Postural hypocapnic hyperventilation is associated with enhanced peripheral vasoconstriction in postural tachycardia syndrome with normal supine blood flow

Abstract

Previous investigations have demonstrated a subset of postural tachycardia syndrome (POTS) patients characterized by normal peripheral resistance and blood volume while supine but thoracic hypovolemia and splanchnic blood pooling while upright secondary to splanchnic hyperemia. Such "normal-flow" POTS patients often demonstrate hypocapnia during orthostatic stress. We studied 20 POTS patients (14-23 yr of age) and compared them with 10 comparably aged healthy volunteers. We measured changes in heart rate, blood pressure, heart rate and blood pressure variability, arm and leg strain-gauge occlusion plethysmography, respiratory impedance plethysmography calibrated against pneumotachography, end-tidal partial pressure of carbon dioxide (Pet(CO2)), and impedance plethysmographic indexes of blood volume and blood flow within the thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations while supine and during upright tilt to 70 degrees. Ten POTS patients demonstrated significant hyperventilation and hypocapnia (POTS(HC)) while 10 were normocapnic with minimal increase in postural ventilation, comparable to control. While relative splanchnic hypervolemia and hyperemia occurred in both POTS groups compared with controls, marked enhancement in peripheral vasoconstriction occurred only in POTS(HC) and was related to thoracic blood flow. Variability indexes suggested enhanced sympathetic activation in POTS(HC) compared with other subjects. The data suggest enhanced cardiac and peripheral sympathetic excitation in POTS(HC).

Fig. 1

Spontaneous (left) and voluntary (right) hypocapnia brought about in a postural tachycardia syndrome (POTS) patient (left) and by voluntary hyperventilation (HV) in a healthy control subject (right), respectively. Voluntary hyperventilation was achieved by having the subject take a breath every 6 s and to breathe as deeply as possible. Such breathing was maintained for 3.5 min and stopped because of lightheadedness. End-tidal partial pressure of carbon dioxide (Pet_CO2), Respitrace volumes (Resp), and thoracic blood volumes (TBV) are shown from top to bottom. Upright tilt was associated with an increase in thoracic blood volume. Onset of hypocapnic hyperventilation was not related to an increase in thoracic blood volume.

Fig. 2

Construction of a time-integrated tidal volume curve (bottom) from the record of time-dependent relative Respitrace tidal volume (top). An intermediate step is to obtain the absolute value of the tidal volume curve (middle).

Fig. 3

Pet_CO2 (top), Respitrace tidal volume record (middle), and calculation of relative respiratory minute volume (bottom) as the slope of linear portions of the integrated tidal volume corresponding to times preceding and during upright tilt in a hypocapnic POTS (POTS_HC) patient.

Fig. 4

Changes in heart rate (top) and mean arterial pressure (MAP; bottom) during upright tilt. Heart rate increased in all subjects and was most increased in normocapnic POTS (POTS_NC) and next most in POTS_HC compared with control subjects. MAP is increased similarly for all subjects. *P < 0.05 vs. control. †P < 0.05 compared with POTS_NC.

Fig. 5

Changes in Pet_CO2 (top) and minute ventilation (bottom) during upright tilt. Pet_CO2 was decreased in all subjects but most markedly in POTS_HC patients. This was associated with enhanced minute ventilation in these same subjects. *P < 0.05 compared with control.

Fig. 6

Percent change in minute volume compared with percent change in Pet_CO2. Individual data are shown for each patient. Pet_CO2 is decreased in most patients but is most markedly decreased in POTS_HC patients in association with a marked increase in minute ventilation.

Fig. 7

Changes in total heart rate (HR) variability (top left), low frequency (LF)-to-high frequency (HF) ratio (bottom left), baroreflex gain (top right), and systolic blood pressure (BP) variability (bottom right) during upright tilt. HR variability and baroreflex gain decreases for all subjects, but most for POTS_HC patients. LF-to-HF ratio and BP variability increase for all subjects, but most for POTS_HC patients. *P < 0.05 compared with control.

Fig. 8

Percent changes in thoracic, splanchnic, pelvic, leg, and arm blood flows (top) and corresponding changes in segmental blood volumes (except arm; bottom) during upright tilt averaged over all subjects within a subject group. Thoracic blood flow was most reduced in POTS_NC subjects. Splanchnic flow was reduced in control subjects, but this was most blunted in POTS_HC. This was associated with a significant decrease in peripheral blood flow in these patients. *P < 0.05 compared with control.