Faculty Collaboration Database

Ventilatory and integrated physiological responses to chronic hypercapnia in goats. J Physiol 2018 Nov;596(22):5343-5363

Date

09/14/2018

Pubmed ID

30211447

Pubmed Central ID

PMC6235946

DOI

10.1113/JP276666

Scopus ID

2-s2.0-85054917792 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

KEY POINTS: Chronic hypercapnia per se has distinct effects on the mechanisms regulating steady-state ventilation and the CO₂ /H⁺ chemoreflex. Chronic hypercapnia leads to sustained hyperpnoea that exceeds predicted ventilation based upon the CO₂ /H⁺ chemoreflex. There is an integrative ventilatory, cardiovascular and metabolic physiological response to chronic hypercapnia. Chronic hypercapnia leads to deterioration of cognitive function.

ABSTRACT: Respiratory diseases such as chronic obstructive pulmonary disease (COPD) often lead to chronic hypercapnia which may exacerbate progression of the disease, increase risk of mortality and contribute to comorbidities such as cognitive dysfunction. Determining the contribution of hypercapnia per se to adaptations in ventilation and cognitive dysfunction within this patient population is complicated by the presence of multiple comorbidities. Herein, we sought to determine the role of chronic hypercapnia per se on the temporal pattern of ventilation and the ventilatory CO₂ /H⁺ chemoreflex by exposing healthy goats to either room air or an elevated inspired CO₂ (InCO₂ ) of 6% for 30 days. A second objective was to determine whether chronic hypercapnia per se contributes to cognitive dysfunction. During 30 days of exposure to 6% InCO₂ , steady-state (SS) ventilation ( V̇_I ) initially increased to 335% of control, and then within 1-5 days decreased and stabilized at ∼230% of control. There was an initial respiratory acidosis that was partially mitigated over time due to increased arterial [HCO₃^- ]. There was a transient decrease in the ventilatory CO₂ /H⁺ chemoreflex, followed by return to pre-exposure levels. The SS V̇_I during chronic hypercapnia was greater than predicted from the acute CO₂ /H⁺ chemoreflex, suggesting separate mechanisms regulating SS V̇_I and the chemoreflex. Finally, as assessed by a shape discrimination test, we found a sustained decrease in cognitive function during chronic hypercapnia. We conclude that chronic hypercapnia per se results in: (1) a disconnect between SS V̇_I and the CO₂ /H⁺ chemoreflex, and (2) deterioration of cognitive function.

Author List

Burgraff NJ, Neumueller SE, Buchholz K, Langer TM 3rd, Hodges MR, Pan L, Forster HV

Author

Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adaptation, Physiological
Animals
Carbon Dioxide
Cognition
Female
Goats
Hypercapnia
Reflex
Respiration
Respiratory Mechanics