Effect of Continuous Digital Hypothermia on Lamellar Inflammatory Signaling When Applied at a Clinically-Relevant Timepoint in the Oligofructose Laminitis Model.
Abstract: Although continuous digital hypothermia (CDH) protects lamellae from injury in the oligofructose (OF) model of sepsis-related laminitis (SRL), conflicting results exist from these studies regarding effects of CDH on lamellar inflammatory events. Objective: To determine the effect of CDH on lamellar inflammatory events in normal and OF-treated horses when instituted at a clinically relevant time point (onset of clinical signs of sepsis in this model). Methods: Standardbred geldings (n = 15) aged 3-11 years were used. Methods: In a randomized, controlled discovery study, animals were administered either OF (OF group, n = 8) or water (CON group, n = 8) by nasogastric tube and CDH was initiated in one forelimb (ICE) 12 hours later. Lamellar tissue samples were collected 24 hours after initiation of CDH (ICE and ambient [AMB] forelimbs). Lamellar mRNA concentrations of inflammatory mediators and lamellar leukocyte numbers were assessed using qPCR and immunohistochemistry, respectively; values from four sample groups (CON AMB, OF AMB, CON ICE, and OF ICE) were analyzed using mixed model linear regression. Results: Although lamellar mRNA concentrations of multiple inflammatory mediators (IL-1β, IL-6, CXCL1, MCP2, COX-2) were increased after OF administration (OF AMB group versus CON AMB; P < 0.05), only 2 inflammatory mediators (IL-6 and COX-2) and lamellar leukocyte numbers were decreased with CDH (OF ICE versus OF AMB; P < 0.05). Conclusions: Continuous digital hypothermia initiated at a time point similar to that commonly used clinically (clinical onset of sepsis) resulted in a more focused inhibition of inflammatory signaling.
Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Publication Date: 2017-12-27 PubMed ID: 29282770PubMed Central: PMC5787192DOI: 10.1111/jvim.15027Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
Summary
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The research focuses on the effect of continuous digital hypothermia (CDH) on inflammatory signals within the hoof structure of horses during the onset of sepsis-related laminitis, a common horse disease. The study found that the application of CDH at clinically relevant times reduced select inflammation markers and leukocyte numbers.
Methods
- 15 Standardbred geldings aged 3-11 years were used in the study, which was randomized and controlled.
- The horses were administered oligofructose (OF) to induce sepsis-related laminitis or water as a control via a nasogastric tube.
- 12 hours later, CDH was applied to one forelimb, labelling it as the “ICE” group. The other forelimb, exposed to ambient conditions, was the “AMB” group.
- 24 hours after the initiation of CDH, samples of lamellar tissue (the sensitive tissue inside the hoof) were collected from both the ICE and AMB groups.
- The samples were assessed for mRNA concentrations of inflammatory mediators and lamellar leukocyte numbers using a technique known as quantitative polymerase chain reaction (qPCR) and immunohistochemistry, respectively.
Results
- The lamellar mRNA concentrations of several inflammatory mediators were found to be increased in the OF AMB group, indicating the successful induction of inflammation typically seen in sepsis-related laminitis.
- However, applying CDH (in the OF ICE group) resulted in reduced levels of two specific inflammatory mediators, IL-6 and COX-2, as well as a decrease in lamellar leukocyte numbers, demonstrating the anti-inflammatory effects of CDH.
Conclusions
- The study concluded that the application of CDH at a clinically relevant time (onset of clinical signs of sepsis) resulted in a more focused inhibition of inflammatory signaling.
- This research supports the use of CDH as a strategy to control inflammation in the laminitis model, but also suggests that its effects are somewhat specific, as not all inflammatory markers showed significant reduction.
Cite This Article
APA
Dern K, van Eps A, Wittum T, Watts M, Pollitt C, Belknap J.
(2017).
Effect of Continuous Digital Hypothermia on Lamellar Inflammatory Signaling When Applied at a Clinically-Relevant Timepoint in the Oligofructose Laminitis Model.
J Vet Intern Med, 32(1), 450-458.
https://doi.org/10.1111/jvim.15027 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, Ohio State University, Columbus, OH, USA.
- Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Qld, Australia.
- Department of Veterinary Preventive Medicine, Ohio State University, Columbus, OH, USA.
- Department of Veterinary Clinical Sciences, Ohio State University, Columbus, OH, USA.
- Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Qld, Australia.
- Department of Veterinary Clinical Sciences, Ohio State University, Columbus, OH, USA.
MeSH Terms
- Animals
- Cytokines / metabolism
- Foot Diseases / pathology
- Foot Diseases / therapy
- Foot Diseases / veterinary
- Hoof and Claw / pathology
- Horse Diseases / pathology
- Horse Diseases / therapy
- Horses
- Hypothermia, Induced / veterinary
- Inflammation / therapy
- Inflammation / veterinary
- Leukocytes / pathology
- Male
- Oligosaccharides / administration & dosage
- Oligosaccharides / toxicity
- RNA, Messenger
- Signal Transduction
Conflict of Interest Statement
Authors declare no conflict of interest.
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