Physiol Rep
Department of Biology, Faculty of Science and Technology, Mount Royal University, Calgary, Alberta, Canada.
Published: December 2022
Ventilatory acclimatization (VA) is important to maintain adequate oxygenation with ascent to high altitude (HA). Transient hypoxic ventilatory response tests lack feasibility and fail to capture the integrated steady-state responses to chronic hypoxic exposure in HA fieldwork. We recently characterized a novel index of steady-state respiratory chemoreflex drive (SSCD), accounting for integrated contributions from central and peripheral respiratory chemoreceptors during steady-state breathing at prevailing chemostimuli. Acetazolamide is often utilized during ascent for prevention or treatment of altitude-related illnesses, eliciting metabolic acidosis and stimulating respiratory chemoreceptors. To determine if SSCD reflects VA during ascent to HA, we characterized SSCD in 25 lowlanders during incremental ascent to 4240 m over 7 days. We subsequently compared two separate subgroups: no acetazolamide (NAz; n = 14) and those taking an oral prophylactic dose of acetazolamide (Az; 125 mg BID; n = 11). At 1130/1400 m (day zero) and 4240 m (day seven), steady-state measurements of resting ventilation (V̇ ; L/min), pressure of end-tidal (P )CO (Torr), and peripheral oxygen saturation (SpO ; %) were measured. A stimulus index (SI; P CO /SpO ) was calculated, and SSCD was calculated by indexing V̇ against SI. We found that (a) both V̇ and SSCD increased with ascent to 4240 m (day seven; V̇ : +39%, p < 0.0001, Hedges' g = 1.52; SSCD: +56.%, p < 0.0001, Hedges' g = 1.65), (b) and these responses were larger in the Az versus NAz subgroup (V̇ : p = 0.02, Hedges' g = 1.04; SSCD: p = 0.02, Hedges' g = 1.05). The SSCD metric may have utility in assessing VA during prolonged stays at altitude, providing a feasible alternative to transient chemoreflex tests.
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http://dx.doi.org/10.14814/phy2.15521 | DOI Listing |
J Neurosci
January 2025
Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908
The homeostatic regulation of pulmonary ventilation, and ultimately arterial PCO, depends on interactions between respiratory chemoreflexes and arousal state. The ventilatory response to CO is triggered by neurons in the retrotrapezoid nucleus (RTN) that function as sensors of central pH, which can be identified in adulthood by the expression of Phox2b and neuromedin B. Here, we examine the dynamic response of genetically defined RTN neurons to hypercapnia and arousal state in freely behaving adult male and female mice using the calcium indicator jGCaMP7 and fiber photometry.
View Article and Find Full Text PDFSleep Med
December 2024
Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address:
J Neurophysiol
November 2024
Macquarie Medical School, Faculty of Medicine, Health and Human SciencesMacquarie University, Sydney, Australia.
J Clin Sleep Med
December 2024
Merck & Co., Inc., Rahway, New Jersey.
Study Objectives: Obstructive sleep apnea (OSA) is a highly prevalent disorder with serious health consequences but limited therapeutic options. For a subset of those with OSA, a key underlying mechanism is hypersensitive chemoreflex control of breathing. There is no approved therapy that targets this endotypic trait.
View Article and Find Full Text PDFJ Appl Physiol (1985)
August 2024
Division of Biomedical Sciences, School of MedicineUniversity of California, Riverside, California, United States.
Ventilatory responses to hypoxia and hypercapnia play a vital role in maintaining gas exchange homeostasis and in adaptation to high-altitude environments. This study investigates the mechanisms underlying sensitization of hypoxic and hypercapnic ventilatory response (HVR and HCVR, respectively) in individuals acclimatized to moderate high altitude (3,800 m). Thirty-one participants underwent chemoreflex testing using the Duffin-modified rebreathing technique.
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