Analyze Diet
Animals : an open access journal from MDPI2022; 12(16); doi: 10.3390/ani12162158

Low Flow versus No Flow: Ischaemia Reperfusion Injury Following Different Experimental Models in the Equine Small Intestine.

Abstract: In experimental studies investigating strangulating intestinal lesions in horses, different ischaemia models have been used with diverging results. Therefore, the aim was to comparatively describe ischaemia reperfusion injury (IRI) in a low flow (LF) and no flow (NF) model. Under general anaesthesia, 120 min of jejunal ischaemia followed by 120 min of reperfusion was induced in 14 warmbloods. During ischaemia, blood flow was reduced by 80% (LF, n = 7) or by 100% (NF, n = 7). Intestinal blood flow and oxygen saturation were measured by Laser Doppler fluxmetry and spectrophotometry. Clinical, histological, immunohistochemical and Ussing chamber analyses were performed on intestinal samples collected hourly. Tissue oxygen saturation was significantly lower in NF ischaemia. The LF group exhibited high variability in oxygen saturation and mucosal damage. Histologically, more haemorrhage was found in the LF group at all time points. Cleaved-caspase-3 and calprotectin-stained cells increased during reperfusion in both groups. After NF ischaemia, the tissue conductance was significantly higher during reperfusion. These results aid in the selection of suitable experimental models for future studies. Although the LF model has been suggested to be more representative for clinical strangulating small intestinal disease, the NF model produced more consistent IRI.
Publication Date: 2022-08-22 PubMed ID: 36009747PubMed Central: PMC9405230DOI: 10.3390/ani12162158Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

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 research compares the effects of low flow (LF) and no flow (NF) ischemia models on intestinal reperfusion injury (IRI) in horses. It finds that while LF models cause more injury variance, NF models consistently produce significant IRI.

Introduction and Objectives

  • The study’s goal was to compare and describe ischemia reperfusion injury (IRI), a type of harm to the digestive system due to a lack or reduction of blood flow, in a low flow (LF) and no flow (NF) model. This was done using horses as the test subject.
  • The LF model reduces blood flow by 80%, while the NF model stops blood completely.

Methodology

  • Under general anesthesia, ischemia was induced for 120 minutes followed by 120 minutes of reperfusion in 14 warmblood horses.
  • A wide variety of measurements and analyses were conducted, such as intestinal blood flow and oxygen saturation were evaluated using Laser Doppler fluxmetry and spectrophotometry.
  • Additional testings, such as clinical, histological, immunohistochemical and Ussing chamber analyses, were also performed on intestinal samples collected every hour.

Findings

  • Tissue oxygen saturation was significantly lower during NF ischemia.
  • The LF group presented high variability in oxygen saturation and mucosal damage.
  • In relation to histological damages, more haemorrhaging was observed in the LF group at all time points.
  • Markers of cell death and inflammation, cleaved-caspase-3 and calprotectin-stained cells, increased during reperfusion in both groups.
  • After NF ischemia, the intestinal tissue’s conductance was significantly higher during reperfusion which is evidence of more consistent ischemia reperfusion injury (IRI).

Implications

  • The results from this study can assist in choosing the best experimental model for future research into intestinal ischemic conditions.
  • While the LF model has been considered more representative for clinical strangulating small intestinal disease, the information presented seems to suggest that the NF model may offer a more consistent and predictable ischemia-reperfusion injury (IRI) setup.

Cite This Article

APA
Grages AM, Verhaar N, Pfarrer C, Breves G, Burmester M, Neudeck S, Kästner S. (2022). Low Flow versus No Flow: Ischaemia Reperfusion Injury Following Different Experimental Models in the Equine Small Intestine. Animals (Basel), 12(16). https://doi.org/10.3390/ani12162158

Publication

ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 12
Issue: 16

Researcher Affiliations

Grages, Anna Marei
  • Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Verhaar, Nicole
  • Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Pfarrer, Christiane
  • Institute for Anatomy, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Breves, Gerhard
  • Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Burmester, Marion
  • Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Neudeck, Stephan
  • Small Animal Clinic, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Kästner, Sabine
  • Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
  • Small Animal Clinic, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 28 references
  1. Rowe EL, White NA, Buechner-Maxwell V, Robertson JL, Ward DL. Detection of apoptotic cells in intestines from horses with and without gastrointestinal tract disease.. Am. J. Vet. Res. 2003;64:982–988.
    doi: 10.2460/ajvr.2003.64.982pubmed: 12926589google scholar: lookup
  2. Mair TS, Smith LJ. Survival and complication rates in 300 horses undergoing surgical treatment of colic. Part 3: Short-term complications.. Equine Vet. J. 2005;37:303–309.
    doi: 10.2746/0425164054529364pubmed: 16028617google scholar: lookup
  3. Laws EG, Freeman DE. Significance of reperfusion injury after venous strangulation obstruction of equine jejunum.. J. Investig. Surg. 1995;8:263–270.
    doi: 10.3109/08941939509031600pubmed: 8519742google scholar: lookup
  4. Dabareiner RM, Sullins KE, White NA, Snyder JR. Serosal injury in the equine jejunum and ascending colon after ischemia-reperfusion or intraluminal distention and decompression.. Vet. Surg. 2001;30:114–125.
    doi: 10.1053/jvet.2001.21393pubmed: 11230765google scholar: lookup
  5. 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:e0224720.
  6. Verhaar N, Breves G, Hewicker-Trautwein M, Pfarrer C, Rohn K, Burmester M, Schnepel N, Neudeck S, Twele L, Kästner SBR. The effect of ischaemic postconditioning on mucosal integrity and function in equine jejunal ischaemia.. Equine Vet. J. 2021;54:427–437.
    doi: 10.1111/evj.13450pubmed: 34003501google scholar: lookup
  7. 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;17:175.
    doi: 10.1186/s12917-021-02877-ypmc: PMC8077964pubmed: 33902575google scholar: lookup
  8. Horne M, Pascoe P, Ducharme N, Barker I, Grovum W. Attempts to Modify Reperfusion Injury of Equine Jejunal Mucosa Using Dimethylsulfoxide, Allopurinol, and Intraluminal Oxygen.. Vet. Surg. 1994;23:241–249.
  9. Vatistas N, Snyder J, Hildebrand S, Harmon F, Woliner M, Barry S, Nieto J, Henry P, Enos L, Magliano D. Effects of U-74389G, a novel 21-aminosteroid, on small intestinal ischemia and reperfusion injury in horses.. Am. J. Vet. Res. 1996;57:762–770.
    pubmed: 8723896
  10. Little D, Tomlinson JE, Blikslager AT. Post operative neutrophilic inflammation in equine small intestine after manipulation and ischaemia.. Equine Vet. J. 2005;37:329–335.
    doi: 10.2746/0425164054529472pubmed: 16028622google scholar: lookup
  11. VanderBroek AR, Engiles JB, Kästner SBR, Kopp V, Verhaar N, Hopster K. Protective effects of dexmedetomidine on small intestinal ischaemia-reperfusion injury in horses.. Equine Vet. J. 2020;53:569–578.
    doi: 10.1111/evj.13337pubmed: 32862437google scholar: lookup
  12. Vatistas N, Snyder J, Nieto J, Hildebrand S, Woliner M, Harmon F, Barry S, Drake C. Morphologic changes and xanthine oxidase activity in the equine jejunum during low flow ischemia and reperfusion.. Am. J. Vet. Res. 1998;59:772–776.
    pubmed: 9622750
  13. Dabareiner RM, White NA, Donaldson L. Evaluation of Carolina Rinse solution as a treatment for ischaemia reperfusion of the equine jejunum.. Equine Vet. J. 2003;35:642–646.
    doi: 10.2746/042516403775696302pubmed: 14649354google scholar: lookup
  14. Cook VL, Jones Shults J, McDowell M, Campbell NB, Davis JL, Blikslager AT. Attenuation of ischaemic injury in the equine jejunum by administration of systemic lidocaine.. Equine Vet. J. 2008;40:353–357.
    doi: 10.2746/042516408X293574pubmed: 18321812google scholar: lookup
  15. Verhaar N, Pfarrer C, Neudeck S, König K, Rohn K, Twele L, Kästner S. Preconditioning with lidocaine and xylazine in experimental equine jejunal ischaemia.. Equine Vet. J. 2020;53:125–133.
    doi: 10.1111/evj.13251pubmed: 32119148google scholar: lookup
  16. Prichard M, Ducharme NG, Wilkins PA, Erb HN, Butt M. Xanthine oxidase formation during experimental ischemia of the equine small intestine.. Can. J. Vet. Res. 1991;55:310–314.
    pmc: PMC1263475pubmed: 1790484
  17. Dabareiner R, Snyder J, White N, Pascoe J, Harmon F, Gardner I, Woliner M, Pinney D, Sullins K. Microvascular permeability and endothelial cell morphology associated with low-flow ischemia/reperfusion injury in the equine jejunum.. Am. J. Vet. Res. 1995;56:639–648.
    pubmed: 7661461
  18. Young BL, White NA, Donaldson LL, Dabareiner RM. Treatment of ischaemic jejunum with topical and intraluminal Carolina Rinse.. Equine Vet. J. 2002;34:469–474.
    doi: 10.2746/042516402776117755pubmed: 12358049google scholar: lookup
  19. Hilton H, Nieto JE, Moore PF, Harmon FA, Naydan DK, Snyder JR. Expression of cyclooxygenase genes in the jejunum of horses during low-flow ischemia and reperfusion.. Am. J. Vet. Res. 2011;72:681–686.
    doi: 10.2460/ajvr.72.5.681pubmed: 21529221google scholar: lookup
  20. Bauck AG, Grosche A, Morton AJ, Graham AS, Vickroy TW, Freeman DE. Effect of lidocaine on inflammation in equine jejunum subjected to manipulation only and remote to intestinal segments subjected to ischemia.. Am. J. Vet. Res. 2017;78:977–989.
    doi: 10.2460/ajvr.78.8.977pubmed: 28738006google scholar: lookup
  21. Gonzalez LM, Moeser AJ, Blikslager AT. Animal models of ischemia-reperfusion-induced intestinal injury: Progress and promise for translational research.. Am. J. Physiol.-Gastrointest. Liver Physiol. 2015;308:G63–G75.
    doi: 10.1152/ajpgi.00112.2013pmc: PMC4297854pubmed: 25414098google scholar: lookup
  22. Hellman S. Generation of equine enteroids and enteroid-derived 2D monolayers that are responsive to microbial mimics.. Vet. Res. 2021;52:108.
    doi: 10.1186/s13567-021-00976-0pmc: PMC8364015pubmed: 34391473google scholar: lookup
  23. Stieler Stewart A, Freund JM, Gonzalez LM. Advanced three-dimensional culture of equine intestinal epithelial stem cells.. Equine Vet. J. 2017;50:241–248.
    doi: 10.1111/evj.12734pmc: PMC5796842pubmed: 28792626google scholar: lookup
  24. Powell RH, Behnke MS. WRN conditioned media is sufficient for in vitro propagation of intestinal organoids from large farm and small companion animals.. Biol. Open. 2017;6:698–705.
    doi: 10.1242/bio.021717pmc: PMC5450310pubmed: 28347989google scholar: lookup
  25. Chiu C-J. Intestinal Mucosal Lesion in Low-Flow States.. Arch. Surg. 1970;101:478.
  26. Wagner A, Junginger J, Lemensieck F, Hewicker-Trautwein M. Immunohistochemical characterization of gastrointestinal macrophages/phagocytes in dogs with inflammatory bowel disease (IBD) and non-IBD dogs.. Vet. Immunol. Immunopathol. 2018;197:49–57.
    doi: 10.1016/j.vetimm.2018.01.011pubmed: 29475506google scholar: lookup
  27. Wilkens M, Marholt L, Eigendorf N, Muscher-Banse A, Feige K, Schröder B, Breves G, Cehak A. Trans- and paracellular calcium transport along the small and large intestine in horses.. Comp. Biochem. Physiol. Part A Mol. Integr. Physiol. 2017;204:157–163.
    doi: 10.1016/j.cbpa.2016.11.020pubmed: 27915149google scholar: lookup
  28. Reichert C, Kästner SBR, Hopster K, Rohn K, Rötting AK. Use of micro-lightguide spectrophotometry for evaluation of microcirculation in the small and large intestines of horses without gastrointestinal disease.. Am. J. Vet. Res. 2014;75:990–996.
    doi: 10.2460/ajvr.75.11.990pubmed: 25350089google scholar: lookup