title: Dose-dependent increases in the renal sympathetic nerve activity during rapid increase in isoflurane concentration in intact, lower airway-deafferented, and baroreceptor-deafferented rabbits.
abstract: BACKGROUND
  The inhalation of high concentrations of isoflurane has been reported to increase the heart rate and the concentration of serum catecholamines. Although the precise mechanisms for the sympathetic activation of isoflurane have yet to be clearly elucidated, they are considered to possibly originate from the stimulation of airway sensory afferents, the baroreceptor reflex, or the direct stimulation of the central nervous system. To determine how these three mechanisms contribute to sympathetic augmentation, the effects of lower airway deafferentation and baroreceptor deafferentation on the isoflurane-induced changes in the renal sympathetic nerve activity (RSNA) in tracheally intubated rabbits were examined.
  
  
  METHODS
  Twenty rabbits were given basal anesthesia. After tracheotomy and during mechanical ventilation, the changes in the heart rate, mean arterial pressure, and RSNA in response to random exposures to 1%, 2%, 3%, and 4% isoflurane were examined. The animals were assigned to one of three groups; 1, the intact group (n = 6); 2, the baroreceptor-deafferented group (n = 9), in which the sinoaortic plus vagal nerves were cut; and 3, the lower airway-deafferented group (n = 5), which underwent a bilateral vagotomy. The exposure to isoflurane was for 10 min in group 1 and 5 min in groups 2 and 3. At least 1 h was allowed for the recovery interval between exposures to isoflurane.
  
  
  RESULTS
  The inhalation of isoflurane caused dose-dependent increases in RSNA in all three groups. RSNA during high concentrations of isoflurane began to increase at 1 min, reaching the maximum at 4 or 5 min in group 1 (2.8- and 3.8-fold at 3% and 4% isoflurane, respectively) and group 3 (2.8- and 4.5-fold at 3% and 4% isoflurane, respectively), but it reached the peak at 2 or 3 min in group 2 (1.7- and 2.4-fold at 3% and 4% isoflurane, respectively) after the initiation of inhalation, in association with early slight increases followed by decreases of mean arterial pressure in groups 1 and 2 but only gradual decreases of mean arterial pressure in group 3. The increases in RSNA in group 3 were similar to group 1, however, those in group 2 were significantly attenuated compared with group 1.
  
  
  CONCLUSIONS
  The inhalation of isoflurane caused an increase of RSNA in intact, baroreceptor-deafferented, and lower airway-deafferented rabbits. The extent of the increases in RSNA was greater in intact and lower airway-deafferented rabbits than in baroreceptor-deafferented rabbits. Therefore, it is suggested that isoflurane may increase the efferent sympathetic nerve activity via the direct stimulation of the central nervous system and via the arterial baroreceptor reflex reflecting the reduction in arterial blood pressure. The stimulation of the vagally innervated airway may not contribute to the increase in the sympathetic nerve activity by isoflurane.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Okamoto
authors.forename: S
authors.initials: S
authors.lastname: Hoka
authors.forename: T
authors.initials: T
authors.lastname: Kawasaki
authors.forename: T
authors.initials: T
authors.lastname: Okuyama
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000344:Afferent Pathways / Q000502:physiology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology*; D007668:Kidney / Q000294:innervation*; D011311:Pressoreceptors / Q000502:physiology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane