Dose-dependent effects of isoflurane on the CO2 responses of expiratory medullary neurons and the phrenic nerve activities in dogs.

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Expiratory bulbospinal neurons (EBS) neurons in the region of the nucleus retroambigualis provide a major source of drive for thoracic and abdominal expiratory motoneurons. These studies examined the dose-dependent effects of isoflurane anesthesia from 0.5-2.5 minimum alveolar concentration (MAC) on the CO2 responses of extracellularly recorded single EBS neurons and phrenic neural activities in unpremedicated, anesthetized, paralyzed, vagotomized dogs. Hyperventilation with O2 and the addition of CO2-O2 mixtures were used to produce three steady-state levels of central CO2 drive: low, medium, and high with corresponding mean PaCO2 values of 29, 45, and 67 mmHg. Plots of peak expiratory neuron discharge frequency (Fn) versus steady-state levels of isoflurane dose showed a progressive decrease in Fn for both high and medium drive levels, whereas for low drive most neurons fired tonically at all MAC levels with little change in Fn. Peak phrenic activity showed a similar but more pronounced decline with increased MAC for all levels of CO2 drive. Increasing isoflurane dose caused a downward, predominantly parallel shift of the CO2 response curves for both expiratory neuronal and phrenic neural activities. Phrenic activity ceased at 2-2.5 MAC isoflurane for all CO2 drive levels, whereas EBS neurons continued to fire tonically at the same depth at 30-50% of Fn at 1 MAC for the high level. These studies suggest that phrenic (inspiratory) activity is more sensitive than EBS neurons to isoflurane and that increases in CO2 drive can only partially offset the depressant effect of isoflurane on central respiratory activities.