title: Detomidine and the combination of detomidine and MK-467, a peripheral alpha-2 adrenoceptor antagonist, as premedication in horses anaesthetized with isoflurane.
abstract: OBJECTIVE
  To investigate MK-467 as part of premedication in horses anaesthetized with isoflurane.
  
  
  METHODS
  Experimental, crossover study with a 14 day wash-out period.
  
  
  METHODS
  Seven healthy horses.
  
  
  METHODS
  The horses received either detomidine (20 μg kg(-1) IV) and butorphanol (20 μg kg(-1) IV) alone (DET) or with MK-467 (200 μg kg(-1) IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg(-1) ) and midazolam (0.06 mg kg(-1) ) IV and maintained with isoflurane. Heart rate (HR), mean arterial pressure (MAP), end-tidal isoflurane concentration, end-tidal carbon dioxide tension, central venous pressure, fraction of inspired oxygen (FiO2 ) and cardiac output were recorded. Blood samples were taken for blood gas analysis and to determine plasma drug concentrations. The cardiac index (CI), systemic vascular resistance (SVR), ratio of arterial oxygen tension to inspired oxygen (Pa O2 /FiO2 ) and tissue oxygen delivery (DO2 ) were calculated. Repeated measures anova was applied for HR, CI, MAP, SVR, lactate and blood gas variables. The Student's t-test was used for pairwise comparisons of drug concentrations, induction times and the amount of dobutamine administered. Significance was set at p < 0.05.
  
  
  RESULTS
  The induction time was shorter, reduction in MAP was detected, more dobutamine was given and HR and CI were higher after DET+MK, while SVR was higher with DET. Arterial oxygen tension and Pa O2 /FiO2 (40 minutes after induction), DO2 and venous partial pressure of oxygen (40 and 60 minutes after induction) were higher with DET+MK. Plasma detomidine concentrations were reduced in the group receiving MK-467. After DET+MK, the area under the plasma concentration time curve of butorphanol was smaller.
  
  
  CONCLUSIONS
  MK-467 enhances cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia. This finding could improve patient safety in the perioperative period. The dosage of MK-467 needs to be investigated to minimise the effect of MK-467 on MAP.
authors.affiliation: Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Soile Ae
authors.initials: SA
authors.lastname: Pakkanen
authors.affiliation: Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Marja R
authors.initials: MR
authors.lastname: Raekallio
authors.affiliation: Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Mykkänen
authors.affiliation: Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Kati M
authors.initials: KM
authors.lastname: Salla
authors.affiliation: Animal Health Trust, Newmarket, Suffolk, UK.
authors.forename: Annemarie
authors.initials: A
authors.lastname: de Vries
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.|Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.
authors.forename: Lauri
authors.initials: L
authors.lastname: Vuorilehto
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.|Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Scheinin
authors.affiliation: Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Outi M
authors.initials: OM
authors.lastname: Vainio
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage*; D000769:Anesthesia, Inhalation / Q000662:veterinary; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D000818:Animals; D001182:Arthroscopy / Q000662:veterinary; D018592:Cross-Over Studies; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006736:Horses / Q000502:physiology* / Q000601:surgery; D007093:Imidazoles / Q000008:administration & dosage*; D007530:Isoflurane / Q000008:administration & dosage; D008297:Male; D011292:Premedication / Q000662:veterinary*; D011807:Quinolizines / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D018686:Anesthetics, Intravenous; D007093:Imidazoles; D011807:Quinolizines; C055732:vatinoxan; C041255:detomidine; D007530:Isoflurane
keywords: MK-467; arterial blood pressure; detomidine; horses; systemic vascular resistance