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Equine veterinary journal2019; 51(5); 646-652; doi: 10.1111/evj.13085

Effects of vatinoxan on cardiorespiratory function and gastrointestinal motility during constant-rate medetomidine infusion in standing horses.

Abstract: Medetomidine suppresses cardiovascular function and reduces gastrointestinal motility in horses mainly through peripheral α -adrenoceptors. Vatinoxan, a peripheral α -antagonist, has been shown experimentally to alleviate the adverse effects of some α -agonists in horses. However, vatinoxan has not been investigated during constant-rate infusion (CRI) of medetomidine in standing horses. Objective: To evaluate effects of vatinoxan on cardiovascular function, gastrointestinal motility and on sedation level during CRI of medetomidine. Methods: Experimental, randomised, blinded, cross-over study. Methods: Six healthy horses were given medetomidine hydrochloride, 7 μg/kg i.v., without (MED) and with (MED+V) vatinoxan hydrochloride, 140 μg/kg i.v., followed by CRI of medetomidine at 3.5 μg/kg/h for 60 min. Cardiorespiratory variables were recorded and borborygmi and sedation levels were scored for 120 min. Plasma drug concentrations were measured. The data were analysed using repeated measures ANCOVA and paired t-tests as appropriate. Results: Initially heart rate (HR) was significantly lower and mean arterial blood pressure (MAP) significantly higher with MED compared with MED+V. For example at 10 min HR (mean ± s.d.) was 26 ± 2 and 31 ± 5 beats/minute (P = 0.04) and MAP 129 ± 15 and 103 ± 13 mmHg (P<0.001) respectively. At 10 min, cardiac index was lower (P = 0.02) and systemic vascular resistance higher (P = 0.001) with MED than with MED+V. Borborygmi were reduced after MED; this effect was attenuated by vatinoxan (P<0.001). All horses were sedated with medetomidine, but the mean sedation scores were reduced with MED+V until 20 min (6.8 ± 0.8 and 4.5 ± 1.5 with MED and MED+V, respectively, at 10 min, P = 0.001). Plasma concentration of dexmedetomidine was significantly lower in the presence of vatinoxan (P = 0.01). Conclusions: Experimental study with healthy, unstimulated animals. Conclusions: Vatinoxan administered i.v. with a loading dose of medetomidine improved cardiovascular function and gastrointestinal motility during medetomidine CRI in healthy horses. Sedation was slightly yet significantly reduced during the first 20 min.. The Summary is available in Portuguese - see Supporting Information.
© 2019 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2019-03-14 PubMed ID: 30793362PubMed Central: PMC6767159DOI: 10.1111/evj.13085Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research examines the impact of vatinoxan, an alpha antagonist, on medetomidine-induced cardiorespiratory and gastrointestinal effects in horses. The study concluded that vatinoxan improved both cardiovascular function and gut movement during a medetomidine infusion in horses, although it slightly reduced sedation levels in the initial 20 minutes.

Study Design and Methodology:

  • Six healthy horses were used for this experiment, which was a randomised, blinded, cross-over style study.
  • Each horse received an intravenous injection (i.v) of medetomidine hydrochloride, either alone (referred to as MED) or with vatinoxan hydrochloride (referred to as MED+V).
  • A constant-rate infusion (CRI) of medetomidine was administered to the horses for 60 minutes.
  • Over a period of 120 minutes, several variables were measured including cardiorespiratory variables, borborygmi (stomach sounds, indicating gut movement), and sedation levels.
  • Plasma drug concentrations were also measured, and the data collected was analysed using repeated measures ANCOVA and paired t-tests.

Key Findings:

  • Initial heart rate was notably lower, and mean arterial blood pressure significantly higher in the MED group compared to the MED+V group.
  • At 10 minutes, the cardiac index (measure of cardiac performance) was lower, while systemic vascular resistance (a measure of blood flow resistance) was higher in MED administered horses than in MED+V group.
  • Medetomidine administration resulted in reduced borborygmi, indicative of lowered gastrointestinal activity; this effect was less pronounced when the horses were also given vatinoxan.
  • All horses were sedated as a result of the medetomidine. However, the sedation levels were reduced more quickly in the MED+V group, noticeable within the first 20 minutes.
  • The presence of vatinoxan resulted in a lower plasma concentration of dexmedetomidine, a more potent isomer of medetomidine.

Conclusion:

  • The research confirmed that combined administration of vatinoxan with medetomidine in healthy horses improved both cardiovascular function and gastrointestinal motility during a medetomidine infusion.
  • However, it should be noted that these findings were based on healthy, unstimulated animals. Further research might be useful to understand if the same effects are observed in horses under different health conditions and stimuli.

Cite This Article

APA
Tapio H, Raekallio MR, Mykkänen A, Männikkö S, Scheinin M, Bennett RC, Vainio O. (2019). Effects of vatinoxan on cardiorespiratory function and gastrointestinal motility during constant-rate medetomidine infusion in standing horses. Equine Vet J, 51(5), 646-652. https://doi.org/10.1111/evj.13085

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 51
Issue: 5
Pages: 646-652

Researcher Affiliations

Tapio, H
  • Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
Raekallio, M R
  • Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
Mykkänen, A
  • Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
Männikkö, S
  • 4Pharma Ltd., Turku, Finland.
Scheinin, M
  • Institute of Biomedicine, University of Turku, Turku, Finland.
  • Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.
Bennett, R C
  • Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
Vainio, O
  • Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.

MeSH Terms

  • Animals
  • Area Under Curve
  • Cross-Over Studies
  • Female
  • Gastrointestinal Motility / drug effects
  • Half-Life
  • Heart Rate / drug effects
  • Horses
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / pharmacology
  • Male
  • Medetomidine / metabolism
  • Medetomidine / pharmacokinetics
  • Medetomidine / pharmacology
  • Quinolizines / administration & dosage
  • Quinolizines / pharmacology
  • Respiration / drug effects
  • Vascular Resistance / drug effects

Grant Funding

  • Vetcare Ltd.

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Citations

This article has been cited 6 times.
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