Central respiratory depression induced by acetylcholinesterase inhibition: involvement of anaesthesia

We have studied the effects of anaesthesia on the changes in central respiratory activity following the inhibition of acetylcholinesterase in chronically implanted cats. The organophosphate paraoxon was administered to the brainstem respiratory centres by intracerebroventricular (i.c.v.) injection (3 mg) into the IVth ventricle, thus avoiding peripheral effects such as paralysis of respiratory muscles. Paraoxon had opposite effects on respiratory activity depending on whether the cats were anaesthetized or not: it induced respiratory depression and sometimes respiratory arrest during pentobarbital (30 mg/kg i.v.) or halothane anaesthesia, but in the same animals in the waking state, the same dose of paraoxon always stimulated respiration. These results show a strong interaction between anaesthetics and the effects of acetylcholine (ACh) accumulation on central respiratory activity. This study extends previous results showing an interaction between ACh and pentobarbital on single respiratory neurons and stresses the importance of a 'wakefulness stimulus' for sustaining respiratory activity after organophosphate poisoning.