DOSE-DEPENDENT EFFECTS OF HALOTHANE ON THE PHRENIC-NERVE RESPONSES TOACUTE-HYPOXIA IN VAGOTOMIZED DOGS

Background: Previous studies in dogs and humans suggest that the carot id body chemoreceptor response to hypoxia is selectively impaired by h alothane. The present studies in an open-loop canine preparation were performed to better delineate the effects of anesthetic concentrations of halothane an the carotid body chemoreceptor-mediated phrenic nerve response to an acute hypoxic stimulus. Methods: Three protocols were performed to study the effects of halothane anesthesia on the phrenic nerve response to 1 min of isocapnic hypoxia (partial pressure of oxyg en [Pa-O2] at peak hypoxia, 35-38 mmHg) in unpremedicated, anesthetize d, paralyzed, vagotomized dogs during constant mechanical ventilation. In protocol 1, the dose-dependent effects of halothane from 0.5-2.0 m inimum alveolar concentration (MAC) on the hypoxic response during mod erate hypercapnia (partial pressure of carbon dioxide [Pa-CO2], 60-65 mmHg) were studied in 10 animals. In protocol 2, the hypoxic responses at 1 MAC halothane near normocapnia (Pa-CO2, 40-45 mmHg) and during m oderate hypercapnia were compared in an additional four animals. In pr otocol 3, the hypoxic response of 4 of 10 dogs from protocol 1 was als o studied under sodium thiopental (STP) anesthesia after they complete d protocol 1. Results: Protocol 1: Peak phrenic nerve activity (PPA) i ncreased significantly during the hypoxic runs compared with the isoca pnic hyperoxic controls at all halothane doses. The phrenic nerve resp onse to the hypoxic stimulus was present even at the 3 MAC dose. Proto col 2: The net hypoxic responses for the two carbon dioxide background levels at 1 MAC were not significantly different. Protocol 3: The net hypoxic response of PPA. for the STP anesthetic was not significantly different from the 1 MAC halothane dose, Bilateral carotid sinus dene rvation abolished the PPA response to hypoxia. Conclusions: The phreni c nerve response to an acute, moderately severe isocapnic hypoxic stim ulus is dose-dependently depressed but not abolished by surgical doses of halothane, This analysis does not suggest a selective depression o f the carotid body chemoreceptor response by halothane. The observed h ypoxic phrenic response was mediated hy the carotid body chemoreceptor s in vagotomized dogs because bilateral carotid sinus denervation abol ished all increases in PPA.