Physiologic and neurochemical adaptations following abrupt termination of chronic hypercapnia in goats.

Chronic hypercapnia (CH) is a hallmark of respiratory diseases such as chronic obstructive pulmonary disease. In such patients, mechanical ventilation is often used to restore normal blood-gas homeostasis. However, little is known regarding physiologic changes and neuroplasticity within physiological control networks after termination of CH. Utilizing our goat model of increased inspired CO2-induced CH, we determined whether termination of CH elicits time-dependent physiologic and neurochemical changes within brainstem sites of physiologic control. Thirty days (d) of CH increased PaCO2 (+15mmHg) and steady-state ventilation (SS VI) (283% of control). Within 24 hours (h) after terminating CH, SS VI, blood gases, arterial [H+] and most physiologic measurements returned to control. However, the acute ventilatory chemoreflex (ΔVI/Δ[H+]) was greater than control, and measured SS VI exceeded ventilation predicted by arterial [H+] and ΔVI/Δ[H+]. Potentially contributing to these differences were increased excitatory neuromodulators serotonin and norepinephrine in the nucleus tractus solitarius, which contrasts to minimal changes observed at 24h and 30d of hypercapnia. Similarly, there were minimal changes found in markers of neuroinflammation and glutamate receptor-dependent neuroplasticity upon termination of CH, which were previously increased following 24h of hypercapnia. Thus, following termination of CH: 1) ventilatory, renal, and other physiologic functions rapidly return to control 2) neuroplasticity within the ventilatory control network may contribute to the difference between measured vs. predicted ventilation, and the elevation in the acute ventilatory [H+] chemoreflex, and 3) neuroplasticity is fundamentally distinct from acclimatization to CH.