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Equine veterinary journal2020; 52(4); 577-584; doi: 10.1111/evj.13224

Lamellar energy metabolism and perfusion in the euglycaemic hyperinsulinaemic clamp model of equine laminitis.

Abstract: Hyperinsulinaemia is associated with the development of endocrinopathic laminitis; however, the mechanisms remain unclear. Objective: Evaluate the effects of hyperinsulinaemia on lamellar energy metabolism and perfusion during laminitis development. Methods: In vivo experiment. Methods: Eight Standardbred horses were instrumented with a microdialysis probe in the lamellae of a forelimb. A 24 hours baseline period (BASELINE) was followed by 48 hours of a continuous euglycaemic hyperinsulinaemic clamp (EHC) from 24 to 72 hours (CLAMP). Microdialysate was collected every 6 hours and analysed for glucose, lactate and pyruvate concentrations and lactate-to-pyruvate ratio (L:P). Microdialysis urea clearance was used to estimate lamellar tissue perfusion. Archived microdialysis samples from six identically instrumented Standardbred horses served as controls (CON). Variables were compared over time and between EHC and CON horses using a mixed-effects linear regression model. Results: Glucose concentration decreased during the CLAMP period in CON and EHC horses (P  .9). Lactate concentration increased during the CLAMP period in CON and EHC horses (P < .001), however, the rate of increase was significantly higher in EHC horses relative to CON (P = .014). There was a relative increase in pyruvate concentration in EHC horses compared with CON during the CLAMP period (P = .03). L:P increased significantly in CON horses during the CLAMP period (P < .001) but not in EHC (P = .1). Urea clearance did not change in CON (P = .9) or EHC (P = .05) during the CLAMP, but did increase in EHC relative to CON (P = .02). Conclusions: The effects of microdialysis probe implantation on perfusion and metabolism remain unclear. The EHC model may not mimic natural endocrinopathic laminitis. Conclusions: Laminitis developed without evidence of lamellar hypoperfusion or energy stress. Therapies to improve perfusion are unlikely to affect the initial development of endocrinopathic laminitis.
Publication Date: 2020-02-12 PubMed ID: 31845378DOI: 10.1111/evj.13224Google Scholar: Lookup
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  • Journal Article

Summary

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The study carried out an in vivo experiment to examine the impacts of high insulin levels on equine laminitis development through lamellar energy metabolism and perfusion. The research reveals that laminitis develops without evidencing lamellar hypoperfusion or energy stress.

The Experiment

  • The researchers conducted an in-vivo experiment on eight Standardbred horses that were installed with a microdialysis probe in the lamellae of a forelimb.
  • They initiated with a 24 hours baseline period (BASELINE) which was followed by 48 hours of a continuous euglycaemic hyperinsulinaemic clamp (EHC).
  • The microdialysate was collected at intervals of 6 hours and analyzed for its glucose, lactate, and pyruvate concentrations and lactate-to-pyruvate ratio (L:P).
  • The researchers used microdialysis urea clearance to estimate lamellar tissue perfusion.
  • Archived microdialysis samples from six control Standardbred horses were also included for comparison.
  • A mixed-effects linear regression model was used to compare variables over time and between the EHC and control horses.

Findings

  • The glucose concentration was found to decrease during the clamp period in both the control and EHC horses. However, there were no significant differences between the control and EHC horses.
  • The lactate concentration increased during the clamp period in both the control and EHC horses. The rate of increase was significantly higher in the EHC horses as compared to control horses.
  • The EHC horses showed a relative increase in pyruvate concentration when compared to control horses during the clamp period.
  • There was a significant increase in the lactate-to-pyruvate ratio in control horses during the clamp period, but not in the EHC horses.
  • The urea clearance did not change in control horses or EHC horses during the clamp period, although it did increase in EHC horses relative to control horses.

Conclusions

  • The impacts of inserting a microdialysis probe on metabolism and perfusion are yet to be fully understood.
  • The applicability of the EHC model potentially does not entirely reflect natural endocrinopathic laminitis.
  • Laminitis developed without any indication of lamellar hypoperfusion or energy stress. As such, the study suggests that treatment methods aimed at improving perfusion are unlikely to affect the initial development of endocrinopathic laminitis.

Cite This Article

APA
Stokes SM, Bertin FR, Stefanovski D, Belknap JK, Medina-Torres CE, Pollitt CC, van Eps AW. (2020). Lamellar energy metabolism and perfusion in the euglycaemic hyperinsulinaemic clamp model of equine laminitis. Equine Vet J, 52(4), 577-584. https://doi.org/10.1111/evj.13224

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 52
Issue: 4
Pages: 577-584

Researcher Affiliations

Stokes, Simon M
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Qld, Australia.
Bertin, Francois R
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Qld, Australia.
Stefanovski, Darko
  • New Bolton Center, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania.
Belknap, James K
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio.
Medina-Torres, Carlos E
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Qld, Australia.
Pollitt, Christopher C
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Qld, Australia.
van Eps, Andrew W
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Qld, Australia.
  • New Bolton Center, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania.

MeSH Terms

  • Animals
  • Energy Metabolism
  • Foot Diseases / veterinary
  • Glucose Clamp Technique / veterinary
  • Hoof and Claw
  • Horse Diseases
  • Horses
  • Inflammation / veterinary

Grant Funding

  • Grayson Jockey Club Research Foundation

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Citations

This article has been cited 2 times.
  1. Storms N, Medina Torres C, Franck T, Sole Guitart A, de la Rebière G, Serteyn D. Presence of Myeloperoxidase in Lamellar Tissue of Horses Induced by an Euglycemic Hyperinsulinemic Clamp.. Front Vet Sci 2022;9:846835.
    doi: 10.3389/fvets.2022.846835pubmed: 35359667google scholar: lookup
  2. 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