Ventilatory, Arterial Blood Gas, pH, and Electrolyte Adaptations to Chronic Hypercapnia in Healthy Goats

Abstract

Respiratory diseases, such as chronic obstructive pulmonary disease (COPD), affect ~24 million U.S adults and cost $49B annually. Many of these patients hypoventilate, leading to chronic hypercapnia, cognitive dysfunction, and high mortality rates. To gain insight into hypercapnia induced changes in neural and physiological function, we studied the breathing, arterial blood gases, pH, electrolytes, and cognitive function in goats during 30 days of chronic hypercapnia (inspired CO2 (InCO2) of 6%) or normocapnia. PaCO2 increased 10 mmHg during the first day of hypercapnia, continued to rise to a maximum of 16 mmHg above control between days 11–12, and remained near this level thereafter. PaO2 remained ~20 mmHg above control throughout the exposure to hypercapnia. Minute ventilation increased by 319% above control on day 1 of hypercapnia (n=7), but declined to 249% above control by day 2 of hypercapnia (n=7). Thereafter, ventilation progressively decreased to a nadir around day 12 at 211% above control (n=6) and remained near this level for the remainder of CO2 exposure. The initial hyperpnea during hypercapnic exposure was due to increases in both tidal volume and breathing frequency. However, breathing frequency returned to near control levels during the first week of hypercapnia, while tidal volume remained elevated. Arterial blood was acidic (−0.05) during day 1 of hypercapnia, followed by a partial compensation by day 8 due to increased arterial [HCO3+] (+7.4 mEq/L). VI/PaCO2 and VI/H+ at 6% InCO2 initially increased ~250% above control and remained elevated for the duration of hypercapnic exposure. Arterial [Cl−] decreased ~4 mmol/L during the first day of CO2 exposure and remained below control (−4–5 mmol/L) for the remainder of the 30 days. Arterial [K+] increased ~0.5 mmol/L during the first week of hypercapnia, and remained above control. No changes were found in arterial [Na+] or [Ca2+]. Accuracy of shape selection (index of cognitive function) decreased nearly 50% during hypercapnia. There were no apparent changes in any physiologic measurement for up to 30 days in goats maintained in room air conditions. In conclusion, we have established a model for future study of neuroadaptive responses, that potentially underlie compromised phenotypic/cognitive function, in COPD patients.Support or Funding InformationDepartment of Veterans Affairs; NIH HL007852This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.