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PloS one2020; 15(4); e0224720; doi: 10.1371/journal.pone.0224720

Ischaemic preconditioning and pharmacological preconditioning with dexmedetomidine in an equine model of small intestinal ischaemia-reperfusion.

Abstract: Small intestinal strangulation associated with ischaemia-reperfusion injury (IRI) is common in horses. In laboratory animals IRI can be ameliorated by ischaemic preconditioning (IPC) and pharmacological preconditioning (PPC) with dexmedetomidine. The aim of this study was to determine the effect of PPC with dexmedetomidine or IPC in an equine model of small intestinal ischaemia-reperfusion (IR). In a randomized controlled experimental trial, 15 horses were assigned to three groups: control (C), IPC, and PPC with dexmedetomidine (DEX). All horses were placed under general anaesthesia and 90% jejunal ischaemia was induced for 90 minutes, followed 30 minutes of reperfusion. In group IPC, three short bouts of ischaemia and reperfusion were implemented, and group DEX received a continuous rate infusion of dexmedetomidine prior to the main ischaemia. Jejunal biopsies were collected before ischaemia (P), and at the end of ischaemia (I) and reperfusion (R). Mucosal injury was assessed by the Chiu-Score, inflammatory cells were stained by cytosolic calprotectin. The degree of apoptosis and cell necrosis was assessed by cleaved-caspase-3 and TUNEL. Parametric data were analyzed by two-way ANOVA for repeated measurements followed by Dunnetts t-test. Non parametric data were compared between groups at the different time points by a Kruskal-Wallis-Test and a Wilcoxon-2-Sample-test. The mucosal injury score increased during I in all groups. After reperfusion, IRI further progressed in group C, but not in IPC and DEX. In all groups the number of cleaved caspase-3 and TUNEL positive cells increased from P to I. The number of TUNEL positive cells were lower in group DEX compared to group C after I and R. Infiltration with calprotectin positive cells was less pronounced in group DEX compared to group C, whereas in group IPC more calprotectin positive cells were seen. In conclusion, IPC and DEX exert protective effects in experimental small intestinal ischaemia in horses.
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Publication Date: 2020-04-29 PubMed ID: 32348301PubMed Central: PMC7190151DOI: 10.1371/journal.pone.0224720Google Scholar: Lookup
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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.

This study examines the impact of pharmacological preconditioning (PPC) with dexmedetomidine and ischemic preconditioning (IPC) in reducing ischaemia-reperfusion injury (IRI), often associated with small intestinal strangulation in horses. The research concludes that both IPC and PPC with dexmedetomidine exert a protective effect in experimental small intestinal ischaemia in horses.

Research Methodology

  • The study is a randomized controlled experimental trial conducted on 15 horses, divided into three groups – control (C), IPC, and PPC with dexmedetomidine (DEX).
  • Ischaemia for all horses was induced in the same surgical procedure under general anaesthesia.
  • The groups underwent three short bouts of ischaemia and reperfusion in IPC and received a continuous rate infusion of dexmedetomidine prior to the main ischaemia in the DEX group.
  • Jejunal biopsies were taken before ischaemia (P), at the end of ischaemia (I), and after reperfusion (R).
  • Various biomarkers were studied including cleaved-caspase-3 and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) for assessing apoptosis and cell necrosis, cytosolic calprotectin for staining inflammatory cells, and the Chiu-Score for assessing mucosal injury.

Results and Findings

  • All groups showed an increase in the mucosal injury score during I.
  • Post-reperfusion, the mucosal injury continued in the control group but not in the IPC and DEX groups, indicating the protective effects.
  • All groups had an increased number of cleaved caspase-3 and TUNEL positive cells from P to I.
  • The TUNEL positive cells were fewer in the DEX group compared to the control group post-I and R, suggesting the protective role of dexmedetomidine.
  • Group DEX showed less infiltration of calprotectin positive cells compared to the control group, while the IPC group had more calprotectin positive cells.

Conclusion

  • The study concludes that both IPC and PPC with dexmedetomidine offer a level of protection against ischaemia-reperfusion injury in horses.
  • It highlights the potential use of these procedures to manage or prevent small intestinal strangulation associated with IRI in horses.

Cite This Article

APA
König KS, Verhaar N, Hopster K, Pfarrer C, Neudeck S, Rohn K, Kästner SBR. (2020). Ischaemic preconditioning and pharmacological preconditioning with dexmedetomidine in an equine model of small intestinal ischaemia-reperfusion. PLoS One, 15(4), e0224720. https://doi.org/10.1371/journal.pone.0224720

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 15
Issue: 4
Pages: e0224720
PII: e0224720

Researcher Affiliations

König, Kathrin S
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
Verhaar, Nicole
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
Hopster, Klaus
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
Pfarrer, Christiane
  • Institute for Anatomy, University of Veterinary Medicine Hannover, Hannover, Germany.
Neudeck, Stephan
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
Rohn, Karl
  • Department of Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Hannover, Germany.
Kästner, Sabine B R
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
  • Clinic for Small Animals, University of Veterinary Medicine Hannover, Hannover, Germany.

MeSH Terms

  • Adrenergic alpha-2 Receptor Agonists / administration & dosage
  • Adrenergic alpha-2 Receptor Agonists / pharmacology
  • Adrenergic alpha-2 Receptor Agonists / therapeutic use
  • Animals
  • Dexmedetomidine / administration & dosage
  • Dexmedetomidine / pharmacology
  • Dexmedetomidine / therapeutic use
  • Horses
  • Ischemia / drug therapy
  • Ischemia / therapy
  • Ischemic Preconditioning / methods
  • Jejunum / blood supply
  • Jejunum / drug effects
  • Jejunum / pathology
  • Random Allocation
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / therapy

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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Citations

This article has been cited 5 times.
  1. 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).
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  2. 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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  5. 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).
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