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Hypercapnic ventilatory chemoreflex sensitivity increases with exercise intensities up to the respiratory compensation point

2025· article· en· W4411879847 on OpenAlexaffabout
Nasimi A. Guluzade, Brad Matushewski, Daniel A. Keir

Bibliographic record

VenuePhysiology · 2025
Typearticle
Languageen
FieldMedicine
TopicHeart Rate Variability and Autonomic Control
Canadian institutionsWestern University
Fundersnot available
KeywordsRespiratory compensationHypercapniaSensitivity (control systems)Respiratory systemCompensation (psychology)RespirationMedicineAnesthesiaPhysical medicine and rehabilitationCardiologyNeuroscienceInternal medicinePsychologyPhysical therapyAnatomySocial psychologyEngineering

Abstract

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The hypercapnic ventilatory chemoreflex response (HCVR), a mechanism for maintaining arterial blood gas homeostasis during exercise, is known to increase from rest to exercise; however, it remains unclear whether this response becomes further sensitized with increasing intensities below the respiratory compensation point (RCP), a critical threshold in exercise physiology that delineates shifts in ventilatory control. Twenty-three healthy young participants (mean±SD: age=23±4 years, V˙O 2max =42.0±8.2 mL·kg -1 ·min -1 , 12 females) completed a maximal cycling exercise protocol (Visit 1) and three, repeated step-incremental protocols (Visits 2-4) over three days. The step-incremental protocol involved two, 8-min stages in the lower and upper regions of the moderate-intensity domain (MOD 1 and MOD 2 , i.e., below lactate threshold, LT) and two, 12-min stages within the heavy-intensity domain (HVY 1 and HVY 2 , i.e., between LT and RCP). Arterialized-venous blood samples were obtained from a dorsal hand vein catheter, with the hand warmed to ensure arterialization (Visit 2). At three time points during steady-state exercise at each intensity (Visits 3 and 4), hypercapnia was administered for ~20 s (6-8 breaths) by rebreathing from a bag containing 22% O 2 , 4% CO 2 and balanced N 2 . Throughout exercise, gas exchange and ventilatory variables were measured breath-by-breath by metabolic cart and pneumotach. At each intensity, HCVR was determined as the slope of the ventilation (V· E ) vs. end-tidal CO 2 pressure (P ET CO 2 ) relationship (V· E S, L·min -1 ·mmHg -1 ) from the average of the six repeated trials. One-way repeated measures analysis of variance investigated between-intensity differences in arterialized blood gas measures and HCVR. The average arterial [H + ] at MOD 1 was 39.5±1.5 nM and rose significantly (p<0.001) to 40.5±1.9, 41.5±2.4, and 42.7±3.1 nM at MOD 2 , HVY 1 , and HVY 2 , respectively whereas mean PaCO 2 decreased from 40.8±2.4 mmHg in MOD 1 to 40.6±2.7, 39.4±2.7, and 37.3±2.7 mmHg. At MOD 1 , the average V· E S was 2.4±0.9 L·min -1 ·mmHg -1 and increased with intensity (p<0.001) to 2.8±0.8, 3.3±0.9, and 3.8±1.7 L·min -1 ·mmHg -1 at MOD 2 , HVY 1 , and HVY 2 , respectively. The P ET O 2 was normoxic and did not change (p=0.200) with intensity (MOD 1 : P ET O 2 = 106±8 mmHg; MOD 2 : P ET O 2 = 104±7; HVY 1 : P ET O 2 = 103±8; HVY 2 : P ET O 2 = 105±8). HCVR progressively increased with higher steady-state exercise intensities suggesting that the peripheral chemoreflex is increasingly sensitized. Whether such sensitization is necessary to maintain arterial blood gas homeostasis during exercise up to RCP warrants further investigation. DAK: NSERC Discovery Grant (RGPIN-2021-03980) and by the Canadian Foundation for Innovation John Evans Leadership Fund (Project: 42544). NAG: OGS and NSERC CGS-D Award. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board 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 score0.923
Threshold uncertainty score0.345

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 head0.017
GPT teacher head0.273
Teacher spread0.256 · 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
Published2025
Admission routes2
Has abstractyes

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