Faculty Collaboration Database

Chronic moderate hypercapnia suppresses ventilatory responses to acute CO<sub>2</sub> challenges. J Appl Physiol (1985) 2022 Nov 01;133(5):1106-1118

Date

09/23/2022

Pubmed ID

36135953

Pubmed Central ID

PMC9621709

DOI

10.1152/japplphysiol.00407.2022

Scopus ID

2-s2.0-85141003919 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

Chronic hypercapnia (CH) is a hallmark of chronic lung disease, and CH increases the risk for acute-on-chronic exacerbations leading to greater hypoxemia/hypercapnia and poor health outcomes. However, the role of hypercapnia per se (duration and severity) in determining an individual's ability to tolerate further hypercapnic exacerbations is unknown. Our primary objective herein was to test the hypothesis that mild-to-moderate CH (arterial [Formula: see text] ∼50-70 mmHg) increases susceptibility to pathophysiological responses to severe acute CO<sub>2</sub> challenges. Three groups (GR) of adult female goats were studied during 14 days of exposure to room air (<i>GR 1</i>; control) or 6% inspired CO<sub>2</sub> (<i>GR 2</i>; mild CH), or 7 days of 6% inspired CO<sub>2</sub> followed by 7 days of 8% inspired CO<sub>2</sub> (<i>GR 3</i>; moderate CH). Consistent with previous reports, there were no changes in physiological parameters in <i>GR 1</i> (RA control), but mild CH (<i>GR 2</i>) increased steady-state ventilation and transiently suppressed CO<sub>2</sub>/[H<sup>+</sup>] chemosensitivity. Further increasing InCO<sub>2</sub> from 6% to 8% (<i>GR 3</i>) transiently increased ventilation and arterial [H<sup>+</sup>]. Similar to mild CH, moderate CH increased ventilation to levels greater than predicted. However, in contrast to mild CH, acute ventilatory chemosensitivity was suppressed throughout the duration of moderate CH, and the arterial - mixed expired CO<sub>2</sub> gradient became negative. These data suggest that moderate CH limits physiological responses to acute severe exacerbations and provide evidence of recruitment of extrapulmonary systems (i.e., gastric CO<sub>2</sub> elimination) during times of moderate-severe hypercapnia.<b>NEW & NOTEWORTHY</b> Moderate levels of chronic hypercapnia (CH; ∼70 mmHg) in healthy adult female goats elicited similar steady-state physiological adaptations compared with mild CH (∼55 mmHg). However, unlike mild CH, moderate CH chronically suppressed acute CO<sub>2</sub>/[H<sup>+</sup>] chemosensitivity and reversed the arterial to mixed expired CO<sub>2</sub> gradient. These findings suggest that moderate CH suppresses vital mechanisms of ventilatory control and recruits additional physiological systems (i.e., gastric CO<sub>2</sub> release) to help buffer excess CO<sub>2</sub>.

Author List

Buchholz KJ, Neumueller SE, Burgraff NJ, 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

Animals
Carbon Dioxide
Female
Goats
Hypercapnia
Hypoxia
Respiration