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Home / Equine Research Bank / Equine Vet J / Protective effects of dexmedetomidine on small intestinal is...
Equine veterinary journal2020; 53(3); 569-578; doi: 10.1111/evj.13337

Protective effects of dexmedetomidine on small intestinal ischaemia-reperfusion injury in horses.

Abstract: Strangulating small intestinal lesions in the horse have increased morbidity and mortality compared to nonstrangulating obstructions due to mucosal barrier disruption and subsequent endotoxaemia. Objective: To investigate protective effects of dexmedetomidine on small intestinal ischaemia-reperfusion injury in the horse. Methods: Randomised, controlled, experimental study. Methods: Eighteen systemically healthy horses were randomly assigned to three groups: control, preconditioning, and post-conditioning. During isoflurane anaesthesia, complete ischaemia was induced in a 1-m segment of jejunum for 90 minutes. Horses in the preconditioning and post-conditioning groups received dexmedetomidine (3.5 µg/kg followed by 7 µg/kg/h) before (preconditioning) or after beginning ischaemia (post-conditioning), and during reperfusion. Jejunal biopsies were collected before ischaemia (baseline-1), at the end of the ischaemic period (ischaemia), and 30 minutes after reperfusion (reperfusion-1). Additional biopsies were taken 24 hours after reperfusion from ischaemia-reperfusion-injured jejunum (reperfusion-2). Epithelial injury was scored histologically, and morphometric analyses were used to calculate villus surface area (VSA) denuded of epithelium. Data were analysed using analysis of variance, Kruskal-Wallis and Wilcoxon two-sample tests. Results: In the control group, epithelial injury scores and percentage of VSA denudation for ischaemia-reperfusion-injured jejunum were higher compared to baseline-1 at all time points. The ischaemia and both reperfusion samples from the pre- and post-conditioning groups had lower epithelial injury scores and percentage of VSA epithelial denudation compared to the control group, with no difference from baseline-1 at any time point for the preconditioning group. Conclusions: Preconditioning has limited application in the clinical setting with naturally occurring strangulating small intestinal lesions. Conclusions: Dexmedetomidine was protective for small intestinal ischaemia-reperfusion injury in the horse when administered before or during ischaemia.
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Publication Date: 2020-09-17 PubMed ID: 32862437DOI: 10.1111/evj.13337Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

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This study aimed to investigate the protective effects of dexmedetomidine in horses on intestinal injuries caused by ischaemia-reperfusion, a condition where blood supply returns to the tissue after a period of ischaemia or lack of oxygen. It found that horses treated with dexmedetomidine before or during the ischaemic event had less damage compared to those who did not receive the treatment.

Research Methodology

  • This study was a randomized, controlled, and experimental trial that included eighteen healthy horses, which were randomly assigned to one of three groups: control, preconditioning, and post-conditioning.
  • A segment of the horse’s jejunum, a section of the small intestine, was subjected to complete ischaemia for 90 minutes. This process was administered under isoflurane anaesthesia.
  • Horses in the preconditioning and post-conditioning groups received dexmedetomidine, a medication commonly used as a sedative or analgesic. The doses were administered before (preconditioning group) or after beginning ischaemia (post-conditioning group) and during reperfusion—the process of restoring blood flow to the tissue.
  • Jejunal biopsies were taken from the horses at various points: before ischaemia (baseline-1), at the end of the ischaemic period (ischaemia), and 30 minutes after reperfusion (reperfusion-1). Another biopsy was also taken 24 hours after reperfusion from the ischaemia-reperfusion-injured jejunum (reperfusion-2).
  • The evaluation of epithelial injury, which is the damage to the tissue lining the jejunum, was scored histologically and the proportion of villus surface area (VSA) that was stripped of epithelium—the outer layer of cells—was calculated using morphometric analyses.

Key Findings

  • The control group, which did not receive dexmedetomidine, demonstrated increased histological injury scores and a greater proportion of VSA denudation in the post-ischaemia reperfusion-injured tile of jejunum compared to the baseline measurement.
  • The ischaemic and reperfusion samples from the groups that received dexmedetomidine (pre- and post-conditioning groups) showed reduced epithelial injury scores and less VSA epithelial denudation compared to the control group. In fact, the preconditioning group showed no difference from baseline-1 at any time point, signalling the protective effects of dexmedetomidine.

Conclusion

  • The authors suggest that while preconditioning using dexmedetomidine has limited use in clinical settings due to its requirement of anticipation of the ischaemic event, the drug demonstrates protective effects against small-intestinal ischaemia-reperfusion injury in horses when administered either before or during the ischaemic event.

Cite This Article

APA
VanderBroek AR, Engiles JB, Kästner SBR, Kopp V, Verhaar N, Hopster K. (2020). Protective effects of dexmedetomidine on small intestinal ischaemia-reperfusion injury in horses. Equine Vet J, 53(3), 569-578. https://doi.org/10.1111/evj.13337

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 53
Issue: 3
Pages: 569-578

Researcher Affiliations

VanderBroek, Ashley R
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
Engiles, Julie B
  • Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.
Kästner, Sabine B R
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Kopp, Veronika
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Verhaar, Nicole
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Hopster, Klaus
  • Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.

MeSH Terms

  • Animals
  • Dexmedetomidine / pharmacology
  • Horse Diseases / prevention & control
  • Horses
  • Intestinal Mucosa
  • Intestine, Small
  • Jejunum
  • Reperfusion Injury / prevention & control
  • Reperfusion Injury / veterinary

Grant Funding

  • University of Pennsylvania

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Citations

This article has been cited 6 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. Zhan Y, Chen Z, Qiu Y, Deng Q, Huang W, Wen S, Shen J. DEXMEDETOMIDINE PREVENTS PDIA3 DECREASE BY ACTIVATING α2-ADRENERGIC RECEPTOR TO ALLEVIATE INTESTINAL I/R IN MICE.. Shock 2022 Dec 1;58(6):556-564.
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  4. Dengler F, Sternberg F, Grages M, Kästner SB, Verhaar N. Adaptive mechanisms in no flow vs. low flow ischemia in equine jejunum epithelium: Different paths to the same destination.. Front Vet Sci 2022;9:947482.
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