic orthostatic intolerance (COI) to learn more about this disorder of the autonomic nervous system.
Healthy normal volunteers and patients 18 years of age and older with COI may be eligible for this study. Participants undergo one or more of the following tests and procedures:
- Blood studies, including arterial catheter insertion to measure blood pressure and collect arterial blood samples, blood flow studies using sensors applied to the skin and a pressure cuff around a limb, blood volume studies using injection of radioactively labeled human serum albumin and gene studies to look for genetic abnormalities associated with certain proteins.
- Imaging studies, including CT scan of the adrenal glands, heart ultrasound, and PET scanning.
- Microdialysis to measures levels of chemicals in the body fluid of certain tissues. A thin tube is inserted into the skin and a solution is passed through it. Chemicals in the body tissues enter the solution in the tube. The solution is collected and the chemical levels are measured.
- Neck suction. Neck suction is applied to test a reflex the brain uses to regulate blood pressure.
- Perometry. Limb volume is measured using an infrared light that moves up the limb.
- Quantitative sudomotor axon reflex test to evaluate an aspect of autonomic nervous system function. A small amount of a brain chemical (acetylcholine) is applied to the skin with a tiny amount of electricity, and the sweat in a nearby patch of skin is measured.
- Skin electrical conduction test using sensors on the skin to measure sweat production.
- Skin and core temperature measurements using sensors on the skin and in the ear canal.
- Tilt table test. The subject lies on a table, secured with straps around the chest and legs. Sensors are placed on the arms and chest to monitor blood pressure, pulse rate, and heart rhythm. A catheter is placed in a vein in each arm to collect blood samples and give drugs. Another catheter is placed in an artery to draw blood and monitor blood pressure. The subject is given an infusion of norepinephrine and epinephrine, and baseline measures and blood samples are taken. The table is tilted upright and more measurements and blood samples are taken at intervals for up to 30 minutes. The table is returned to a horizontal position and additional measurements and samples may be taken.
Drugs may be administered during the tests, including acetylcholine, epinephrine, and norepinephrine, radioactive chemicals used in imaging studies, and drugs that affect blood vessels, heart rate, and force of heart contractions.
|Official Title:||Clinical Laboratory Evaluation of Chronic Orthostatic Intolerance|
|Study Start Date:||September 2003|
|Estimated Study Completion Date:||August 2008|
This protocol is to identify and characterize distinct types of chronic orthostatic intolerance (COI). COI can be a manifestation of primary chronic autonomic failure, which is covered under a separate protocol. The present protocol concerns patients with COI who under resting conditions have intact sympathetic neurocirculatory function. COI can reflect different pathophysiologic mechanisms; until now, few studies have attempted to distinguish these mechanisms in individual patients. We hypothesize that results of clinical assessment and physiologic, chemical, pharmacologic, and imaging tests will reveal internally consistent patterns that distinguish particular forms of COI. We wish to determine the relative frequencies of these forms in a referral population. The first phase of testing is to identify sympathetic neurocirculatory failure, baroreflex failure, and secondary causes of COI (hypovolemia, excessive orthostatic venous pooling, or excessive orthostatic extravasation). In a subsequent inpatient phase, tilt table testing is done, with concurrent hemodynamic and chemical measurements, to confirm subtypes of postural tachycardia syndrome and neurocardiogenic syncope. The results of these evaluations will be used for stratification of specific, pathophysiologically defined diagnostic groups for therapeutic protocols. In an off-site study, we will evaluate members of a large family where COI seems to be transmitted as an autosomal dominant trait.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Hospital Sacre-Coeur de Montreal|
|University of Ottawa Heart Institute|