Ventilatory acclimatization to hypoxia is not dependent on cerebral hypocapnic alkalosis

Abstract

We previously demonstrated that, in awake goats, 6 h of hypoxic carotid body perfusion during systemic normoxia produced time-dependent hyperventilation that is typical of ventilatory acclimatization to hypoxia (VAH). The hypocapnic alkalosis that occurred could have produced VAH by inducing cerebral vasoconstriction and brain lactic acidosis even though systemic arterial normoxia was maintained. In the present study we tested the hypothesis that hypocapnic alkalosis is a necessary component of VAH. Goats were prepared so that one carotid body could be perfused, from an extracorporeal circuit, with blood in which gas tensions could be controlled independently from the blood perfusing the systemic arterial system, including the brain. Using this preparation we carried out 4 h of hypoxic carotid body perfusion while maintaining systemic arterial (and brain) normoxia in awake goats. Expired minute ventilation (VE) was measured while CO2 was added to inspired air to maintain normocapnia. Carotid body PCO2 and PO2 were maintained near 40 Torr during the 4-h carotid body perfusion. Control mean VE was 8.65 +/- 0.48 l/min (mean +/- SE). With acute carotid body hypoxia (30 min) VE increased to 21.73 +/- 2.02 l/min (P less than 0.05); over the ensuing 3.5 h of carotid body hypoxia, VE progressively increased to 39.14 +/- 4.14 l/min (P less than 0.05). These data indicate that neither cerebral hypoxia nor hypocapnic alkalosis are required to produce VAH. After termination of the 4-h carotid body stimulation, hyperventilation was not maintained in these studies, i.e., there was no deacclimatization. This suggests that acclimatization and deacclimatization are produced by different mechanisms.

Impact of intermittent hypoxia on long-term facilitation of minute ventilation and heart rate variability in men and women: do sex differences exist?

“…The ⌬V E/⌬PET O 2 is considered by many investigators to be indicative of peripheral chemoreflex sensitivity (8,9,44). Accordingly, our findings might suggest that chemoreflex sensitivity was decreasing from the initial to the final hypoxic episode.…”

The influence of chronic hypoxia upon chemoreception

“…Six hours of isolated carotid body hypoxia caused a progressive increase in ventilation above the acute hypoxic ventilatory response (Busch et al, 1985). Such time-dependent changes in ventilation did not occur with (a) 6 hours of carotid body hypercapnia (Bisgard et al, 1986a), (b) 4 hr of systemic hypocapnia (Bisgard et al, 1986b) or, (c) systemic arterial hypoxia (Weizhen et al, 1992). These results show the response is specific to carotid body hypoxia and not the result of increased carotid body stimulation or activity, or changes in P O 2 or pH at central chemoreceptors and respiratory centers in the brain.…”

Increase in Carotid Body Sensitivity during Sustained Hypoxia

“…It was first shown that 4-6 h of steady-state hypoxic CB perfusion (Po2 = 40 Torr) during systemic normoxia (brain normoxia) could produce time-dependent hyperventilation that is indistinguishable from that produced by systemic hypoxia in awake goats [16][17][18]. Thus, ventilatory acclimatization could be in duced in the absence of brain hypoxia and stimulation of the CB alone could induce acclimatization.…”