# Quantifying ventilatory control with 3% CO2 inhalation during exercise

**Authors:** Suhaib M. Hashem, Stanley M. Yamashiro, Takahide Kato, Takaaki Matsumoto, Vasilis Z. Marmarelis

PMC · DOI: 10.3389/fphys.2025.1528519 · Frontiers in Physiology · 2025-04-25

## TL;DR

This study explores how breathing in 3% CO2 affects ventilation control during exercise by analyzing the roles of central and peripheral chemoreceptors.

## Contribution

The study introduces a novel method using a one input–one output model and Laguerre expansion to quantify central and peripheral chemoreflex mechanisms during CO2 inhalation.

## Key findings

- 3% CO2 inhalation significantly increased high frequency weighted gain averages (WGAs) at rest and during exercise except heavy exercise.
- Low frequency WGAs remained significant only during rest and baseline exercise.
- Changes in WGAs can be used as quantitative estimates of central and peripheral chemoreflexes.

## Abstract

CO2 mediated ventilation is mainly controlled by two homeostatic mechanisms. The central chemoreceptors are slower mechanisms that focus on blood pH sensing in the brain stem while the peripheral chemoreceptors are quicker to respond and reside in the carotid bodies. Quantification of these mechanisms in humans remain debated.

To quantify the impact that the central and peripheral chemoreceptors have on ventilation in response to changes in PETCO2 during exercise with normoxic breathing and 3% CO2 inhalation.

Six healthy males participated in a 5-stage bike protocol with and without 3% CO2 inhalation. We analyzed the time series data of their breath-by-breath PETCO2 and ventilation and generated a one input–one output model via the Laguerre expansion technique (LET) to construct the gain function and quantify the low (0.002–0.029 Hz) and high (0.03–0.15 Hz) frequency components using the weighted gain averages (WGA) as estimators of central and peripheral chemoreflex mechanisms respectively.

3% CO2 inhalation caused a significant increase the high frequency WGAs at rest and in all levels of exercise except heavy exercise. The low frequency WGAs, however, only maintain significance during rest and the baseline session of exercise.

Changes in WGA can be used as quantitative estimates of central and peripheral chemoreflexes. 3% CO2 activates both reflexes and is more apparent in the higher frequency WGAs during exercise due to the oxygen dependent mechanisms effects of exercise.

## Linked entities

- **Chemicals:** CO2 (PubChem CID 280)

## Full-text entities

- **Chemicals:** oxygen (MESH:D010100), PETCO2 (-), CO2 (MESH:D002245)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12061692/full.md

## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12061692/full.md

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Source: https://tomesphere.com/paper/PMC12061692