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Equine veterinary journal2019; 51(5); 658-664; doi: 10.1111/evj.13072

Continuous digital hypothermia prevents lamellar failure in the euglycaemic hyperinsulinaemic clamp model of equine laminitis.

Abstract: Continuous digital hypothermia can prevent the development and progression of laminitis associated with sepsis but its effects on laminitis due to hyperinsulinaemia are unknown. Objective: To determine the effects of continuous digital hypothermia on laminitis development in the euglycaemic hyperinsulinaemic clamp model. Methods: Randomised, controlled (within subject), blinded, experiment. Methods: Eight clinically normal Standardbred horses underwent laminitis induction using the euglycaemic hyperinsulinaemic clamp model (EHC). At initiation of the EHC, one forelimb was continuously cooled (ICE), with the other maintained at ambient temperature (AMB). Dorsal lamellar sections (proximal, middle, distal) were harvested 48 h after initiation of the EHC and were analysed using histological scoring (0-3) and histomorphometry. Cellular proliferation was quantified by counting epidermal cell nuclei staining positive with an immunohistochemical proliferation marker (TPX2). Results: Severe elongation and disruption of SEL with dermo-epidermal separation (score of 3) was observed in all AMB feet at one or more section locations, but was not observed in any ICE sections. Overall 92% of the AMB sections received the most severe histological score (grade 3) and 8% were grade 2, whereas ICE sections were classified as either grade 1 (50%) or grade 2 (50%). Relative to AMB feet, ICE sections were 98% less likely to exhibit grades 2 or 3 (OR: 0.02, 95% CI 0.001, 0.365; P<0.01). Histomorphometry measurements of total and nonkeratinised primary epidermal lamellar length were significantly increased (P<0.01) in AMB limbs compared with ICE. TPX2 positive cell counts were significantly increased (P<0.01) in AMB limbs compared with ICE. Conclusions: Continuous digital hypothermia was initiated before recognition of laminitis and therefore the clinical applicability requires further investigation. Conclusions: Continuous digital hypothermia reduced the severity of laminitis in the EHC model and prevented histological lesions compatible with lamellar structural failure.
Publication Date: 2019-02-07 PubMed ID: 30636340DOI: 10.1111/evj.13072Google Scholar: Lookup
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  • Clinical Trial
  • Veterinary
  • Journal Article

Summary

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This research investigates the impact of continuous digital hypothermia on the development of laminitis, a severe hoof disease in horses. Under the guided conditions of a euglycaemic hyperinsulinaemic clamp model, the research shows that continuous digital hypothermia helped reduce the severity of laminitis and prevented lamellar structural failure.

Study Overview and Methodology

  • The study was performed on eight Standardbred horses which were deemed clinically normal. The induction of laminitis in the horses was brought about using the euglycaemic hyperinsulinaemic clamp model (EHC).
  • Hypothermia was applied continuously to one of the forelimbs (ICE) following the initiation of the EHC model, with the contralateral limb maintained at ambient temperature (AMB).
  • The lamellar sections (proximal, middle, distal) of the dorsal area were harvested and studied 48 hours after the EHC induction.
  • The sections were analysed using histological scoring from 0 to 3 and through histomorphometry. They also measured cell proliferation through the counting of epidermal cell nuclei staining positive with an immunohistochemical proliferation marker (TPX2).

Research Findings

  • Intense elongation and disruption in the Stratum Externum Lamellatum (SEL) with separation between the dermis and epidermis (a score of 3) was noted in all AMB limbs at one or more section locations. On the other hand, none of these severe symptoms were observed in any of the ICE sections.
  • A whopping 92% of the AMB sections received the most severe grade (grade 3), with the remaining 8% at grade 2. In stark contrast, the ICE sections scored only grade 1 (50%) or grade 2 (50%).
  • In comparison to the AMB limbs, the ICE sections were 98% less likely to exhibit a grade 2 or 3 score.
  • Metrics such as total and nonkeratinised primary epidermal lamellar length significantly increased in AMB limbs compared to ICE. Similarly, TPX2 positive cell counts were significantly higher in AMB limbs than in ICE.

Conclusion

  • The application of continuous digital hypothermia began before the detection of laminitis, opening further need for research into its clinical applicability.
  • The study nonetheless concludes that continuous digital hypothermia could reduce laminitis severity and forestall compatible histological lesions with lamellar structural failure in the EHC model.

Cite This Article

APA
Stokes SM, Belknap JK, Engiles JB, Stefanovski D, Bertin FR, Medina-Torres CE, Horn R, van Eps AW. (2019). Continuous digital hypothermia prevents lamellar failure in the euglycaemic hyperinsulinaemic clamp model of equine laminitis. Equine Vet J, 51(5), 658-664. https://doi.org/10.1111/evj.13072

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 51
Issue: 5
Pages: 658-664

Researcher Affiliations

Stokes, S M
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, the University of Queensland, Gatton, Queensland, Australia.
Belknap, J K
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, the Ohio State University, Columbus, Ohio, USA.
Engiles, J B
  • New Bolton Center, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.
  • New Bolton Center, Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.
Stefanovski, D
  • New Bolton Center, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.
Bertin, F R
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, the University of Queensland, Gatton, Queensland, Australia.
Medina-Torres, C E
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, the University of Queensland, Gatton, Queensland, Australia.
Horn, R
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, the University of Queensland, Gatton, Queensland, Australia.
van Eps, A 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
  • Cryotherapy / veterinary
  • Foot Diseases / chemically induced
  • Foot Diseases / prevention & control
  • Foot Diseases / veterinary
  • Gene Expression Regulation / drug effects
  • Glucose Clamp Technique / veterinary
  • Hoof and Claw / pathology
  • Horse Diseases / chemically induced
  • Horses
  • Inflammation / chemically induced
  • Inflammation / prevention & control
  • Inflammation / veterinary
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism

Grant Funding

  • Grayson Jockey Club Research Foundation

Citations

This article has been cited 3 times.
  1. Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses.. Vet Sci 2022 Oct 10;9(10).
    doi: 10.3390/vetsci9100556pubmed: 36288169google scholar: lookup
  2. Stokes SM, Stefanovski D, Bertin FR, Medina-Torres CE, Belknap JK, van Eps AW. Plasma amino acid concentrations during experimental hyperinsulinemia in 2 laminitis models.. J Vet Intern Med 2021 May;35(3):1589-1596.
    doi: 10.1111/jvim.16095pubmed: 33704816google scholar: lookup
  3. Stokes SM, Burns TA, Watts MR, Bertin FR, Stefanovski D, Medina-Torres CE, Belknap JK, van Eps AW. Effect of digital hypothermia on lamellar inflammatory signaling in the euglycemic hyperinsulinemic clamp laminitis model.. J Vet Intern Med 2020 Jul;34(4):1606-1613.
    doi: 10.1111/jvim.15835pubmed: 32583504google scholar: lookup