LAUSR

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, severity) in determining an individual's ability to tolerate hypercapnic exacerbations is unknown. Our primary objective herein was to test the hypothesis that mild-to-moderate CH (PaCO2 ~50-70mmHg) increases susceptibility to pathophysiologic responses to severe acute CO2 challenges. Three groups (GR) of adult female goats were studied during 14d exposure to room air (GR1; control) or 6% inspired CO2 (GR2; mild CH), or 7d of 6% InCO2 followed by 7d of 8% InCO2 (GR3; moderate CH). Consistent with previous reports, mild CH led to transient increases in steady state ventilation, a transient suppression of CO2/[H+] chemosensitivity, and there were no changes in physiologic parameters in GR1 (control). Further increasing InCO2 from 6% to 8% also further increased steady state PaCO2 and ventilation to levels greater than predicted like that during mild CH. However, in contrast to mild CH acute ventilatory chemosensitivity was suppressed throughout the duration of moderate CH, and the arterial-mixed expired CO2 gradient became negative. These data suggest that moderate CH blunts physiological responses to acute severe exacerbations and provide evidence of recruitment of extra-pulmonary systems (i.e. gastric CO2 elimination) during times of moderate-severe hypercapnia.