Vagal Stimulation in POTS

This study will test the hypothesis that impairment of the parasympathetic nervous system
contributes to the symptoms of POTS and that stimulation of this part of the nervous system
improves the excessive increase in heart rate, standing tolerance and inflammation in
patients with POTS. For this purpose, the investigators will use electrical stimulation of a
nerve in the skin of the earlobe (transcutaneous vagal nerve stimulation) and two medications
that increase the levels of acetylcholine (a neurotransmitter) in the central or peripheral
nervous system (galantamine and pyridostigmine, respectively) to increase the activity of the
parasympathetic nervous system.

Screening Procedures: Potential participants will be screened in the Vanderbilt Autonomic
Dysfunction Center (ADC). Medications affecting heart rate, blood pressure, blood volume,
inflammatory markers and the autonomic nervous system will be withdrawn for at least five
half-lives before studies. Patients will undergo a complete history and physical examination,
ECG, routine clinical laboratory analyses and a blood pregnancy test for women of
childbearing potential. Autonomic testing including a posture study with plasma
catecholamines is then performed to determine if they meet the inclusion/exclusion criteria.

Eligible participants will be studied on three separate days in a randomized, double-blind,
crossover fashion. On each testing day, patients will be given one dose of the study
medication (either pyridostigmine, galantamine or placebo pill), and then will have two tilt
table tests (a motorized table with a footboard that moves to an upright position): one with
the vagal stimulation and one with sham electrical stimulation. Heart rhythm, blood pressure
and the amount of fluid in the body (body impedance) will be monitored during studies. Blood
samples (up to a total of 2 tablespoons per study day) will also be collected. The order of
the study days and tilt tests will be decided at random, like the toss of a coin. Each study
day will last about 5 hours.

Inclusion Criteria:

- Female subjects of 18-45 years, with Postural Tachycardia Syndrome (POTS) as defined
by a heart rate increase ≥30 bpm from supine within 10 min of standing or head-up tilt
in the absence of orthostatic hypotension, with chronic symptoms (> 6 months), and in
the absence of other acute cause of orthostatic tachycardia.

- Subjects able and willing to provide informed consent

Exclusion Criteria:

- Pregnancy.

- Medical conditions that can explain postural tachycardia (e.g., dehydration,
medications).

- Patients who are bedridden or chair-ridden

- Subjects taking any medication known to affect autonomic function or inflammatory
markers (e.g. corticosteroids) who could not discontinue them before study
participation.

- Conditions associated with chronic inflammatory processes which in the investigator's
opinion would affect the interpretation of the results. Examples may include smoking,
diabetes, BMI>30 kg/m2, current infections or cancer.

- Other factors which in the investigator's opinion would prevent the subject from
completing the protocol.