Sites of Action of Halothane on Respiratory Pattern and Ventilatory Response to CO2 in Cats

Abstract
To assess the major sites of action of halothane on the control of breathing, the ventilatory response to CO2 was studied in 11 cats and partitioned into tidal volume and frequency response. In these cats artificial perfusion of the ponto-medullary region was applied. This technique allows delivery to the brainstem of blood-gas tensions and anesthetic concentrations at predetermined levels independent of those in the systemic circulation; thus the central and peripheral effects of halothane and CO2 can be determined separately. In cats exposed both centrally and peripherally to halothane (1.0-1.6%) tachypnea was observed which disappeared when the blood perfusing the brainstem was purged of halothane. Apparently, the tachypnea is exclusively due to an action of halothane on structures in the brainstem. In these cats the extrapolated PaCO2 [arterial CO2 tension] at zero ventilation was significantly lower during general halothane anesthesia than during light chloralose-urethane anesthesia (P < 0.05). In cats lightly anesthetized with chloralose-urethane, halothane (0.5-1.5%) was either administered centrally or peripherally. In these experiments the overall ventilatory CO2 sensitivity of both the peripheral and central chemorereflex pathways decreased significantly (P < 0.01). The ratio between these 2 sensitivities remained the same (P > 0.5). The extrapolated PaCO2 at zero ventilation was not affected by halothane provided its concentration was below 1% (P > 0.7). Evidently, the depressant effect of halothane on ventilation originates centrally as well as peripherally. From the findings that the ratio of the CO2 sensitivities and the extrapolated PaCO2 at zero ventilation remained constant, it seems that halothane may act on the processing part of the neural respiratory derive (integrating centers) rather than on the neural activity of the peripheral and central chemoreceptors per se. The peripheral effect is mainly on the neuromechanical link between integrating centers and respiratory movements.