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

Summary

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.

Conditions

• Postural Orthostatic Tachycardia Syndrome
• Hypocapnia
• Hyperventilation

Interventions

DIAGNOSTIC_TEST

Chemoreflex Testing

The carotid body chemoreflex can be tested by holding carbon dioxide (CO2) constant (isocapnic) and applying hypoxia and hyperoxia. Measurements are then made of expiratory minute volume and of sympathetic activity. The central chemoreflex measures isocapnic and hypercapnic responses in the presence of hyperoxia to suppress the carotid body chemoreflex.

DIAGNOSTIC_TEST

Baroreflex testing

Baroreceptors are measured by the change of heart rate (HR) and sympathetic activity with changing blood pressure using the modified Oxford technique. Blood pressure is lowered an amount by a bolus of sodium nitroprusside and then raised by a bolus of phenylephrine. When standing baroreflexes are activated and the investigators will measure chemoreflex activity upright to see how baroreflex effects the chemoreflexes. Similarly chemoreflexes affect the baroreflexes best observed when the patients are supine.

DIAGNOSTIC_TEST

Orthostatic stress testing

Orthostatic Stress tests are administered in two forms: a standing test to evoke the initial orthostatic hypotensive response that sensitizes and triggers the carotid body chemoreflex by intermittent stagnant ischemia. And the 70 degree upright tilt test that best identifies causal changes in regional blood volumes and flows and in respiratory patterns of hyperpneic hypocapnia.

Sponsors & Collaborators

• New York Medical College

  lead OTHER

Principal Investigators

• Marvin S Medow, Ph.D. · New York Medical College

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

15 Years

Max Age

39 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-09-23

Primary Completion

2023-08-31

Completion

2024-08-31

Countries

• United States

Study Locations