The purpose of this study is to see if some people with postural tachycardia syndrome (POTS) have higher levels of immune proteins (autoantibodies) directed against receptors of the autonomic nervous system, and if these autoantibodies make a difference in their POTS symptoms. The investigators also want to see if the levels of these autoantibodies stay the same over time.
Postural tachycardia syndrome (POTS) is a debilitating disorder resulting from cardiovascular autonomic dysfunction, has many causes and is very difficult to treat effectively. The investigators have identified the presence of autoantibodies (immune proteins) directed against some receptors of the autonomic nervous system that can cause patient's symptoms on standing. The present study is designed to test the hypothesis that patients with POTS harbor functional autoantibodies to adrenergic receptors that lead to an excessive tachycardia characteristic of POTS. For this purpose, this study will define the prevalence, burden, and the in vivo physiological significance of these adrenergic antibodies in a well-phenotyped and representative cohort of patients with POTS and a matched cohort of healthy control subjects, and will characterize the stability of these autoantibodies over time in affected POTS patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
58
Phenylephrine is a selective α1-adrenergic receptor agonist. It will be given in IV bolus injections starting from 12.5 ug. Incremental doses will be given every \~3 min up to 800 ug or until systolic blood pressure increases by 25 mmHg
Isoproterenol is non-selective beta-adrenergic agonist. It will be given in IV bolus injections starting from 0.025 ug. Incremental doses will be given every \~3 min until heart rate increases by 25 bpm. This intervention is optional.
Using injection of iodinated I-131 tagged human serum albumin nominally 25 micro-Ci of radiation, blood samples are drawn before and 30 minutes after injection.
Blood pressure and heart rate will be measured while supine and then while standing for up to 30 minutes. Blood will be drawn in each position to measure hormones that regulate blood pressure and blood volume. An additional sample will be collected in the supine position for the autoantibody assessment.
Blood pressure, heart rate and ECG monitoring for 24 hours
The QSART assesses the ability of sympathetic nerve terminals in the skin to release acetylcholine and increase sweat production. The test is performed at 4 sites over the forearm, proximal lateral leg, medial distal leg and proximal foot.
The autonomic function tests will determine how well the autonomic nervous system regulates blood pressure and heart rate. These tests include breathing deeply for two minutes, breathing fast for 30 seconds, maintaining a handgrip for 3 minutes, breathing against pressure for 15 seconds, and placing the hand in ice water for 1 minute. In addition, participants will be tilted up on a tilt table for up to 10 minutes while recording their heart rate, blood pressure and cardiac output.
Cardiac output will be measured using the rebreathing technique (Innocor)
Splanchnic capacitance will be assessed using cpap and body impedance to construct pressure volume curves
microneurography will be measured in the peroneal nerve to assess sympathetic activity.
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Autonomic Dysfunction Center
Nashville, Tennessee, United States
Autoantibody levels
Blood samples collected while supine during the posture study will be analyzed for autoantibody positivity in POTS patients and control subjects.
Time frame: up to 10 minutes
Blood pressure after phenylephrine boluses
Time frame: 1-2 minutes after bolus injections
Heart rate after isoproterenol boluses
Time frame: 1-2 minutes after bolus injections
Orthostatic change in heart rate
Difference between standing and supine heart rates.
Time frame: up to 10 minutes
Blood pressure response during phase IV of the Valsalva maneuver
Time frame: up to 10 minutes
Hear rate response during phase IV of the Valsalva maneuver
Time frame: up to 10 minutes
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.