Evidence for vascular and enzymatic events in the pathophysiology of acute laminitis: which pathway is responsible for initiation of this process in horses?
Abstract: To date, there is a substantial amount of data to support the hypotheses that vascular and enzymatic changes are ongoing in experimental laminitis. Furthermore, there is substantial in vitro evidence that the enzymatic changes weaken the dermo-epidermal attachments leading to mechanical failure of the hoof-bone interface of the equine digit. However, investigators of both the vascular and enzymatic theories have, to date, been unable to substantiate the effects of these pathophysiological changes in vivo on laminar tissues of horses afflicted with experimentally induced or naturally acquired laminitis. In addition, the effects of laminitis-inducing treatment have not been prevented or reversed by treatment with an MMP inhibitor or a vasoactive antagonist. It is possible that there is simultaneous activation of the vascular and enzymatic pathways and/or other inflammatory processes. Moreover, the third theory involving mechanical factors cannot be discounted simply because strong evidence for vascular and enzymatic changes exists. It is common for horses with severe musculoskeletal disease affecting weightbearing on a limb to develop laminitis in the contralateral limb. It remains to be determined what factors are responsible for initiation of laminitis in these individuals. Evidence has not been presented that precludes the possibility of coincident occurrence of vascular and enzymatic changes. In fact, many of the inflammatory mediators (e.g. interleukin-1beta) found in laminitic tissues can concurrently stimulate synthesis of vasoactive substances and activate MMPs. Because enzymatic action on proteins is largely dependent on the concentrations of proteins and enzyme, the enzymatic theory is not dependent upon increased delivery of enzymes via increased capillary flow. Likewise, because vascular changes can alter tissue function via increased capillary flow and oedema formation, the vascular theory is not dependent upon decreased capillary flow. It is true that naturally acquired laminitis is widely variable in severity and predisposing diseases. Therefore, most probably there are multiple mechanisms involved in the initiation and propagation of the pathophysiologic cascade(s) and, therefore, successful intervention will necessitate multiple treatment modalities.
Publication Date: 2004-05-19 PubMed ID: 15147125DOI: 10.2746/0425164044877116Google Scholar: Lookup
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This research paper explores the possible causes behind acute laminitis in horses, suggesting that vascular and enzymatic changes could play a significant part. However, it acknowledges the difficulty in proving these theories with in vivo testing and highlights the potential of other factors, such as mechanical issues or concurrent inflammatory processes.
Vascular and Enzymatic Changes in Laminitis
- The paper discusses evidence suggesting the existence of both vascular and enzymatic changes in cases of experimental laminitis (inflammation of the soft tissue structures within the hoof of a horse).
- These changes seem to weaken the attachment between the skin and underlying tissue (dermo-epidermal attachment), leading to a failure in the connection between the horse’s hoof and bone.
- However, it’s difficult to firmly establish the effects of these vascular and enzymatic changes on the laminar tissues of horses suffering from laminitis in a real-life scenario (in vivo).
Lack of Clarity on Cause & Effect
- The paper notes a lack of success in preventing or reversing the effects of laminitis-inducing treatment through the use of Matrix Metalloproteinase (MMP) inhibitors or vasoactive antagonists (drugs that oppose or inhibit the action of vasoactive substances, which affect the constriction or dilation of blood vessels).
- While vascular and enzymatic changes might be part of the cause, simultaneous activation of these (and potentially other, inflammatory) processes could also be a factor.
- Alternatively, mechanical factors may also play a role, as it’s common for horses with severe musculoskeletal diseases to develop laminitis in the opposite limb.
Complexities of Laminitis Initiation
- The paper admits the existing evidence doesn’t exclude the possibility of simultaneous vascular and enzymatic changes. Moreover, certain inflammatory substances found in laminitic tissues such as Interleukin 1-beta can stimulate the synthesis of both vasoactive substances and MMP.
- It’s important to note that the concentration of proteins and enzymes can influence the impact of enzymatic changes — meaning these changes might occur regardless of the delivery of enzymes through increased blood flow.
- In the same vein, vascular changes may alter tissue function through enhanced blood flow and oedema formation, regardless of reduced capillary flow.
- The authors highlight the varied severity and predisposing conditions of naturally acquired laminitis, suggesting multiple mechanisms might be involved in triggering and perpetuating the associated pathological processes.
Implications for Treatment
- Given the complexity and potential variability of laminitis initiation, successful intervention will likely require multiple treatment strategies.
Cite This Article
APA
Moore RM, Eades SC, Stokes AM.
(2004).
Evidence for vascular and enzymatic events in the pathophysiology of acute laminitis: which pathway is responsible for initiation of this process in horses?
Equine Vet J, 36(3), 204-209.
https://doi.org/10.2746/0425164044877116 Publication
Researcher Affiliations
- Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
MeSH Terms
- Acute Disease
- Animals
- Foot Diseases / enzymology
- Foot Diseases / etiology
- Foot Diseases / physiopathology
- Foot Diseases / veterinary
- Hemodynamics
- Hoof and Claw / blood supply
- Hoof and Claw / enzymology
- Hoof and Claw / physiology
- Horse Diseases / enzymology
- Horse Diseases / etiology
- Horse Diseases / physiopathology
- Horses
- Inflammation / enzymology
- Inflammation / etiology
- Inflammation / physiopathology
- Inflammation / veterinary
Citations
This article has been cited 4 times.- Blaettler C, Kaessmeyer S, Grabherr S, Koch C, Schweizer D, Van der Vekens E. Post-mortem Computed Tomographic Angiography in Equine Distal Forelimbs: A Feasibility Study.. Front Vet Sci 2022;9:868390.
- Al-Agele R, Paul E, Taylor S, Watson C, Sturrock C, Drakopoulos M, Atwood RC, Rutland CS, Menzies-Gow N, Knowles E, Elliott J, Harris P, Rauch C. Physics of animal health: on the mechano-biology of hoof growth and form.. J R Soc Interface 2019 Jun 28;16(155):20190214.
- Martin EM, Messenger KM, Sheats MK, Jones SL. Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes.. Front Vet Sci 2017;4:160.
- Leise BS, Watts MR, Roy S, Yilmaz AS, Alder H, Belknap JK. Use of laser capture microdissection for the assessment of equine lamellar basal epithelial cell signalling in the early stages of laminitis.. Equine Vet J 2015 Jul;47(4):478-88.
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