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Equine veterinary journal2021; 54(2); 427-437; doi: 10.1111/evj.13450

The effect of ischaemic postconditioning on mucosal integrity and function in equine jejunal ischaemia.

Abstract: Ischaemic postconditioning (IPoC) has been shown to ameliorate ischaemia reperfusion injury in different species and tissues. Objective: To assess the feasibility of IPoC in equine small intestinal ischaemia and to assess its effect on histomorphology, electrophysiology and paracellular permeability. Methods: Randomised in vivo experiment. Methods: Experimental jejunal ischaemia was induced for 90 min in horses under general anaesthesia. In the control group (C; n = 7), the jejunum was reperfused without further intervention. In the postconditioning group (IPoC; n = 7), reocclusion was implemented following release of ischaemia by clamping the mesenteric vessels in three cycles of 30 seconds. This was followed by 120 minutes of reperfusion in both groups. Intestinal microperfusion and oxygenation was measured during IPoC using spectrophotometry and Doppler flowmetry. Histomorphology and histomorphometry of the intestinal mucosa were assessed. Furthermore, electrophysiological variables and unidirectional flux rates of H-mannitol were determined in Ussing chambers. Western blot analysis was performed to determine the tight junction protein levels of claudin-1, claudin-2 and occludin in the intestinal mucosa. Comparisons between the groups and time points were performed using a two-way repeated measures analysis of variance (ANOVA) or non-parametric statistical tests for the ordinal and not normally distributed data (significance P < .05). Results: IPoC significantly reduced intestinal microperfusion during all clamping cycles yet affected oxygen saturation only during the first cycle. After reperfusion, Group IPoC showed significantly less mucosal villus denudation (mean difference 21.5%, P = .02) and decreased mucosal-to-serosal flux rates (mean difference 15.2 nM/cm /h, P = .007) compared to Group C. There were no significant differences between the groups for the other tested variables. Conclusions: Small sample size, long-term effects were not investigated. Conclusions: Following IPoC, the intestinal mucosa demonstrated significantly less villus denudation and paracellular permeability compared to the untreated control group, possibly indicating a protective effect of IPoC on ischaemia reperfusion injury.
Publication Date: 2021-05-18 PubMed ID: 34003501DOI: 10.1111/evj.13450Google Scholar: Lookup
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  • Journal Article

Summary

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The research investigates whether ischaemic postconditioning (IPOC), a technique of controlled reperfusion, can alleviate the detrimental impacts of ischaemia reperfusion injury in the small intestine of horses. The authors demonstrate that IPOC can considerably minimize intestinal villus denudation and paracellular permeability, suggesting its potential protective role against ischaemia reperfusion injury.

Methodology of the Research

  • The study’s design was a randomised in vivo experiment.
  • Jejunal ischaemia, a condition where the small intestine’s blood supply is blocked, was experimentally induced in horses under general anaesthesia for 90 minutes.
  • Two groups were designated: the control group (Group C) where the jejunum was allowed reperfusion without any further intervention, and the ischaemic postconditioning group (Group IPoC).
  • In Group IPoC, a process of controlled reperfusion (IPOC) was implemented, involving re-occlusion by clamping the mesenteric vessels in three cycles of 30 seconds each.
  • In both groups, this was followed by 120 minutes of reperfusion.
  • Intestinal microperfusion and oxygenation were measured during IPoC using spectrophotometry and Doppler flowmetry.
  • Microscopic examination of the intestinal mucosa was performed to check any changes in its structure and density (histomorphology and histomorphometry).
  • The study also involved measuring variables of electrophysiology and the unidirectional flux rates of H-mannitol in Ussing chambers.
  • Western blot analysis was conducted to determine the level of tight junction proteins (claudin-1, claudin-2, and occludin) in the intestinal mucosa.
  • A two-way repeated measures analysis of variance (ANOVA) or non-parametric statistical tests were used for comparisons between the groups and timepoints.

Results of the Research

  • IPoC significantly reduced intestinal microperfusion during all clamping cycles and affected oxygen saturation only during the first cycle.
  • The IPoC group showed significantly less mucosal villus denudation and decreased mucosal-to-serosal flux rates compared to the control group.
  • No significant differences were noted between the two groups for other tested variables.

Implications and Limitations

  • The study suggests that IPoC may play a protective role against ischaemia reperfusion injury by minimizing damage to the intestinal villus and reducing paracellular permeability.
  • However, this research was limited by a small sample size and did not explore the long-term effects of IPoC.

Cite This Article

APA
Verhaar N, Breves G, Hewicker-Trautwein M, Pfarrer C, Rohn K, Burmester M, Schnepel N, Neudeck S, Twele L, Kästner S. (2021). The effect of ischaemic postconditioning on mucosal integrity and function in equine jejunal ischaemia. Equine Vet J, 54(2), 427-437. https://doi.org/10.1111/evj.13450

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 54
Issue: 2
Pages: 427-437

Researcher Affiliations

Verhaar, Nicole
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
Breves, Gerhard
  • Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hannover, Germany.
Hewicker-Trautwein, Marion
  • Institute for Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
Pfarrer, Christiane
  • Institute for Anatomy, University of Veterinary Medicine Hannover, Hannover, Germany.
Rohn, Karl
  • Institute for Biometry and Epidemiology, University of Veterinary Medicine Hannover, Hannover, Germany.
Burmester, Marion
  • Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hannover, Germany.
Schnepel, Nadine
  • Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hannover, Germany.
Neudeck, Stephan
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
Twele, Lara
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
Kästner, Sabine
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
  • Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover, Germany.

MeSH Terms

  • Animals
  • Horse Diseases / prevention & control
  • Horses
  • Intestine, Small
  • Ischemia / veterinary
  • Ischemic Postconditioning / veterinary
  • Jejunum
  • Reperfusion Injury / prevention & control
  • Reperfusion Injury / veterinary

Grant Funding

  • (Residency Research Grant) / European College of Veterinary Surgeons
  • Stiftung Pro Pferd

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Citations

This article has been cited 6 times.
  1. Verhaar N, de Buhr N, von Köckritz-Blickwede M, Dümmer K, Hewicker-Trautwein M, Pfarrer C, Dengler F, Kästner S. Hypoxia signaling in the equine small intestine: Expression and distribution of hypoxia inducible factors during experimental ischemia. Front Vet Sci 2023;10:1110019.
    doi: 10.3389/fvets.2023.1110019pubmed: 36908508google scholar: lookup
  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.
    doi: 10.3389/fvets.2022.947482pubmed: 36157182google scholar: lookup
  3. Grages AM, Verhaar N, Pfarrer C, Breves G, Burmester M, Neudeck S, Kästner S. Low Flow versus No Flow: Ischaemia Reperfusion Injury Following Different Experimental Models in the Equine Small Intestine. Animals (Basel) 2022 Aug 22;12(16).
    doi: 10.3390/ani12162158pubmed: 36009747google scholar: lookup
  4. Sengul I, Sengul D. Clinical Insights on Pre- and Novel Postconditioning in Equine Jejunal Ischemia. Med Arch 2021 Jun;75(3):237-238.
  5. Guo Q, Wang J, Ni C, Pan J, Zou J, Shi Y, Sun J, Zhang X, Wang D, Luan F. Research progress on the natural products in the intervention of myocardial infarction. Front Pharmacol 2024;15:1445349.
    doi: 10.3389/fphar.2024.1445349pubmed: 39239656google scholar: lookup
  6. Verhaar N, de Buhr N, von Köckritz-Blickwede M, Hewicker-Trautwein M, Pfarrer C, Mazzuoli-Weber G, Schulte H, Kästner S. Ischaemic postconditioning reduces apoptosis in experimental jejunal ischaemia in horses. BMC Vet Res 2021 Apr 26;17(1):175.
    doi: 10.1186/s12917-021-02877-ypubmed: 33902575google scholar: lookup