Evidence for cerebral extracellular fluid [H +] as a stimulus during acclimatization to hypoxia

Abstract

Ventilation and CSF and plasma acid-base composition were measured in 5 pentobarbital anesthetized dogs at 30 min intervals during 3 hr of hypoxia. The hypoxia initiated a large increase in ventilation measured after the first 30 min and a smaller secondary increase which was complete by the 2nd hr. After 3 hr, CSF [H4 +]was not significantly different from its control value. However, the secondary increase in ventilation after the initial response could not be accounted for by changes in CSF [H + since the changes in ventilation preceded CSF [H + by 30 min. Between 30 and 60 min there was a statistically significant increase in ventilation (P <0.005) and a statistically significant decrease in CSF [H +](P<0. 03). The presence of a CSF to blood [HCO − 3]gradient suggested a role for cerebral ECF acidity in the ventilatory response. We calculated ECF [H + bathing a hypothetical ventilatory chemosensitive area assumed to be located 3/4 of the way along this [HCO − 3]gradient, closer to blood. In contrast to CSF [H +], ECF [H +]increased between 30 and 60 min and could account for the secondary increase in ventilation after the initial response. These data suggest that a part of the early phase of ventilatory acclimatization to hypoxia is initiated by these changes in brain ECF [H +].