title: Acoustic rhinometry in the dog: a novel large animal model for studies of nasal congestion.
abstract: The aim of this project was to develop and pharmacologically characterize an experimental dog model of nasal congestion in which nasal patency is measured using acoustic rhinometry. Solubilized compound 48/80 (0.3-3.0%) was administered intranasally to thiopental anesthetized beagle dogs to elicit nasal congestion via localized mast cell degranulation. Compound 48/80-induced effects on parameters of nasal patency were studied in vehicle-treated animals, as well as in the same animals pretreated 2 hours earlier with oral d-pseudoephedrine or chlorpheniramine. Local mast cell degranulation caused a close-related decrease in nasal cavity volume and minimal cross-sectional area (Amin) together with a highly variable increase in nasal secretions. Maximal responses were seen at 90-120 minutes after 48/80 administration. Oral administration of the adrenergic agonist, d-pseudoephedrine (3.0 mg/kg), significantly antagonized all of the nasal effects of compound 48/80 (3.0%). In contrast, oral administration of the histamine H1 receptor antagonist chlorpheniramine (10 mg/kg) appeared to reduce the increased nasal secretions but was without effect on the compound 48/ 80-induced nasal congestion (i.e., volume and Amin). These results show the effectiveness of using acoustic rhinometry in this anesthetized dog model. The observations that compound 48/80-induced nasal congestion was prevented by d-pseudoephedrine pretreatment, but not by chlorpheniramine, suggest that this noninvasive model system may provide an effective tool with which to study the actions of decongestant drugs in preclinical investigations.
authors.affiliation: Department of Cell Biology, University of Oklahoma, College of Medicine, Oklahoma City 73190, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Koss
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Yu
authors.forename: John A
authors.initials: JA
authors.lastname: Hey
authors.forename: Robbie L
authors.initials: RL
authors.lastname: McLeod
mesh_terms: D000162:Acoustics; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D002744:Chlorpheniramine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D004347:Drug Interactions; D004809:Ephedrine / Q000494:pharmacology*; D008297:Male; D015508:Nasal Obstruction / Q000175:diagnosis* / Q000188:drug therapy*; D010036:Otolaryngology / Q000379:methods*; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D002744:Chlorpheniramine; D004809:Ephedrine