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Postural hyperventilation in POTS is not driven by exaggerated peripheral chemoreceptor activity

2023· article· en· W4378675023 on OpenAlexaff
Jacquie Baker, Anthony V. Incognito, Shaun Ranada, Aaron A. Phillips, Robert S. Sheldon, Richard J. A. Wilson, Satish R. Raj

Bibliographic record

VenuePhysiology · 2023
Typearticle
Languageen
FieldMedicine
TopicCardiovascular Syncope and Autonomic Disorders
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsHypocapniaHyperventilationMedicineSupine positionAnesthesiaHeart rateVentilation (architecture)Orthostatic vital signsRespiratory minute volumeHyperoxiaOrthostatic intoleranceBlood pressureCardiologyInternal medicineHypercapniaRespiratory systemLungAcidosis

Abstract

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BACKGROUND: Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic form of autonomic nervous system dysfunction primarily affecting premenopausal females. POTS patients experience chronic orthostatic symptoms, and a heart rate (HR) increase of ≥30 bpm within 10 min of standing in the absence of orthostatic hypotension (>20/10 mmHg decrease in blood pressure [BP]). On standing, patients can exhibit increased ventilation (V E ) with subsequent reductions in end-tidal CO2 (i.e., hypocapnia). Hypocapnia exacerbates tachycardia and symptoms. Previous research has suggested exaggerated peripheral chemoreceptor (pChR) activity drives postural hyperventilation in POTS. OBJECTIVE: We explored exaggerated pChR activity in the pathophysiology of postural hyperventilation in POTS. HYPOTHESIS: We hypothesized that POTS patients have a greater V E reduction during pChR inhibition compared to healthy controls. METHODS: We conducted a randomized crossover trial of hyperoxia vs. normoxia while supine and during head-up tilt (HUT) in 25 POTS patients (F=25; age: 31±8 years) and 12 healthy controls (HC) (F=12; age: 31±6 years; p=0.8). To inhibit pChR, participants breathed 5x30sec bouts of normocapnic hyperoxia (O 2 : ~400mmHg). Continuous respiratory (V E , ETO 2 , ETCO 2 ) and hemodynamics (HR, BP, stroke volume, cardiac output, systemic vascular resistance) were measured. Data are reported as mean±SD. Continuous variables were compared using a 3-factor mixed-effects model: [Group: Control vs. Patient] x [Position (repeated measure): supine vs. HUT] x [Gas (repeated measure): ON vs. OFF). RESULTS During normoxic HUT, V E increased relative to supine baseline in both POTS (Supine: 10.3±2.3 L/min, HUT: 15.2±4.2; p<0.001) and HC (Supine: 11.1±2.1 L/min, HUT: 12.9±2.3 L/min; p=0.04). As predicted, the ΔV E in response to HUT was significantly greater in POTS (4.8±3.3 L/min) vs. HC (1.8±1.6 L/min; p=0.001). During HUT, hyperoxia reduced V E in both POTS (p<0.001) and HC (p<0.001). However, the magnitude of the ventilatory inhibition was not different between groups (POTS: -1.9±1.0 L/min; HC: -1.8±1.0 L/min; p=1.0). CONCLUSION: POTS patients have increased postural V E relative to HC. During pChR inhibition with hyperoxia, V E was reduced in both HC and POTS, and the magnitude of ventilatory inhibition in response to hyperoxia was the same in both groups. These findings suggest pChR activity is not exaggerated in POTS patients, and thus is not the primary driver of postural hyperventilation observed in POTS. This work was supported by Standing up to POTS. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.955
Threshold uncertainty score0.415

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.016
GPT teacher head0.269
Teacher spread0.252 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2023
Admission routes1
Has abstractyes

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