Early laminar events involving endothelial activation in horses with black walnut– induced laminitis

Loftus, John P.; Black, Samuel J.; Pettigrew, A.; Abrahamsen, Eric J.; Belknap, James K.

doi:10.2460/ajvr.68.11.1205

Cited by 85 publications

(116 citation statements)

References 28 publications

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“…In study subjects in which laminitis was induced using various models of SRL, marked increases in a wide range of proinflammatory mediators were detected when compared to nonseptic control horses 4, 5, 6, 7, 8. Similar to the reports from the use of moderate regional hypothermia (approximately 30°C) in human patients to limit damage to vital organs in cases of inflammatory injury, continuous marked digital hypothermia (5–10°C) limited the structural failure of the lamellae both in horses with clinical sepsis and in experimentally induced laminitis 7, 9, 10, 11, 12.…”

mentioning

confidence: 99%

Effect of Delayed Digital Hypothermia on Lamellar Inflammatory Signaling in the Oligofructose Laminitis Model

Dern

Watts

Werle

et al. 2017

Veterinary Internal Medicne

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BackgroundIn the oligofructose (OF) model of sepsis‐related laminitis (SRL), digital hypothermia (“cryotherapy”) initiated before the onset of clinical signs is reported not only to limit lamellar injury, but also to cause marked inhibition of lamellar inflammatory signaling.Hypothesis/ObjectivesBecause hypothermia also has been reported to be protective when not initiated until the onset of lameness in the OF model of SRL, we hypothesized that the lamellar protection conferred by hypothermia is caused by local lamellar inhibition of inflammatory signaling as described when hypothermia was initiated earlier in the disease process.AnimalsEight Standardbred geldings aged 3–11 years with no lameness and no abnormalities of the feet detectable by gross or radiographic examination.MethodsUsing the OF model of SRL, lamellar mRNA concentrations of proinflammatory cytokines, chemokines, and endothelial adhesion proteins were compared between samples from treated limbs (CRYO, submerged in ice water for 36 hour starting at the onset of lameness), untreated limbs (NON‐CRYO, opposite limb from CRYO limbs maintained at ambient temperature), and untreated limbs from normal horses in which laminitis was not induced (CON).ResultsAlthough OF administration resulted in increases in lamellar mRNA concentrations of several inflammatory mediators in NON‐CRYO limbs (vs CON), digital hypothermia had no significant effect on these increases.Conclusions and Clinical ImportanceThe lack of inflammatory inhibition in lamellar tissue samples in our study indicates that the protective effects of digital hypothermia instituted at the onset of clinical signs of laminitis do not arise from inhibition of inflammatory pathways.

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mentioning

confidence: 99%

Effect of Delayed Digital Hypothermia on Lamellar Inflammatory Signaling in the Oligofructose Laminitis Model

Dern

Watts

Werle

et al. 2017

Veterinary Internal Medicne

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“…Experimental results demonstrate the absence of xanthine oxidase, an enzyme released during tissue ischemia (LOFTUS et al, 2007), challenging vasoconstriction as the primary event in the development of laminitis. There are studies demonstrating that sub-laminar vasodilation occurs early in the development of the disease, which is associated to the temperature increase and blood flow in laminar tissue (POLLITT& DAVIES, 1998) proven by scintigraph (TROUT et al, 1990), suggesting that increase of irrigation in laminar tissue might contribute to the failure of interdigitations.…”

Section: Ischemic Mechanismsmentioning

confidence: 99%

“…The development phase of laminitis presents various inflammatory events such as elevated acute phase protein concentrations (FAGLIARI et al, 1998), inflammatory cytokines (LOFTUS et al, 2007), reactive oxygen species (HUURLEY et al, 2006) as well as leukocyte infiltration into tissue (HURLEY et al, 2006;FALEIROS et al, 2009a, LASKOSKI et al, 2013. Systemic inflammatory activation may be from infectious origin such as exposure to pathogen-associated molecular patterns (PAMPs), or even, due to extensive tissue damage associated with endogenous release of the damage associated molecular patterns (DAMPs).…”

Section: Inflammatory Mechanismsmentioning

confidence: 99%

An update on equine laminitis

et al. 2016

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“…Despite recent evidence indicating leukocyte involvement in laminitis development (Black et al 2006, Hurley et al 2006, Loftus et al 2007, Stewart et al 2009, Faleiros et al 2009b, Faleiros et al 2011a, and the therapeutic potential of DF1681B for neutrophil migration in rodents, this drug has not yet been studied in horses.…”

Section: Introductionmentioning

confidence: 99%

“…Dermal-epidermal junction collapse is common in laminitis of numerous etiologies, but the initial event triggering the structural failure remains poorly understood (Katz & Bailey 2012). Multiple studies propose resident leukocyte activation in the lamella and leukocytic infiltration from the bloodstream, associated with systemic inflammatory response syndrome (SIRS), as probable mechanisms that initiate structural failure (Black et al 2006, Hurley et al 2006, Loftus et al 2007, Stewart et al 2009, Faleiros et al 2009b, Faleiros et al 2011a. Increased pro-inflammatory cytokine expression (mainly IL-1β and IL-6), as well as CXC and CCR chemokines, during the developmental stage, indicates that these molecules may play an important role in leukocyte migration in the early events of laminitis , Faleiros et al 2009a, Leise et al 2011, Faleiros et al 2011b, Visser et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Histologic and inflammatory lamellar changes in horses with oligofructose-induced laminitis treated with a CXCR1/2 antagonist

et al. 2016

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RESUMO.-[Alterações histológicas e inflamatórias no tecido laminar de equinos submetidos ao modelo de laminite por oligofrutose e tratados com um antagonista para CXCR1/2.] A expressão de quimiocinas e a infiltração de leucócitos no tecido laminar são característicos de laminite aguda de equinos. O presente estudo avaliou o efeito terapêutico da administração intravenosa de DF1681B , um antagonista seletivo para CXCR1 e CXCR2 (receptores de quimiocinas), em um modelo de laminite equina por oligofrutose. Utilizaram-se doze cavalos sem raça definida, compreendendo quatro machos e oito fêmeas não gestantes, com idade (média ±SD) 7±3,5 anos, pesando 305±35kg e com uma pontuação média de condição corporal de 5±1/9. Os indivíduos elegíveis eram clinicamente saudáveis, sem história prévia de claudicação relacionados ao casco. Após administração de oligofrutose (10g/kg por sonda nasogás-trica), os animais foram divididos em dois grupos: tratado (30mg/kg de DF1681B intravenosa, 6, 12, 18 e 24h após a oligofrutose) e não tratado, que recebeu placebo. Bióp-sias laminares foram realizadas antes e 12, 36 e 72h após a administração de oligofrutose. As amostras foram coradas com ácido periódico de Schiff (PAS) e classificadas de 0-6 de acordo com alterações nas células epidérmicas e na membrana basal. Também determinaram-se as expressões gênicas de IL-1β, CXCL1 e IL-6 por RT-PCR. Testes paramé-tricos e não paramétricos foram utilizados para comparar os momentos em cada grupo (P<0,05). Estatisticamente, os graus PAS e as expressões de IL-1β e IL-6 se elevaram após a indução no grupo não tratado, mas se mantiveram cons- With the hypothesis that blocking chemokine signaling can ameliorate acute laminitis, the aim was to evaluate the therapeutic effect of intravenous DF1681B, a selective antagonist for CXCR1 and CXCR2 (chemokine receptors), in an oligofructose equine laminitis model. To twelve mixed breed clinically healthy hoses with no previous history of hoof-related lameness was administered oligofructose (10g/kg given by nasogastric tube) and divided into two groups: treated (intravenous DF1681B at 30mg/kg 6, 12, 18, and 24h after oligofructose) and non-treated groups. Laminar biopsies were performed before and 12, 36, and 72h after administering oligofructose. Samples were stained with periodic acid-Schiff (PAS) and scored from 0 to 6 according to epidermal cell and basal membrane changes. The IL-1β, IL-6, and CXCL1 RNA expressions were determined by RT-PCR. Parametric and non--parametric tests were used to compare times within each group (P<0.05). The PAS grades and IL-1β and IL-6 RNA expression increased in the non-treated group, but remained constant in the treated horses. In conclusion, DF1681B therapy reduced laminar inflammation and epidermal deterioration in treated horses. CXCR1/2 blockage should be considered therapeutically for equine acute laminitis. tantes nos cavalos tratados. Em conclusão, a terapia por DF1681B reduziu a inflamação laminar e a deterioração epidérmica em equinos submetidos ao modelo de intoxicaç...

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Early laminar events involving endothelial activation in horses with black walnut– induced laminitis

Abstract: Results indicated that endothelial activation and laminar inflammation are early events in laminitis; MMP accumulation likely is a downstream event.

Cited by 85 publications

References 28 publications

Effect of Delayed Digital Hypothermia on Lamellar Inflammatory Signaling in the Oligofructose Laminitis Model

Effect of Delayed Digital Hypothermia on Lamellar Inflammatory Signaling in the Oligofructose Laminitis Model

An update on equine laminitis

Histologic and inflammatory lamellar changes in horses with oligofructose-induced laminitis treated with a CXCR1/2 antagonist

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