Brain stem extracellular fluid pH and respiratory drive during hypoxia in newborn pigs

In response to moderate hypoxia many newborn animals are capable of increasing ventilation only transiently. To examine the hypothesis that changes in brain stem extracellular fluid (ECF) pH explain this transient ventilatory response, we measured brain stem ECF pH and respiratory drive during hypoxia in newborn pigs. The animals were anesthetized with alpha-chloralose-urethan, paralyzed, vagotomized, and mechanically ventilated with a servo-controlled ventilator to regulate end-tidal CO2. Hypoxic ventilation for 6 min was achieved by changing inspired gas from 100% to 10-15% O2. Respiration, measured as integrated phrenic nerve activity, showed a range of responses. In 13 trials increased phrenic activity early in the hypoxic period was sustained or further augmented for the duration of the period. In contrast, in eight other trials phrenic activity increased and then declined. Regardless of the respiratory response, ECF pH (measured with a flat-surface electrode) increased slightly (0.009 +/- 0.002 U) during the first 2.5 min of hypoxia and then declined 0.061 +/- 0.017 U by the 6th min. This acidotic shift in ECF pH is inconsistent with the hypothesis that an alkalotic shift causes the nonsustained respiratory response of newborn pigs.