title: Clonidine induces upper airway closure in awake goats.
abstract: We examined the effects of the alpha(2)-adrenoceptor (alpha(2)-AR) agonist clonidine on pressure-flow relationships in the upper airway. Inspired and expired airflows, subglottic tracheal pressure (PTR), mask pressure and middle pharyngeal constrictor (MPC) and diaphragm electromyogram (EMG) activities were recorded in awake standing goats. Clonidine-induced central apneas were always associated with continuous tonic activation of the MPC. Subglottic PTR during expiration increased progressively in a dose-dependent manner after clonidine administration. In all cases, positive subglottic PTR was maintained throughout the duration of clonidine-induced apneas and was sufficient to retard or prevent expiratory flow during early and mid-expiration indicating complete airway closure. The effects of clonidine were reversed by selective alpha(2)-AR blockade with SKF-86466. Central apneas after spontaneous augmented breaths (sighs) were associated with continuous tonic activation of the MPC throughout the duration of the prolonged TE intervals. However, subglottic PTR during expiration was not significantly different from control breaths and there was no evidence of increased expiratory airway resistance or delayed expiratory flow. We conclude that continuous tonic activation of pharyngeal adductor muscles appears to be a constant feature of central apnea in the awake goat independent of the initiating cause of the apnea. However, our data suggest that MPC activation alone may not be sufficient to cause complete closure of the upper airway during central apnea.
authors.affiliation: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Dr. West, Madison, WI 53706-1102, USA. ken.ohalloran@ucd.ie
authors.forename: K D
authors.initials: KD
authors.lastname: O'Halloran
authors.forename: J K
authors.initials: JK
authors.lastname: Herman
authors.forename: G E
authors.initials: GE
authors.lastname: Bisgard
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001049:Apnea / Q000139:chemically induced; D001552:Benzazepines / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D003243:Consciousness; D003964:Diaphragm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004576:Electromyography / Q000187:drug effects; D005260:Female; D006041:Goats / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects*; D010609:Pharyngeal Muscles / Q000187:drug effects / Q000502:physiology; D011312:Pressure; D012123:Pulmonary Ventilation / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001552:Benzazepines; D003000:Clonidine; C039139:benalfocin