title: Effects of the alpha2-adrenoceptor agonist dexmedetomidine on bronchoconstriction in dogs.
abstract: BACKGROUND
  Tracheal intubation can elicit reflex bronchoconstriction in patients with asthma or chronic obstructive pulmonary disease, complicating mechanical ventilation and weaning from mechanical support. In vitro studies of human and animal bronchial tissue indicate that alpha2-adrenoceptor stimulation can lead to smooth muscle relaxation and prevention of bronchoconstriction. Dexmedetomidine is a selective alpha2-adrenoceptor agonist approved for sedation in the intensive care unit. Whether dexmedetomidine can affect reflex bronchoconstriction is unknown.
  
  
  METHODS
  After the approval of the institutional animal care and use committee, five mongrel dogs were anesthetized with thiopental, endotracheally intubated, and ventilated, and their airways were challenged with histamine. High-resolution computed tomography was used to measure airway luminal areas at baseline and after nebulized histamine. After recovery to baseline, on separate days, dexmedetomidine (0.5 microg/kg) was administered either intravenously or as an aerosol, and the histamine challenge was repeated.
  
  
  RESULTS
  At baseline, histamine constricted the airways to 66 +/- 27% (mean +/- SD) (P < 0.0001) and 59 +/- 30% (P < 0.0001) of maximum on the days dexmedetomidine was administered by intravenous and inhalational means, respectively. After recovery, intravenous administration of dexmedetomidine blocked the histamine-induced bronchoconstriction (87 +/- 30.4% of maximum, compared with histamine alone (P < 0.0001), whereas dexmedetomidine administered by inhalation showed no protective effect (45 +/- 30% of maximum; P < 0.0001 compared with histamine alone).
  
  
  CONCLUSIONS
  alpha2-Adrenoceptor stimulation with intravenous dexmedetomidine completely blocked histamine-induced bronchoconstriction in dogs. Therefore, dexmedetomidine might be beneficial to decrease airway reactivity in patients with chronic obstructive pulmonary disease or asthma, particularly during weaning from mechanical ventilation, when neurally mediated airway reflexes may be elicited.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany. harald.groeben@uni-essen.de
authors.forename: Harald
authors.initials: H
authors.lastname: Groeben
authors.forename: Wayne
authors.initials: W
authors.lastname: Mitzner
authors.forename: Robert H
authors.initials: RH
authors.lastname: Brown
mesh_terms: D000280:Administration, Inhalation; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000336:Aerosols; D000818:Animals; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D006633:Histamine Antagonists / Q000494:pharmacology*; D007275:Injections, Intravenous; D014057:Tomography, X-Ray Computed
chemical_list: D000316:Adrenergic alpha-Agonists; D000336:Aerosols; D006633:Histamine Antagonists; D020927:Dexmedetomidine