title: The effect of detomidine and its antagonism with tolazoline on stress-related hormones, metabolites, physiologic responses, and behavior in awake ponies.
abstract: Six ponies were used to investigate the effect of tolazoline antagonism of detomidine on physiological responses, behavior, epinephrine, norepinephrine, cortisol, glucose, and free fatty acids in awake ponies. Each pony had a catheter inserted into a jugular vein 1 hour before beginning the study. Awake ponies were administered detomidine (0.04 mg/kg intravenously [i.v.]) followed 20 minutes later by either tolazoline (4.0 mg/kg i.v.) or saline. Blood samples were drawn from the catheter 5 minutes before detomidine administration (baseline), 5 minutes after detomidine administration, 20 minutes before detomidine administration which was immediately before the administration of tolazoline or saline (time [T] = 0), and at 5, 30, and 60 minutes after injections of tolazoline or saline (T = 5, 30, and 60 minutes, respectively). Compared with heart rate at T = 0, tolazoline antagonism increased heart rate 45% at 5 minutes. There was no difference in heart rate between treatments at 30 minutes. Blood pressure remained stable after tolazoline, while it decreased over time after saline. Compared with concentrations at T = 0, tolazoline antagonism of detomidine in awake ponies resulted in a 55% increase in cortisol at 30 minutes and a 52% increase in glucose at 5 minutes. The change in free fatty acids was different for tolazoline and saline over time. Free fatty acids decreased after detomidine administration. Free fatty acids did not change after saline administration. After tolazoline administration, free fatty acids increased transiently. Tolazoline tended to decrease sedation and analgesia at 15 and 60 minutes postantagonism. Antagonism of detomidine-induced physiological and behavioral effects with tolazoline in awake ponies that were not experiencing pain appears to precipitate a stress response as measured by cortisol, glucose, and free fatty acids. If antagonism of an alpha-agonist is contemplated, the potential effect on hormones and metabolites should be considered.
authors.affiliation: Department of Small Animal Medicine and Surgery, Texas A&M University, College Station, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Carroll
authors.forename: N S
authors.initials: NS
authors.lastname: Matthews
authors.forename: S M
authors.initials: SM
authors.lastname: Hartsfield
authors.forename: M R
authors.initials: MR
authors.lastname: Slater
authors.forename: T H
authors.initials: TH
authors.lastname: Champney
authors.forename: S W
authors.initials: SW
authors.lastname: Erickson
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003243:Consciousness / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006734:Horse Diseases / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D006736:Horses / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D006854:Hydrocortisone / Q000097:blood; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary; D013997:Time Factors; D014043:Tolazoline / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; C041255:detomidine; D014043:Tolazoline; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine