Role of Cerebrospinal Fluid [H+] in Ventilatory Deacclimatization from Chronic Hypoxia

Abstract

A B S T R A C T Once ventilatory acclinmatizationi beginsin sea level residents sojourning at high altitude, abrupt restoration of normal oxygen tensions will not restore ventilation to normal. We have investigated the role of cerebrospinal fluid (CSF) [He] in this sustained hyperventilation by measurinig CSF acid-base status in seven imien (lumbar) and five ponies (cisterinal) in normoxia, first at sea level anid then periodically over 13-24 h of"deacclimatization" after 3-5 d in hypoxia (PB = 440 mm Hg). After 1 h deaccliimcatization, hyperventilation continued at a level only slightly less than that obtained in chronic hypoxia (+ 1-2 mm Hg PA,O2), whereas CSF pH was either e(lual (in man) or alkaline (in pony, +0.02, P < 0.01) to sea level values. Between 1 and 12-13 h deacclimatization in all humans and ponies VA fell progressively (PA(,0( increased 4-7 mm Hg) and CSF pH became increasingly more acid (-0.02 to -0.05, P < 0.01). Between 12 acnd 24 h of normoxic deacclimatization in ponies, PAco, rose further toward norinal, coincideint with an increasing acidity in CSF (-0.02 pH). Similar negative correlations were found between changes in arterial pH and VA throughout normoxic deaccliimiatization. We conclude that [H+] in the lumbar or cisternal CSF is not the mediator of the continued hyperventilation and its gradual dissipation with time during normoxic deacclimatization from chronic hypoxia. These negative relationships of VA to CSF [H+] in normoxia are analogous to those previously shown during acclimatization to hypoxia.

Control of Breathing at High Altitude

“…A number of elegant studies which use specific perfusion of the brain or carotid bodies have demonstrated brain hypoxia or hypocapnia does not result in acclimatization, whereas perfusion of the carotid bodies alone with hypoxic blood, while main taining normoxic perfusion to the body and brain, does [34][35][36], Persistent hyperventilation during deacclimatization has been well documented [31,[37][38][39] (fig. 3).…”

“…3). In one such study [39] looking at the potential mechanism to this phe- nomenon, humans exposed to hypobaric hypoxia equiva lent to 4,300 m for 7 days continued to hyperventilate upon descent. NMR spectroscopy showed no change in intracellular pH in the cortex of the brain which suggests either the presence of another mediator or another site where the augmented sensitivity has developed.…”

Hypoxic ventilatory response is correlated with increased submaximal exercise ventilation after live high, train low

“…that continued hyperventilation upon removal of a hypoxic stimulus required chronic hypocapnia during acclimatisation (Engwall and Bisgard 1990). Only one study has investigated hyperventilation upon return to normoxia following the early stage of ventilatory acclimatisation in humans (Dempsey et al 1979). In that study, when subjects were returned to sea level after 3-5 days acclimatisation at 4,300 m altitude, resting _ V E remained elevated for up to 24 h. Therefore, it appears that only several days of hypoxic acclimatisation may be required to produce hyperventilation upon return to normoxia.…”

Exposure to cyclic intermittent hypoxia increases expression of functional NMDA receptors in the rat carotid body

“…Characteristically, this enhanced activity and gain significantly outlast the duration of the hypoxic exposure (10). Originally, this gradual increase in chemosensitivity was attributed to acid-base changes occurring in the central nervous system (3,10).…”

“…Characteristically, this enhanced activity and gain significantly outlast the duration of the hypoxic exposure (10). Originally, this gradual increase in chemosensitivity was attributed to acid-base changes occurring in the central nervous system (3,10). Considerable evidence now suggests, however, that short-term acclimatization is mediated primarily through changes in the carotid chemoreceptor rather than through central mechanisms (2).…”