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Veterinary anaesthesia and analgesia2017; 45(2); 165-174; doi: 10.1016/j.vaa.2017.08.010

Effect of dexmedetomidine and xylazine followed by MK-467 on gastrointestinal microperfusion in anaesthetized horses.

Abstract: To compare the effects of MK-467 during isoflurane anaesthesia combined with xylazine or dexmedetomidine on global and gastrointestinal perfusion parameters. Methods: Prospective, randomized experimental trial. Methods: A total of 15 warmblood horses. Methods: Horses were divided into two groups for administration of either dexmedetomidine (D) or xylazine (X) for premedication (D: 3.5 μg kg; X: 0.5 mg kg) and as constant rate infusion during isoflurane anaesthesia (D: 7 μg kg hour; X: 1 mg kg hour). During anaesthesia, heart rate, mean arterial blood pressure (MAP), systemic vascular resistance index (SVRI) and cardiac index (CI) were measured. Microperfusion of the colon, jejunum and stomach was measured using laser Doppler flowmetry. After 2 hours of stabilization, MK-467 (250 μg kg) was administered, and measurements were continued for another 90 minutes. For statistical analysis, the permutation test and Wilcoxon rank-sum test were used (p < 0.05). Results: There were no differences in baseline measurements between groups. The MK-467 bolus resulted in a significant decrease in MAP (D: -58%; X: -48%) and SVRI (D: -68%; X: -65%) lasting longer in group D (90 minutes) compared to group X (60 minutes). While CI increased (D: +31%; X: +35%), microperfusion was reduced in the colon (D: -44%; X: -34%), jejunum (D: -26%; X: -33%) and stomach (D: -37%; X: -35%). Conclusions: Alpha-2-agonist induced vasoconstriction was reversed by the MK-467 dose used, resulting in hypotension and rise in CI. Gastrointestinal microperfusion decreased, probably as a result of insufficient perfusion pressure. An infusion rate for MK-467 as well as an ideal agonist/antagonist ratio should be determined.
Publication Date: 2017-09-15 PubMed ID: 29439859DOI: 10.1016/j.vaa.2017.08.010Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Randomized Controlled Trial

Summary

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The study investigates the impact of MK-467 on horses in combination with isoflurane anaesthesia and either xylazine or dexmedetomidine. The results suggest MK-467 reduces arterial blood pressure and systemic vascular resistance but increases cardiac index and decreases gastrointestinal microperfusion, likely due to inadequate perfusion pressure.

Methodology and Approach

  • The research conducted was a prospective, randomized experimental trial involving 15 warmblood horses.
  • The horses were split into two groups to receive either dexmedetomidine or xylazine for premedication, and as a constant rate infusion during isoflurane anaesthesia.
  • Various health parameters were measured during anaesthesia, including heart rate, mean arterial blood pressure (MAP), systemic vascular resistance index (SVRI), and cardiac index (CI). The authors also observed microperfusion in the colon, jejunum, and stomach using laser Doppler flowmetry.
  • Following 2 hours of stabilization, the horses were administered MK-467, and the mentioned parameters were measured for an additional 90 minutes.

Findings

  • No differences were noted in the baseline measurements between the two groups.
  • Administration of MK-467 resulted in a significant decrease in MAP and SVRI in both groups, with the effects lasting longer in the dexmedetomidine group.
  • Despite an increased CI in both groups, the study found a decrease in microperfusion in the colon, jejunum, and stomach.
  • The results suggest that the vasoconstriction induced by alpha-2-agonist was reversed by the administered dose of MK-467, leading to hypotension and an increase in CI. However, the gastrointestinal microperfusion years decreased, probably due to insufficient perfusion pressure.

Conclusions and Further Research

  • The study concludes that the MK-467 dosage used reversed alpha-2-agonist vasoconstriction, causing a rise in CI and hypotension.
  • The resulting decrease in gastrointestinal microperfusion indicates that insufficient perfusion pressure may be a side effect of this treatment strategy.
  • The research suggests the need to determine an infusion rate for MK-467, as well as the ideal ratio between agonist and antagonist.

Cite This Article

APA
Wittenberg-Voges L, Kästner SB, Raekallio M, Vainio OM, Rohn K, Hopster K. (2017). Effect of dexmedetomidine and xylazine followed by MK-467 on gastrointestinal microperfusion in anaesthetized horses. Vet Anaesth Analg, 45(2), 165-174. https://doi.org/10.1016/j.vaa.2017.08.010

Publication

ISSN: 1467-2995
NlmUniqueID: 100956422
Country: United States
Language: English
Volume: 45
Issue: 2
Pages: 165-174
PII: S1467-2987(17)30349-5

Researcher Affiliations

Wittenberg-Voges, Liza
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hanover, Germany. Electronic address: liza.wittenberg@googlemail.com.
Kästner, Sabine Br
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hanover, Germany.
Raekallio, Marja
  • University of Helsinki, Faculty of Veterinary Medicine, Helsinki, Finland.
Vainio, Outi M
  • University of Helsinki, Faculty of Veterinary Medicine, Helsinki, Finland.
Rohn, Karl
  • Department of Biometry, University of Veterinary Medicine Hannover, Hanover, Germany.
Hopster, Klaus
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hanover, Germany.

MeSH Terms

  • Adrenergic alpha-2 Receptor Agonists / pharmacology
  • Anesthesia / veterinary
  • Anesthetics, Combined
  • Animals
  • Dexmedetomidine / pharmacology
  • Female
  • Gastrointestinal Tract / blood supply
  • Gastrointestinal Tract / drug effects
  • Horses
  • Isoflurane / administration & dosage
  • Male
  • Microcirculation / drug effects
  • Oxygen / metabolism
  • Prospective Studies
  • Quinolizines / pharmacology
  • Xylazine / pharmacology

Citations

This article has been cited 3 times.
  1. Verhaar N, Kopp V, Pfarrer C, Neudeck S, König K, Rohn K, Kästner S. Alpha(2) Antagonist Vatinoxan Does Not Abolish the Preconditioning Effect of Dexmedetomidine on Experimental Ischaemia-Reperfusion Injury in the Equine Small Intestine.. Animals (Basel) 2023 Aug 30;13(17).
    doi: 10.3390/ani13172755pubmed: 37685019google scholar: lookup
  2. Verhaar N, Hoppe S, Grages AM, Hansen K, Neudeck S, Kästner S, Mazzuoli-Weber G. Dexmedetomidine Has Differential Effects on the Contractility of Equine Jejunal Smooth Muscle Layers In Vitro.. Animals (Basel) 2023 Mar 10;13(6).
    doi: 10.3390/ani13061021pubmed: 36978562google scholar: lookup
  3. König KS, Verhaar N, Hopster K, Pfarrer C, Neudeck S, Rohn K, Kästner SBR. Ischaemic preconditioning and pharmacological preconditioning with dexmedetomidine in an equine model of small intestinal ischaemia-reperfusion.. PLoS One 2020;15(4):e0224720.
    doi: 10.1371/journal.pone.0224720pubmed: 32348301google scholar: lookup