Cardiovascular effects of intravenous vatinoxan (MK-467) in medetomidine-tiletamine-zolazepam anaesthetised red deer (Cervus elaphus)

Vet Anaesth Analg. 2020 Jul;47(4):518-527. doi: 10.1016/j.vaa.2019.10.011. Epub 2020 Mar 29.

Abstract

Objective: To determine the effect of intravenous vatinoxan administration on bradycardia, hypertension and level of anaesthesia induced by medetomidine-tiletamine-zolazepam in red deer (Cervus elaphus).

Study design and animals: A total of 10 healthy red deer were included in a randomised, controlled, experimental, crossover study.

Methods: Deer were administered a combination of 0.1 mg kg-1 medetomidine hydrochloride and 2.5 mg kg-1 tiletamine-zolazepam intramuscularly, followed by 0.1 mg kg-1 vatinoxan hydrochloride or equivalent volume of saline intravenously (IV) 35 minutes after anaesthetic induction. Heart rate (HR), mean arterial blood pressure (MAP), respiration rate (fR), end-tidal CO2 (Pe'CO2), arterial oxygen saturation (SpO2), rectal temperature (RT) and level of anaesthesia were assessed before saline/vatinoxan administration (baseline) and at intervals for 25 minutes thereafter. Differences within treatments (change from baseline) and between treatments were analysed with linear mixed effect models (p < 0.05).

Results: Maximal (81 ± 10 beats minute-1) HR occurred 90 seconds after vatinoxan injection and remained significantly above baseline (42 ± 4 beats minute-1) for 15 minutes. MAP significantly decreased from baseline (122 ± 10 mmHg) to a minimum MAP of 83 ± 6 mmHg 60 seconds after vatinoxan and remained below baseline until end of anaesthesia. HR remained unchanged from baseline (43 ± 5 beats minute-1) with the saline treatment, whereas MAP decreased significantly (112 ± 16 mmHg) from baseline after 20 minutes. Pe'CO2, fR and SpO2 showed no significant differences between treatments, whereas RT decreased significantly 25 minutes after vatinoxan. Level of anaesthesia was not significantly influenced by vatinoxan.

Conclusions and clinical relevance: Vatinoxan reversed hypertension and bradycardia induced by medetomidine without causing hypotension or affecting the level of anaesthesia in red deer. However, the effect on HR subsided 15 minutes after vatinoxan IV administration. Vatinoxan has the potential to reduce anaesthetic side effects in non-domestic ruminants immobilised with medetomidine-tiletamine-zolazepam.

Keywords: bradycardia; hypertension; medetomidine; red deer; vatinoxan.

Publication types

  • Randomized Controlled Trial, Veterinary

MeSH terms

  • Anesthetics, Combined / adverse effects
  • Anesthetics, Intravenous
  • Animals
  • Bradycardia / chemically induced
  • Bradycardia / prevention & control
  • Bradycardia / veterinary
  • Cardiovascular System / drug effects*
  • Cross-Over Studies
  • Deer*
  • Drug Interactions
  • Female
  • Hypertension / chemically induced
  • Hypertension / prevention & control
  • Hypertension / veterinary
  • Male
  • Medetomidine* / adverse effects
  • Quinolizines / pharmacology*
  • Tiletamine* / adverse effects
  • Zolazepam* / adverse effects

Substances

  • Anesthetics, Combined
  • Anesthetics, Intravenous
  • Quinolizines
  • Tiletamine
  • vatinoxan
  • Zolazepam
  • Medetomidine