Effects of volatile anesthetics on respiratory activity and chemosensitivity in the isolated brainstem-spinal cord of the newborn rat

Abstract

To elucidate the various actions of volatile anesthetics on respiratory activity and chemosensitivity, we have studied the activities of the respiration-related structures in the medulla of the in vitro brainstem-spinal cord preparation of the newborn rat. Halothane decreased respiratory burst frequency (fR), inspiratory duration (Ti), integrated ventral C4 root activity (integral of C4) and respiratory minute activity (RMA) in a concentration-dependent fashion. Bicuculline counteracted the depressive effect of halothane on fR, integral of C4, and RMA. Inspiratory neuronal activity recorded at the rostral ventrolateral medulla (RVL) corresponded to these changes. Activities of Pre-Inspiratory (Pre-I) neurons and expiratory neurons in the RVL were also inhibited by halothane. The C4 activity did not always correspond to Pre-I neurons' discharge. In this comparative study of three volatile anesthetics, the inhibitory effect on fR appeared to be greater with enflurane than with halothane or isoflurane. The reversal effects of bicuculline on decreases in fR, integral of C4, and RMA also seemed to be greater with enflurane than with halothane or isoflurane. Hypercapnia (pH 7.0) induced a significant increase in fR and RMA, and a significant decrease in Ti. Although halothane inhibited overall activities, chemo-responsiveness to hypercapnia changed similarly even during halothane application. Hypocapnia (pH 7.8) significantly decreased fR, and increased integral of C4 and Ti. Hypocapnia during halothane application also induced a significant decrease in fR and RMA. These results suggest that the modification of GABAA receptor-mediated neurotransmission is in part responsible for the respiratory depression by volatile anesthetics, affecting especially fR, integral of C4, and RMA. Low respiratory rate by enflurane is associated with GABAergic modification. Prolongation of Ti by enflurane, seen clinically, does not seem to be either central or GABAergic. These findings demonstrate the responsiveness to CO2 and the respiratory compensation mechanism via respiratory frequency in the isolated preparation. It is, furthermore, indicated that halothane preserves the central chemosensitivity while its concentration is high enough to reduce the respiratory activities.