Chemoreflex and Baroreflex Alterations Causing Postural Tachycardia Syndrome With Orthostatic Hyperpnea and Hypocapnia

Mechanism of Chemoreflex and Baroreflex Alterations Causing Postural Tachycardia Syndrome in POTS Patients With Orthostatic Hyperpnea and Hypocapnia

Postural tachycardia syndrome (POTS) is the most common chronic cause of postural lightheadedness, and upright confusion afflicting many Americans, mostly young women. Many POTS patients hyperventilate by increasing their depth of breathing that produces tachycardia, alters blood flow and blood pooling in the body and importantly reduces brain blood flow causing "brain fog". In this proposal the investigators will demonstrate in young women that abnormal repeated brief impairment of blood pressure and brain flow just after standing sensitizes the body's oxygen sensor in POTS to respond as if it were in a low oxygen environment causing hyperventilation and its consequences. In this project the investigators will use various drugs that will help to understand the mechanisms that cause POTS in this unique subset of POTS patients who hyperventilate.

The Investigators will compare results from female POTS patients, free of known pulmonary or sleep disorders aged 15 to 39 years with, and without orthostatic hyperpneic hypocapnia, to healthy female volunteers with the following two (2) specific aims:

1. To test poikilocapnic (allowing carbon dioxide (CO2) to vary) orthostatic cardiorespiratory responses to determine whether prolonged initial orthostatic hypotension (IOH) precedes upright hypocapnia in hyperpneic POTS but not in controls or non-hyperpneic POTS. Subjects are instrumented for cerebral blood flow, respiratory and hemodynamic measurements, investigating splanchnic blood flow by indocyanine green infusion, and measuring changes of CBV, regional blood volumes, and cardiac output (CO) by impedance plethysmography during a 10 min stand to quantify IOH, and a 10 min tilt test to 70⁰ to quantitate cardiorespiratory changes. These changes during tilt stratify hyperpneic and non-hyperpneic POTS.
2. To test if chemoreflex sensitization of ventilation and sympathetic activity (by microneurography) are abnormal when supine and tilted upright at 45o and how that interacts with Oxford measured cardiovagal and sympathetic baroreflexes under controlled gas conditions which are: isocapnic hypoxia and isocapnic hyperoxia to measure carotid body reflex; hyperoxic isocapnia and hyperoxic hypercapnia to measure central chemoreflexes. Hyperoxia silences peripheral chemoreceptors and will normalize baroreflex and tilt responses.

Inclusion Criteria:

• The investigators will recruit female POTS cases (N=80) and healthy female control subjects (N=40) aged 15-39 years, matched for BMI. POTS is a disease in which 80-90% are females. Therefore, the investigators will only recruit female POTS patients and controls.

Exclusion Criteria:

• Any subjects with systemic disease or who cannot stop taking prescribed medications for at least 2 weeks prior to study.