Pentobarbital sedation increases genioglossus respiratory activity in sleeping rats

Objective: To determine whether certain sedatives may, by increasing arousal threshold, allow pharyngeal dilator muscle activity to increase more in response to chemical stimuli before arousal occurs. Design, Participants and Interventions: Thirteen chronically instrumented rats were studied during sleep following injections of placebo or sedating doses of pentobarbital (10mg/kg). Intermittently, inspired CO2 was increased gradually until arousal occurred. Measurements and Results: Maximum genioglossus activity reached before arousal was higher with pentobarbital than placebo (34.5 +/- 24.3 vs 3.7 +/- 2.9mV; P<0.001) for 2 reasons. First, genioglossus activity was greater during undisturbed sleep before CO2 was applied (23.3 +/- 15.3 vs 2.5 +/- 1.5 mV, P<0.001). When sleep periods were long, a ramp-like increase in genioglossus activity (GG-Ramp) began and progressed until arousal. GG-Ramps developed with both placebo and pentobarbital but reached higher levels with pentobarbital due to longer sleep periods and faster increase in genioglossus activity during the ramp. GG-Ramps began when diaphragm activity was lowest and progressed despite unchanged diaphragm activity. Second, as hypothesized, the increase in genioglossus activity with CO2 before arousal was greater than with placebo (11.2 +/- 2.5 vs 1.2 +/- 2.5mV; P<0.05) due to increased arousal threshold. In 27 of 126 CO2 challenges delivered while GG-Ramps were in progress, genioglossus activity paradoxically decreased despite increased diaphragmatic activity. These negative responses occurred randomly in 7 of 13 rats. Conclusions: In rats: 1) Sedatives may allow genioglossus activity to reach higher levels during sleep. 2) A time-dependent increase in genioglossus activity occurs during undisturbed sleep that is unrelated to chemical drive. 3) Transient hypercapnia may elicit inhibition of genioglossus activity under currently unidentified circumstances.