title: Doxapram produces a dose-dependent reduction in the shivering threshold in rabbits.
abstract: Dopamine is a thermoregulatory neurotransmitter that provokes hypothermia when injected in or near the hypothalamus. Doxapram stimulates release of dopamine from carotid bodies, but is known to have central effects that are probably, at least in part, similarly mediated. We thus tested the hypothesis that doxapram produces a substantial, dose-dependent reduction in the shivering threshold in rabbits. Twenty-four rabbits, anesthetized with isoflurane, were randomly assigned to 1) saline (control), 2) 0.25 mg x kg(-1) x h(-1) doxapram, or 3) 0.50 mg x kg(-1) x h(-1) doxapram. These doses are within the recommended range for humans. Body temperature was reduced at a rate of 2 degrees to 3 degrees C/h by perfusing water at 10 degrees C through a U-shaped thermode positioned in the colon. Core temperatures were recorded from the distal esophagus. A blinded observer evaluated shivering. Core temperature at the onset of shivering defined the threshold. Data were analyzed with a one-way analysis of variance; P < 0.05 was considered statistically significant. Hemodynamic and respiratory responses were comparable in the groups. The control rabbits shivered at 36.3 degrees +/- 0.3 degrees C, those given 0.25 mg x kg(-1) x h(-1) doxapram shivered at 34.8 degrees +/- 0.5 degrees C, and those given 0.50 mg x kg(-1) x h(-1) shivered at 33.7 degrees +/- 0.6 degrees C. All the shivering thresholds significantly (P < 0.001) differed from one another. The magnitude of this inhibition, if similar in humans, would be clinically important.
authors.affiliation: Departments of Anesthesia, *University of Yamanashi, Faculty of Medicine, Yamanashi; †Tokyo Women's Medical University, and ‡Tokyo University School of Medicine, Tokyo, Japan; and §Outcomes Research™ Institute and Departments of Anesthesiology, University of Louisville, Louisville, Kentucky.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Okuyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsukawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Ozaki
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Imamura
authors.forename: Teruo
authors.initials: T
authors.lastname: Kumazawa
mesh_terms: D000769:Anesthesia, Inhalation; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004315:Doxapram / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D011817:Rabbits; D015656:Respiratory Mechanics / Q000187:drug effects; D019141:Respiratory System Agents / Q000494:pharmacology*; D012768:Shivering / Q000187:drug effects*
chemical_list: D019141:Respiratory System Agents; D004315:Doxapram