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Cardiovascular and sedation reversal effects of intramuscular administration of atipamezole in dogs treated with medetomidine hydrochloride with or without the peripheral α2-adrenoceptor antagonist vatinoxan hydrochloride

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  • 1 1Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00100 Helsinki, Finland.
  • | 2 2Clinical Unit of Anaesthesiology and Perioperative Intensive Care Medicine, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
  • | 3 3Pharmacology Department, Faculty of Veterinary Medicine, Beni-Suef University, 62511 Beni-Suef, Egypt.
  • | 4 4Institute of Biomedicine, University of Turku and Unit of Clinical Pharmacology, Turku University Hospital, 20520 Turku, Finland.
  • | 5 5Department of Statistics, 4Pharma Ltd, Tykistökatu 4, 20520 Turku, Finland.
  • | 6 6Admescope Ltd, Typpitie 1, 90620 Oulu, Finland.

Abstract

OBJECTIVE

To investigate the cardiovascular and sedation reversal effects of IM administration of atipamezole (AA) in dogs treated with medetomidine hydrochloride (MED) or MED and vatinoxan (MK-467).

ANIMALS

8 purpose-bred, 2-year-old Beagles.

PROCEDURES

A randomized, blinded, crossover study was performed in which each dog received 2 IM treatments at a ≥ 2-week interval as follows: injection of MED (20 μg/kg) or MED mixed with 400 μg of vatinoxan/kg (MEDVAT) 30 minutes before AA (100 μg/kg). Sedation score, heart rate, mean arterial and central venous blood pressures, and cardiac output were recorded before and at various time points (up to 90 minutes) after AA. Cardiac and systemic vascular resistance indices were calculated. Venous blood samples were collected at intervals until 210 minutes after AA for drug concentration analysis.

RESULTS

Heart rate following MED administration was lower, compared with findings after MEDVAT administration, prior to and at ≥ 10 minutes after AA. Mean arterial blood pressure was lower with MEDVAT than with MED at 5 minutes after AA, when its nadir was detected. Overall, cardiac index was higher and systemic vascular resistance index lower, indicating better cardiovascular function, in MEDVAT-atipamezole–treated dogs. Plasma dexmedetomidine concentrations were lower and recoveries from sedation were faster and more complete after MEDVAT treatment with AA than after MED treatment with AA.

CONCLUSIONS AND CLINICAL RELEVANCE

Atipamezole failed to restore heart rate and cardiac index in medetomidine-sedated dogs, and relapses into sedation were observed. Coadministration of vatinoxan with MED helped to maintain hemodynamic function and hastened the recovery from sedation after AA in dogs.

Contributor Notes

Address correspondence to Dr. Turunen (hetamarju.turunen@helsinki.fi).