Abstract
Background: Sedation with Benzodiazepines (Bz) often causes upper airway obstruction. It comes from the fact that Bz inhibits the hypoglossal nerve activity (HGA) via the Bz-GABAA receptor complex systems. This study aimed to investigate how the pre-injection of bicuculline (BIC: a competitive GABAA antagonist) and/or picrotoxin (PIC: a non-competitive GABAA antagonist) modulate the effect of flumazenil (FLU: a competitive Bz antagonist) on the diazepam (Dz)-inhibited hypoglossal activity (Dz-I).
Methods: Studies were carried out in adult rabbits (n=24) which were vagotomized, paralyzed and ventilated with 50% N2O, 50% O2 and 0.5% sevoflurane. This experiment is composed of the following three steps. The first step was Dz-I. The second step was injections of antagonists. Based on the tested antagonists, we divided the rabbits into five groups: Group one, no antagonists for sham treatment; group two, FLU; group three, PIC; group four, BIC; and group five, BIC and PIC. The final step was the injection of FLU for all groups.
We measured the root mean square (RMS) in integrated hypoglossal neurogram for data analysis.
Results: Dz-I is characterized by a rough 40-50% decrease in RMS. FLU antagonized Dz-I promptly with a short duration of antagonism and induced neither cumulation, potentiation nor tachyphylaxis in the subsequent FLU induced responses (see Fig.5-1&2). PIC gradually reversed Dz-I with a longer duration of antagonism than FLU alone, and allowed the next FLU to cause a marked excitation in HGA going up to approximately 50% over the control (refer to Fig.5-3). After BIC injection (see Fig.5-4), there were no significant changes in Dz-I like the results show in the sham treatment (see Fig.5-1), except for a transient trivial excitation that appeared following FLU injection. Co-injection of PIC with BIC facilitated the process of Dz-I recovery compared with PIC alone and inhibited the next FLU induced excitation in HGA substantially (see Fig.5-5).
Conclusion: These results suggest that the FLU-induced HGA excitation in Dz-I, which is only triggered by pre-administrated PIC, seems to be mainly controlled via PIC-sensitive Bz-GABAA receptor complex system and the other BIC-modulated GABAA constituents may secondarily affect the excitation.
