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Home / Equine Research Bank / J Vet Intern Med / Effect of digital hypothermia on lamellar inflammatory signa...
Journal of veterinary internal medicine2020; 34(4); 1606-1613; doi: 10.1111/jvim.15835

Effect of digital hypothermia on lamellar inflammatory signaling in the euglycemic hyperinsulinemic clamp laminitis model.

Abstract: Continuous digital hypothermia (CDH) prevents lamellar failure in the euglycemic hyperinsulinemic clamp (EHC) model of laminitis, but the protective mechanisms are unclear. Objective: To determine if CDH inhibits lamellar inflammatory signaling in the EHC model of laminitis. Methods: Eight Standardbred horses. Methods: Prospective experimental study. Horses underwent an EHC, with 1 forelimb treated with CDH and the other kept at ambient temperature (AMB). Horses were euthanized 48 hours after initiation of the EHC and lamellar tissue was analyzed via polymerase chain reaction (pro-inflammatory cytokine and chemokine genes-CXCL1, CXCL6, CXCL8, IL-6, MCP-1, MCP-2, IL-1β, IL-11, cyclooxygenase 1 and 2, tumour necrosis factor-alpha [TNF-α], E-selectin, and intercellular adhesion molecule-1 [ICAM-1]) and immunoblotting (phosphorylated and total signal transducer and activator of transcription 1 [STAT1] and STAT3). Results: Compared to AMB, lamellar messenger ribonucleic acid (mRNA) concentrations of CXCL6 (P =.02), CXCL8 (P = .008), IL-6 (P = .008), IL-1β (P = .008), IL-11 (P = .008), and cyclooxygenase-2 (P = .008) were decreased in CDH. Cyclooxygenase-1 (P = .008) was increased in CDH, while CXCL1 (P = .15), MCP-1 (P = .05), MCP-2 (P = .46), TNF-α (P = .05), E-selectin (P = .15), and ICAM-1 (P = .15) mRNA were not significantly different. Compared to AMB, lamellar concentration of total STAT3 protein was decreased in CDH (P < .001), but there was no change in phosphorylated STAT3 (P-STAT3 [S727] P = .19; P-STAT3 [Y705] P = .05). There was no change in lamellar concentrations of total STAT1 (P = .75) or phosphorylated STAT1 (P-STAT1 [S727], P = .25; P-STAT1 [Y701], P = .64). Conclusions: These data add further support for the use of CDH as a first aid treatment for severe acute laminitis associated with hyperinsulinemia in horses.
© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
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Publication Date: 2020-06-25 PubMed ID: 32583504PubMed Central: PMC7379000DOI: 10.1111/jvim.15835Google Scholar: Lookup
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  • Journal Article

Summary

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This research investigates the role of continuous digital hypothermia (CDH) in reducing the inflammatory signaling associated with laminitis, a painful inflammation common in the feet of horses, using the euglycemic hyperinsulinemic clamp (EHC) model. The findings suggest that CDH may be effective as an early treatment approach for laminitis linked to hyperinsulinemia in horses.

Methods

  • The study involved eight Standardbred horses.
  • Each horse was subjected to an experimental procedure known as the euglycemic hyperinsulinemic clamp (EHC). This method involves controlling the blood glucose and insulin levels of the subject.
  • During the EHC procedure, one of the horse’s forelimbs was treated with continuous digital hypothermia (CDH) while the other remained at ambient temperature.
  • 48 hours after the EHC procedure was initiated, the horses were euthanized and the lamellar tissue, a type of tissue found in horses’ hooves, was collected and examined.
  • The researchers performed a polymerase chain reaction to measure any changes in genes related to inflammation (specifically CXCL1, CXCL6, CXCL8, IL-6, MCP-1, MCP-2, IL-1β, IL-11, cyclooxygenase 1 and 2, tumour necrosis factor-alpha [TNF-α], E-selectin, and ICAM-1).
  • Immunoblotting was also used to study the levels of signal transducer and activator of transcription 1 (STAT1) and STAT3 in the collected tissues.

Findings

  • The study found that levels of some pro-inflammatory signals were decreased in the forelimb treated with CDH compared to the one kept at ambient temperature.
  • Specifically, the concentrations of genes CXCL6, CXCL8, IL-6, IL-1β, IL-11, and cyclooxygenase-2 were decreased in the CDH-treated limb.
  • Cyclooxygenase-1 was increased in the CDH-treated limb.
  • There were no significant differences in mRNA concentrations of CXCL1, MCP-1, MCP-2, TNF-α, E-selectin, and ICAM-1.
  • Total STAT3 protein concentration was found to be lower in the lamellar tissue from CDH-treated limbs.
  • There were no observed changes in the concentration of total STAT1 or phosphorylated STAT1 in lamellar tissues.

Conclusions

  • The data gathered in this study supports the use of continuous digital hypothermia as a first aid treatment for severe acute laminitis associated with hyperinsulinemia in horses.
  • This is because CDH was found to reduce some inflammatory signals in the hoof tissue, potentially alleviating the painful inflammation associated with laminitis.

Cite This Article

APA
Stokes SM, Burns TA, Watts MR, Bertin FR, Stefanovski D, Medina-Torres CE, Belknap JK, van Eps AW. (2020). Effect of digital hypothermia on lamellar inflammatory signaling in the euglycemic hyperinsulinemic clamp laminitis model. J Vet Intern Med, 34(4), 1606-1613. https://doi.org/10.1111/jvim.15835

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 34
Issue: 4
Pages: 1606-1613

Researcher Affiliations

Stokes, Simon M
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
Burns, Teresa A
  • Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
Watts, Mauria R
  • Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
Bertin, François-René
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
Stefanovski, Darko
  • New Bolton Center, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.
Medina-Torres, Carlos E
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
Belknap, James K
  • Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
van Eps, Andrew W
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
  • New Bolton Center, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.

MeSH Terms

  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Foot Diseases / chemically induced
  • Foot Diseases / physiopathology
  • Foot Diseases / veterinary
  • Gene Expression Regulation
  • Glucose Clamp Technique / veterinary
  • Hoof and Claw / pathology
  • Horse Diseases / chemically induced
  • Horse Diseases / physiopathology
  • Horses
  • Hyperinsulinism / veterinary
  • Hypothermia, Induced / veterinary
  • Inflammation / chemically induced
  • Inflammation / physiopathology
  • Inflammation / veterinary
  • Male
  • Prospective Studies
  • Signal Transduction

Grant Funding

  • Grayson-Jockey Club Research Foundation

Conflict of Interest Statement

Authors declare no conflict of interest.

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