Disruption of the Rhythmic Activity of the Medullary Inspiratory Neurons and Phrenic Nerve by Fentanyl and Reversal with Nalbuphine

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Abstract
The effects of intravenous administration of fentanyl (50 and 100 .mu.g/kg) on the discharge activity of the medullary inspiratory neurons and of the phrenic nerve were studied following vagotomy in nine decerebrate, paralyzed mechanically ventilated cats. In six cats, the inspiratory neurons explored were in the dorsal respiratory group (DRG) associated with the nucleus of the tractus solitarius (NTS), while in the remaining three, they were in the ventral respiratory group (VRG). In the former group, the rhythmic discharge of the inspiratory neurons was disrupted by fentanyl and replaced by a continuous discharge superimposed with irregularly occurring bursts. These charges were also reflected by the phrenic nerve discharge. Inspiratory neuronal activity increased significantly (P < 0.05) at 1 and 5 min after completion of fentanyl injection. Disruption of the rhythmic activity of the inspiratory neurons and its replacement by a continuous and irregular discharge may lead to sustained contraction of inspiratory muscles and cessation of respiration. In the VRG, the activity of the inspiratory neurons was totally abolished by fentanyl. Thus, it appears that different groups of medullary inspiratory neurons have differential sensitivity to fentanyl. Nalbuphine, an opiate agonist-antagonist, restored the normal pattern and magnitude of the activity of the inspiratory neurons.