Physiological 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 physiological changes and neuroplasticity within physiological control networks after termination of CH. Utilizing our goat model of increased inspired CO-induced CH, we determined whether termination of CH elicits time-dependent physiological and neurochemical changes within brain stem sites of physiological control. Thirty days of CH increased [Formula: see text] (+15 mmHg) and steady-state ventilation (SS V̇i; 283% of control). Within 24 h after terminating CH, SS V̇i, blood gases, arterial [H], and most physiological measurements returned to control. However, the acute ventilatory chemoreflex (ΔV̇i/Δ[H]) was greater than control, and measured SS V̇i exceeded ventilation predicted by arterial [H] and ΔV̇i/Δ[H]. Potentially contributing to these differences were increased excitatory neuromodulators serotonin and norepinephrine in the nucleus tractus solitarius, which contrasts with minimal changes observed at 24 h and 30 days 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 24 h of hypercapnia. Thus, following termination of CH: ) ventilatory, renal, and other physiological functions rapidly return to control; ) 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 ) neuroplasticity is fundamentally distinct from acclimatization to CH. In healthy adult goats, steady-state ventilation and most physiological measures return to control within 24 h after termination of chronic hypercapnia (CH). However, the acute [H] chemoreflex is increased, and measured ventilation exceeds predicted ventilation. At 24 h of recovery, excitatory neuromodulators are above control, but other measured markers of neuroplasticity are unchanged from control. Our data suggest that CH elicits persistent physiological and neurochemical changes for up to 24 h after termination of CH.