[Effect of flumazenil on hypoglossal and phrenic nerves activities in rabbits].

BACKGROUND: Upper airway obstruction and inadequate ventilation often arise during sedation and anesthesia by benzodiazepines (Bz). Flumazenil antagonizes these effects of active benzodiazepines on the central nervous system. To estimate the influence of flumazenil on the endogenous Bz system related respiratory control, we studied the effect of flumazenil and diazepam on the neural activity and the respiratory response caused by a brief (60 sec) respiratory arrest (RA) manifested in the hypoglossal nerve (HG) and the phrenic nerve (PH) activities in rabbits. METHODS: Experiments were performed on adult rabbits which were vagotomized, paralyzed and artificially ventilated with 50% N2O, 50% oxygen and 0.5% sevoflurane. We evaluated and compared the effects of the sequential administrations of flumazenil and diazepam on the peak amplitude (AMP) as well as the root mean square (RMS) of HG and PH, and respiratory cycle (Tc). RESULTS: Flumazenil by itself increased HG activity more than PH activity with no influence on Tc. But it was not dose-related. Previous administration of flumazenil in total dose of 0.25 mg x kg(-1) could not prevent the anticipated respiratory depression caused by diazepam 2.0 mg x kg(-1). These depressions are greater in HG activity than in PH activity. Additional flumazenil 0.15 mg x kg(-1) following the administration of diazepam promptly reversed these inhibitory effects on HG activity beyond the control level. The same dose of flumazenil, however, did not reverse PH activity sufficiently. RA response was characterized by raised AMPs and augmented RMSs (deltaAMPs, deltaRMSs) with marked prolongation in Tc (deltaTc). Flumazenil and diazepam did not seem to have any influence upon these RA responses. There was a significant change in cardiovascular parameters with the tested dosages of flumazenil and diazepam, but the change was in the normal physiological range. CONCLUSIONS: These results suggest the possibility that the endogenous benzodiazepine system is likely to play an inhibitory role in the regulation of respiration, especially in the maintenance of upper airway patency but the system is unrelated to the chemosensitive-respiratory control.

[Propofol depresses the activity of hypoglossal nerve more than that of phrenic nerve in rabbits].

BACKGROUND: Respiratory depression, such as obstruction of upper airway and inadequate ventilation, often appears during sedation and anesthesia. We studied the effect of propofol on the upper airway patency and the inspiratory drives. METHODS: Experiments were performed on the adult rabbits vagotomized, paralyzed and ventilated with nitrous oxide-oxygen-sevoflurane. We evaluated and compared depressant effect of propofol on the peak amplitude of both hypoglossal nerve (AMP-HG) and phrenic nerve (AMP-PH) activities, inspiratory time (Ti), expiratory time (Te) and respiratory cycle (Tc). RESULTS: Bolus injections of propofol transiently reduced AMP-HG more than AMP-PH (18 and 70% of control, respectively). But AMPs returned to the control levels about 10-15 min after the injection. For 0.5 mg.kg-1.min-1 continuous infusion, propofol soon began to reduce both AMPs. AMP-HG was reduced to about 20% and AMP-PH to 60% of control. Administration of propofol with 1.0 mg.kg-1.min-1 caused more reduction in AMPs with respiratory slowing and AMP-HG disappeared in some animals. CONCLUSION: During the sedation with low dose of propofol, we need to pay attention to potential upper airway obstruction. In addition to the above, high doses of propofol could reduce spontaneous inspiratory drive, and we need to keep both upper airway patency and sufficient ventilation.