Ischaemic postconditioning reduces apoptosis in experimental jejunal ischaemia in horses.
Abstract: Ischaemic postconditioning (IPoC) refers to brief periods of reocclusion of blood supply following an ischaemic event. This has been shown to ameliorate ischaemia reperfusion injury in different tissues, and it may represent a feasible therapeutic strategy for ischaemia reperfusion injury following strangulating small intestinal lesions in horses. The objective of this study was to assess the degree cell death, inflammation, oxidative stress, and heat shock response in an equine experimental jejunal ischaemia model with and without IPoC. Methods: In this randomized, controlled, experimental in vivo study, 14 horses were evenly assigned to a control group and a group subjected to IPoC. Under general anaesthesia, segmental ischaemia with arterial and venous occlusion was induced in 1.5 m jejunum. Following ischaemia, the mesenteric vessels were repeatedly re-occluded in group IPoC only. Full thickness intestinal samples and blood samples were taken at the end of the pre-ischaemia period, after ischaemia, and after 120 min of reperfusion. Immunohistochemical staining or enzymatic assays were performed to determine the selected variables. Results: The mucosal cleaved-caspase-3 and TUNEL cell counts were significantly increased after reperfusion in the control group only. The cleaved-caspase-3 cell count was significantly lower in group IPoC after reperfusion compared to the control group. After reperfusion, the tissue myeloperoxidase activity and the calprotectin positive cell counts in the mucosa were increased in both groups, and only group IPoC showed a significant increase in the serosa. Tissue malondialdehyde and superoxide dismutase as well as blood lactate levels showed significant progression during ischaemia or reperfusion. The nuclear immunoreactivity of Heat shock protein-70 increased significantly during reperfusion. None of these variables differed between the groups. The neuronal cell counts in the myenteric plexus ganglia were not affected by the ischaemia model. Conclusions: A reduced apoptotic cell count was found in the group subjected to IPoC. None of the other tested variables were significantly affected by IPoC. Therefore, the clinical relevance and possible protective mechanism of IPoC in equine intestinal ischaemia remains unclear. Further research on the mechanism of action and its effect in clinical cases of strangulating colic is needed.
Publication Date: 2021-04-26 PubMed ID: 33902575PubMed Central: PMC8077964DOI: 10.1186/s12917-021-02877-yGoogle Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Veterinary
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 explores how Ischaemic postconditioning (IPoC), a process involving short periods of re-blocking blood supply after an ischaemic (restricted blood flow) event, can reduce cell death in horse intestine exposed to ischaemia reperfusion injury. Using a group of 14 horses, the researchers performed controlled tests and determined that IPoC can potentially limit damage in such conditions, though further analysis is needed for confirmation.
Research Methodology
- In this experimental study, researchers divided 14 horses into two groups – a control group and the group subjected to Ischaemic postconditioning (IPoC).
- Under general anaesthesia, a segmental ischaemia was induced in the horses’ small intestine, more specifically 1.5-meter jejunum, by blocking the arterial and venous blood supply.
- After the ischaemia event, the blood vessels of the small intestine were repeatedly re-blocked in the group that was subjected to IPoC.
- The teams took samples of the full thickness of the intestine and blood at different stages – before ischaemia, after ischaemia, and following 120 minutes of reperfusion for examination and biochemical analysis.
Findings of the Study
- The study found that cell death (as determined by cell counts of cleaved-caspase-3 and TUNEL) significantly increased after reperfusion in the control group, while the IPoC group showed significantly lower cleaved-caspase-3 cell counts after reperfusion.
- Both groups showed increased tissue myeloperoxidase activity and calprotectin positive cell counts in the intestine’s mucosa after reperfusion. However, a significant increase in the serosa was observed only in the IPoC group.
- The levels of tissue malondialdehyde, superoxide dismutase, and blood lactate, which are markers for oxidative stress and blood acidity respectively, were found to increase notably after ischaemia or reperfusion.
- Heat shock protein-70, responsible for cellular protection in stress conditions, also showed significant increases during the reperfusion phase. However, these increases did not differ between groups.
- The cell counts of the myenteric plexus ganglia were not affected by the ischaemia model deployed in the study.
Conclusion and Further Work
- The significant findings of the study was the observed reduction in apoptosis (programmed cell death) in the IPoC group.
- However, none of the other tested variables (inflammation, oxidative stress, heat shock response) showed significant changes between the groups.
- As a result, the researchers concluded that while IPoC appears to have some protective effect by reducing apoptosis, the exact mechanism and clinical significance in equine intestinal ischaemia remains unclear.
- The paper suggests further research needs to be conducted to understand the mechanism of action and the potential application of IPoC in treating clinical cases of strangulating colic in horses.
Cite This Article
APA
Verhaar N, de Buhr N, von Köckritz-Blickwede M, Hewicker-Trautwein M, Pfarrer C, Mazzuoli-Weber G, Schulte H, Kästner S.
(2021).
Ischaemic postconditioning reduces apoptosis in experimental jejunal ischaemia in horses.
BMC Vet Res, 17(1), 175.
https://doi.org/10.1186/s12917-021-02877-y Publication
Researcher Affiliations
- Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany. nicole.verhaar@tiho-hannover.de.
- Department of Biochemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
- Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Hannover, Germany.
- Department of Biochemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
- Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Hannover, Germany.
- Institute of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
- Institute for Anatomy, University of Veterinary Medicine Hannover, Hannover, Germany.
- Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hannover, Germany.
- Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
- Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
- Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover, Germany.
MeSH Terms
- Animals
- Apoptosis
- HSP70 Heat-Shock Proteins / metabolism
- Horses
- Intestinal Mucosa / metabolism
- Ischemic Postconditioning / methods
- Ischemic Postconditioning / veterinary
- Jejunum / blood supply
- Jejunum / pathology
- Lactic Acid / blood
- Malondialdehyde / metabolism
- Reperfusion Injury / therapy
- Reperfusion Injury / veterinary
- Superoxide Dismutase / metabolism
Conflict of Interest Statement
The authors declare that they have no competing interests.
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Citations
This article has been cited 3 times.- 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.
- 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.
- 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).
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