Cardiovagal Baroreflex Deficits Impair Neurovascular Coupling and Cognition in POTS

Orthostatic intolerance is defined by debilitating upright symptoms that are relieved by
sitting or lying. Symptoms include upright lightheadedness, fatigue, confusion, and decreased
memory called 'Brain Fog' by patients. The most common chronic form is Postural Tachycardia
Syndrome (POTS), characterized by excessive upright tachycardia without hypotension. Of note,
>85% of POTS patients are female. The proposal that Brain Fog was caused by reduced cerebral
blood flow (CBF) has been disproven, because graded incremental upright tilt failed to
demonstrate difference in mean CBF compared to healthy volunteers. Nevertheless, memory task
performance deteriorates with angle of tilt as does task-related neurovascular coupling
(NVC), which links neural activity to an increase in CBF known as "functional hyperemia". The
investigators have previously observed that large low frequency (0.07-0.13 Hz) oscillations
in BP (OBP), which entrained and amplified oscillations in CBF (OCBF), increased with tilt
angle and were associated with impaired working memory and reduced functional hyperemia.

The sympathetic baroreflex remains intact and HR is excessively increased in the absence of
parasympathetic counterregulation. The cardiovagal baroreflex couples BP to HR to buffer BP
changes. Large low frequency BP oscillations, representing a resonance within the sympathetic
baroreflex loop, occur if there is central hypovolemia, an intact sympathetic baroreflex, and
reduced parasympathetic buffering of BP by HR; conditions found in upright POTS. This leads
to the following hypothetical paradigm:

↓Cardiovagal Baroreflex → ↑OBP → ↑↑OCBF → ↓NVC → ↓working memory. Therefore, in this
application, the investigators hypothesize that the cardiovagal baroreflex is impaired in
POTS while supine, becomes further impaired with orthostasis, and accounts for OBP, OCBF, and
loss of NVC. Further, the investigators propose that improving the cardiovagal baroreflex
improves hemodynamics and Brain Fog in POTS patients.

Inclusion Criteria for POTS patients:

POTS patients referred for day to day orthostatic intolerance with greater than 3 symptoms
for greater than 3 months and will have the diagnosis of symptomatic postural tachycardia
made during a screening tilt table test :

- dizziness

- nausea and vomiting

- palpitations

- fatigue

- headache

- exercise intolerance

- blurred vision

- abnormal sweating heat.

Healthy control subjects:

- normal physical examination, and normal electrocardiographic and echocardiographic
evaluations.

- Only those free from heart disease, and from systemic illness will be eligible to
participate.

- This excludes patients with illnesses and disease states known to be associated with
endothelial cell dysfunction such as diabetes, renal disease, congestive heart
failure, systemic hypertension, acute and chronic inflammatory diseases, neoplasm,
immune mediated disease, trauma, morbid obesity and peripheral vascular disease.

At the time of testing all patients and control subjects must refrain from vasoactive drugs
for two weeks.

Exclusion Criteria for both POTS and healthy controls:

- An active medical condition that may explain the diagnosis

- A previous medical condition with undocumented resolution that may explain the
diagnosis

- any systemic or overt structural, arrhythmic or myopathic cardiovascular disease

- any illnesses known to produce autonomic dysfunction such as diabetes, heart disease,
renal disease, systemic hypertension, acute and chronic inflammatory diseases,
neoplastic disease, immune mediated disease, major trauma and burns, morbid obesity
and peripheral vascular disease will also be excluded.

- Cigarette smokers will be excluded.

- Past or present major psychiatric disorder

- Substance abuse within 2 years before onset of symptoms.