Adaptive mechanisms in no flow vs. low flow ischemia in equine jejunum epithelium: Different paths to the same destination

Dengler, Franziska; Sternberg, Felix; Grages, Marei; Kästner, Sabine; Verhaar, Nicole

doi:10.3389/fvets.2022.947482

Cited by 4 publications

(2 citation statements)

References 69 publications

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“…in the histology samples during reperfusion may be the result of increased stabilization instead of upregulation, although no significant upregulation of the target genes GLUT1, EGLN1, and 3 was found. A comparable pattern was seen in another study investigating IRI in horses, with only partial and delayed upregulation of HIF-targets (49). On the other hand, the analysis of the complete mucosa instead of only the enterocytes could have caused smaller differences to go undetected.…”

Section: Figuresupporting

confidence: 75%

Hypoxia signaling in the equine small intestine: Expression and distribution of hypoxia inducible factors during experimental ischemia

Verhaar

Buhr²,

Köckritz-Blickwede³

et al. 2023

Front. Vet. Sci.

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IntroductionHypoxia inducible factors (HIF) are widely researched in human medicine for their role in different disease processes. The aim of this study was to investigate the expression and distribution of HIF in experimental small intestinal ischemia in the horse.MethodsIn 14 horses under general anesthesia, segmental jejunal ischemia with 90% reduction in blood flow was induced. The horses were randomly divided into two groups of seven horses, one subjected to ischemic postconditioning (IPoC) by delayed reperfusion, and a control group (group C) undergoing undelayed reperfusion. Intestinal samples were taken pre-ischemia, after ischemia and after reperfusion. Following immunohistochemical staining for HIF1α and -2α, the immunoreactivity pattern in the small intestine was evaluated by light microscopy, and the mucosal enterocyte and muscularis staining were semi-quantitatively scored. Additionally, mucosal HIF1α protein levels were determined by an Enzyme Linked Immunosorbent Assay (ELISA), and mRNA levels of HIF1α and its target genes by a two-step real-time Reverse Transcriptase Polymerase Chain Reaction. Statistical comparison was performed between the groups and time points using parametric and non-parametric tests (p < 0.05).ResultsAll cell types exhibited cytoplasmic and nuclear immunoreactivity for HIF1α. After reperfusion, the cytoplasmic staining of the crypt and villus enterocytes as well as the villus nuclear staining significantly increased, whereas the perinuclear granules in the crypts decreased. The protein levels showed a significant decrease in group C at reperfusion, with lower HIF1α levels in group C compared to group IPoC during ischemia and reperfusion. No other group differences could be detected. In the HIF2α stained slides, mild to moderate cytoplasmic staining yet no nuclear immunoreactivity of the enterocytes was observed, and no significant changes over time were noted.Discussionthe changes in HIF1α immunoreactivity pattern and expression over time suggest that this transcription factor plays a role in the intestinal response to ischemia in horses. However, the current study could not identify an effect of IPoC on HIF distribution or expression.

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Section: Figuresupporting

confidence: 75%

Hypoxia signaling in the equine small intestine: Expression and distribution of hypoxia inducible factors during experimental ischemia

Verhaar

Buhr²,

Köckritz-Blickwede³

et al. 2023

Front. Vet. Sci.

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“…Biopsies were stored in RNAlater® (Qiagen, Hilden, Germany) at −80°C until RNA isolation. Total RNA was isolated from the tissue, and cDNA was prepared as described previously ( 14 ). Briefly, total RNA was extracted with the ReliaPrep™ RNA Miniprep System (Promega GmbH, Mannheim, Germany) according to the manufacturer’s protocol, including treatment with DNase.…”

Section: Methodsmentioning

confidence: 99%

Dysregulation of intestinal epithelial electrolyte transport in canine chronic inflammatory enteropathy and the role of the renin-angiotensin-aldosterone-system

Dengler,

Domenig,

Kather

et al. 2023

Front. Vet. Sci.

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Chronic diarrhea is a hallmark sign of canine chronic inflammatory enteropathy (CIE), leading to fluid and electrolyte losses. Electrolyte homeostasis is regulated by the renin-angiotensin-aldosterone-system (RAAS), which might be involved in (counter-)regulating electrolyte losses in canine CIE. Whether and which electrolyte transporters are affected or if RAAS is activated in canine CIE is unknown. Thus, intestinal electrolyte transporters and components of the RAAS were investigated in dogs with CIE. Serum RAAS fingerprint analysis by mass spectrometry was performed in 5 CIE dogs and 5 healthy controls, and mRNA levels of intestinal electrolyte transporters and local RAAS pathway components were quantified by RT-qPCR in tissue biopsies from the ileum (7 CIE, 10 controls) and colon (6 CIE, 12 controls). Concentrations of RAAS components and mRNA expression of electrolyte transporters were compared between both groups of dogs and were tested for associations among each other. In dogs with CIE, associations with clinical variables were also tested. Components of traditional and alternative RAAS pathways were higher in dogs with CIE than in healthy controls, with statistical significance for Ang I, Ang II, and Ang 1–7 (all p < 0.05). Expression of ileal, but not colonic electrolyte transporters, such as Na+/K+-ATPase, Na+/H+-exchanger 3, Cl− channel 2, down-regulated in adenoma, and Na+-glucose-cotransporter (all p < 0.05) was increased in CIE. Our results suggest that the dys- or counter-regulation of intestinal electrolyte transporters in canine CIE might be associated with a local influence of RAAS. Activating colonic absorptive reserve capacities may be a promising therapeutic target in canine CIE.

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Flowmetry and spectrophotometry for the assessment of intestinal viability in horses with naturally occurring strangulating small intestinal lesions

Verhaar,

Grages,

Bienert‐Zeit

et al. 2024

Equine Veterinary Journal

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BackgroundAncillary diagnostic methods to enhance the accuracy of viability assessment have not been established for use in clinical practice.ObjectivesTo assess intestinal microperfusion measured by Laser Doppler Flowmetry and Spectrophotometry (LDFS) in naturally occurring small intestinal strangulations of different origins and to compare this between viable and non‐viable segments.Study designProspective clinical trial.MethodsForty horses undergoing colic surgery for naturally occurring small intestinal strangulations were included. Tissue oxygen saturation (tSO2), haemoglobin (tHB) and blood flow (tBF) were determined by LDFS before and after release of the strangulation. Intestinal biopsies were taken in cases that underwent intestinal resection or intraoperative euthanasia and assessed using a semi‐quantitative mucosal injury score (MIS). The LDFS measurements were compared between the different categories of strangulation causes and histopathological injury using parametric and non‐parametric tests (p < 0.05).ResultsStrangulations by pedunculated lipomas had lower tBF (13.9 ± 18 arbitrary units [AU]) than epiploic foramen entrapments (65.2 ± 61 AU; CI −1.697 to −0.2498; p = 0.005). Segments with MIS > 5 showed lower tBF during strangulation than segments with MIS < 4 (mean difference 61.1 AU; CI −1.119 to −0.07361; p = 0.03). This did not differ significantly following release of strangulation. Furthermore, there was a positive correlation between the inflammatory cell count and tBF during strangulation (r 0.34; CI 0.01 to 0.60; p = 0.04). The tSO2 and tHB did not differ between the different categories of lesions or injury.Main limitationsNo biopsies could be taken from the intestinal segments that did not undergo resection. The duration of strangulation could not reliably be ascertained.ConclusionsBlood flow measurements in naturally occurring strangulating lesions show a varying degree of ischaemia in different causes of strangulation. Intestinal blood flow measurements prior to release of the strangulation could potentially contribute to the identification of mucosal injury, yet a high individual variability and other contributing factors need to be considered.

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Adaptive mechanisms in no flow vs. low flow ischemia in equine jejunum epithelium: Different paths to the same destination

Cited by 4 publications

References 69 publications

Hypoxia signaling in the equine small intestine: Expression and distribution of hypoxia inducible factors during experimental ischemia

Hypoxia signaling in the equine small intestine: Expression and distribution of hypoxia inducible factors during experimental ischemia

Dysregulation of intestinal epithelial electrolyte transport in canine chronic inflammatory enteropathy and the role of the renin-angiotensin-aldosterone-system

Flowmetry and spectrophotometry for the assessment of intestinal viability in horses with naturally occurring strangulating small intestinal lesions

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