Baroreceptor unloading in postural tachycardia syndrome augments peripheral chemoreceptor sensitivity and decreases central chemoreceptor sensitivity

Abstract

While orthostatic tachycardia is the hallmark of postural tachycardia syndrome (POTS), orthostasis also initiates increased minute ventilation (Ve) and decreased end-tidal CO(2) in many patients. We hypothesized that chemoreflex sensitivity would be increased in patients with POTS. We therefore measured chemoreceptor sensitivity in 20 POTS (16 women and 4 men) and 14 healthy controls (10 women and 4 men), 16-35 yr old by exposing them to eucapneic hyperoxia (30% O(2)), eucapneic hypoxia (10% O(2)), and hypercapnic hyperoxia (30% O(2) + 5% CO(2)) while supine and during 70° head-upright tilt. Heart rate, mean arterial pressure, O(2) saturation, end-tidal CO(2), and Ve were measured. Peripheral chemoreflex sensitivity was calculated as the difference in Ve during hypoxia compared with room air divided by the change in O(2) saturation. Central chemoreflex sensitivity was determined by the difference in Ve during hypercapnia divided by the change in CO(2). POTS subjects had an increased peripheral chemoreflex sensitivity (in l·min(-1)·%oxygen(-1)) in response to hypoxia (0.42 ± 0.38 vs. 0.19 ± 0.17) but a decreased central chemoreflex sensitivity (l·min(-1)·Torr(-1)) CO(2) response (0.49 ± 0.38 vs. 1.04 ± 0.18) compared with controls. CO(2) sensitivity was also reduced in POTS subjects when supine. POTS patients are markedly sensitized to hypoxia when upright but desensitized to CO(2) while upright or supine. The interactions between orthostatic baroreflex unloading and altered chemoreflex sensitivities may explain the hyperventilation in POTS patients.

Reduced Cerebral Blood Flow With Orthostasis Precedes Hypocapnic Hyperpnea, Sympathetic Activation, and Postural Tachycardia Syndrome

“…A decreased chemoreflex response to CO 2 and increased hypoxic ventilatory response found in POTS subjects 6 contributes to hyperventilation. CBF derives largely from carotid artery blood flow.…”

“…Some with OI complain of dyspnea associated with hyperventilation and hypocapnia 4-6 . Thus, neurogenic orthostatic hypotension and vasovagal syncope are frequently associated with hyperventilation.…”

“…We previously attributed hyperventilation to splanchnic hyperemia resulting in thoracic hypovolemia, baroreflex unloading and consequent sympathoexcitation and activation of respiratory centers 3 . In addition, hyperventilation is facilitated by enhanced hypoxic and reduced hypercapnic ventilatory responses in POTS due to altered peripheral and central chemoreceptor sensitivity 6 . Hyperventilation produces large reductions in cerebral blood flow (CBF) 15 and neuronal ischemia.…”

Postural Hyperventilation as a Cause of Postural Tachycardia Syndrome: Increased Systemic Vascular Resistance and Decreased Cardiac Output When Upright in All Postural Tachycardia Syndrome Variants

“…POTS was identified during tilt table testing by signs and symptoms of OI and an excessive increase in HR without hypotension within 10 minutes of head‐up tilt 4, 24, 25. Excessive tachycardia is defined in adolescents by an increase in HR of at least 40 beats per minute or an HR >120 beats per minute in the absence of postural hypotension and defined in patients >19 years by an HR increase of 30 beats per minute, during a 10‐minute upright tilt table test 3, 6. Other medical problems that could explain these signs or symptoms had been ruled out.…”

“…Dyspnea, hyperventilation, and hypocapnia have been reported in association with POTS and also in other forms of OI, including neurogenic orthostatic hypotension and vasovagal syncope 6, 7, 8. Circulatory collapse9 and milder perturbations, such as induction of hypotension in healthy volunteers, result in hyperventilation and hypocapnia 10, 11.…”