Anticipatory Central Command on Standing Decreases Cerebral Blood Flow Causing Hypocapnia in Hyperpneic Postural Tachycardia Syndrome, 2023, Stewart

[voner]

Abstract

50% of POTS patients are hypocapnic during orthostasis related to initial orthostatic hypotension (iOH). We determined whether iOH drives hypocapnia in POTS by low BP or decreased cerebral blood flow velocity (CBFv). We studied 3 groups; healthy volunteers (N=32, 18±3y) were compared to POTS, grouped by presence (POTS-↓ETCO2, N=26, 19±2y) or absence (POTS-nlCO2, N=28, 19±3y) of standing hypocapnia defined by End Tidal CO2 (ETCO2) ≤30 mmHg at steady-state), measuring middle cerebral artery CBFv, heart rate (HR) and beat-to-beat blood pressure (BP). After 30 minutes supine, subjects stood for 5 minutes. Quantities were measured pre-standing, at minimum-CBFv, minimum-BP, peak-HR, CBFv-recovery, BP-recovery, minimum-HR, steady-state, and 5 min. Baroreflex gain was estimated by alpha index. iOH occurred with similar frequency and minimum-BP in POTS-↓ETCO2 and POTS-nlCO2. Minimum-CBFv was reduced significantly (p<0.05) in POTS-↓ETCO2 (48±3cm/s) preceding hypocapnia compared to POTS-nlCO2 (61±3cm/s)or Control(60±2cm/s). The anticipatory increased BP was significantly larger (p<0.05) in POTS (8±1 mmHg vs 2±1) and began ~8 seconds pre-standing. HR increased in all subjects, CBFv increased significantly (p<0.05) in both POTS-nlCO2 (76±2 to 85±2cm/s) and Control (75±2 to 80±2cm/s) consistent with Central Command. CBFv decreased in POTS-↓ETCO2 (76±3 to 64±3cm/s) correlating with decreased baroreflex gain. Cerebral conductance (meanCBFv/MAP) was reduced in POTS-↓ETCO2 throughout. Data support the hypothesis that excessively reduced CBFv during iOH may intermittently reduce carotid body blood flow, sensitizing that organ and producing postural hyperventilation in POTS-↓ETCO2. Excessive fall in CBFv occurs in part during pre-standing Central Command and is a facet of defective parasympathetic regulation in POTS.

paywall: https://journals.physiology.org/doi/abs/10.1152/japplphysiol.00016.2023?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org


The authors are Julian Stewart and Marvin Medow of New York Medical College.

 

[SNT Gatchaman]

We studied 3 groups; healthy volunteers (N=32, 18±3y) were compared to POTS, grouped by presence (POTS-↓ETCO2, N=26, 19±2y) or absence (POTS-nlCO2, N=28, 19±3y) of standing hypocapnia defined by End Tidal CO2 (ETCO2 ) ≤30 mmHg at steady-state), measuring middle cerebral artery CBv, heart rate (HR) and beat-to-beat blood pressure (BP).

Subjects stood up over <5 seconds and remained standing for 5 minutes while HR, BP, ETCO2 and [middle cerebral artery blood velocity] were continuously monitored. We explained the standing procedure to all study participants who were told that the research technician would approach the tilt table 5-10 seconds prior to standing. The act of approach provoked an anticipatory response comprising an increase in HR, and BP in all subjects, an increase in CBv in control subjects and POTS-nlCO 2 subjects, but a decrease in CBv in POTS-↓CO 2 subjects. Five minutes of standing was chosen because we have not observed vasovagal syncope within this time period, and 5 minutes sufficed to establish steady state HR. Some POTS patients fulfilled criteria for iOH during the standing procedure with brief OI symptoms. After 5 minutes, subjects returned to supine for recovery during which baseline HR, BP, ETCO2 , and CBv were restored.

Compare and contrast with Fear conditioning as a pathogenic mechanism in the postural tachycardia syndrome (2022).

 

[Peter T]

Hypocarbia or hypocapnia is a decrease in alveolar and blood carbon dioxide (CO2) levels below the normal reference range of 35 mmHg.