Modification of phrenic nerve output to hypoxia after two hours of hypercapnia and increased cerebrospinal fluid [HCO3-].

Decreased ventilatory response to hypoxia has been reported in patients with CO2 retention. The CO2 retention increases cerebrospinal fluid (CSF) [HCO3-], which could modify the ventilatory response to hypoxia. In order to evaluate the effect of increased CSF [HCO3-] as a consequence of hypercapnia on the response to hypoxia, phrenic nerve output during 5 min of progressive hypoxia was measured in anesthetized vagotomized and mechanically ventilated dogs when their acid-base was normal and when CSF [HCO3-] had increased. Peak phrenic nerve activity (PPNA), inspiratory time (TI), and expiratory time (TE) were recorded in 2 groups of dogs. Two hypoxic tests were conducted 2.5 h apart in each group. One group had normal acid-base status and the second group after the first hypoxic challenge breathed 10% CO2 for 2 h, and then ventilation was adjusted to bring CSF pH back to normal. The CSF [HCO3-] then had increased by 5.2 mEq/L and CSF PCO2 was 14.6 mmHg higher. With CSF [HCO3-] elevation, PPNA activity in response to hypoxia was significantly depressed, compared with that in animals with normal acid-base balance, TI was increased indicating slowing of nerve discharge, and TE was minimally increased indicating lessening of frequency of neural bursts. We conclude that the metabolic component of acid-base balance in the central nervous system can influence the neural output of the respiratory centers in response to hypoxia as manifested by phrenic nerve output, and increased CSF [HCO3-] seen with hypercapnia is associated with depressed hypoxic response.