Prostaglandins E 2 And F 2α as Inflammatory and Vasoactive Mediators in Black Walnut Heartwood Extract-Induced Equine Laminitis

Abstract

s Vol 30, No 2 (2010) 95 TAKE HOME MESSAGE Elastase concentrations are increased in the integument of horses during the developmental phase of BWHE-induced laminitis. INTRODUCTION Current evidence suggests the involvement of neutrophils and myeloperoxidase (MPO), a strong oxidative enzyme in the development of laminitis. Elastase is a protease recognized as a component of inflammatory disorders. Neutrophil elastase concentrations were measured in plasma, skin and laminar tissues from control horses and horses given BWHE MATERIALS & METHODS (INCLUDING STATISTICAL ANALYSES) The study included 4 groups, a control group (water) and 3 experimental groups (BWHE). Plasma was obtained hourly until euthanasia of BWHE-treated horses at 1.5 (n 1⁄4 5), 3 (n 1⁄4 6), and 12 hours (n 1⁄4 10 plasma/n 1⁄4 6 tissue) and control horses at 12 hours (n 1⁄4 7 plasma/ n 1⁄4 5 tissue). Elastase concentrations were determined via ELISA. Log-transformed data were analyzed with 1-way ANOVA (tissues) and unpaired t-test (plasma); significance was set at P < 0.05. RESULTS Plasma elastase concentrations in the BWHE group were significantly higher at 6, 8 and 10h compared to the control group. Concentrations in skin and laminar tissue were significantly higher at 3 and 12h in the BWHE group. Elastase concentrations were significantly higher in skin than in lamina at 12h in BWHE group. DISCUSSION Increased elastase concentrations are consistent with dynamic changes in circulating leukocytes in horses given BWHE. Collectively, MPO and elastase have the potential to cause significant tissue damage during the development of laminitis. CLINICAL RELEVANCE Elastase may become an important target as new treatments for laminitis are developed. CONCLUSION Elastase concentrations increase in the integumentary system during the development of laminitis and may participate in the disintegration of the hoof basal membrane. Prostaglandins E2 And F2a as Inflammatory and Vasoactive Mediators in Black Walnut Heartwood Extract-Induced Equine Laminitis Erik Noschka, James N. Moore, John F. Peroni, Stephen J. Lewis, and Tom P. Robertson, Department of Large Animal Clinical Sciences (Noschka), Virginia Maryland Regional College of Veterinary Medicine Duck Pond Drive, Blacksburg, VA, 24071, Department of Physiology and Pharmacology, Institute of Comparative Medicine (Robertson, Moore, T Lewis, Peroni), and Department of Large Animal Medicine (Robertson, Moore, Peroni), College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389, and Department of Pediatrics (S Lewis) University of Virginia, College of Medicine, Charlottesville, VA 22908 TAKE HOME MESSAGE The increases in plasma levels of prostaglandins E2 (PGE2) and F2a at an early stage of laminitis are consistent with systemic inflammatory events and alterations in laminar microvascular function. INTRODUCTION Links between the inflammatory and vascular events during the prodromal stages of laminitis have yet to be identified. The aim of this study was to provide initial insights into the role that PGE2 and F2a may play in the development of laminitis induced by black walnut heartwood extract (BWHE). MATERIALS AND METHODS Blood samples were collected before and after administration of either water (control horses) or BWHE for white blood cell counts and plasma concentrations of PGE2 and F2a. Laminar tissue was collected for the isolation of laminar vessels, and responses of these vessels to PGE2 and F2 a were determined. The data were analyzed by repeated measures analysis of variance (ANOVA). Differences between individual means were identified by Student’s modified t-test using the Bonferroni correction for multiple comparisons between means using the error mean square term from the ANOVA. RESULTS Plasma levels of PGE2 and F2a increased transiently and coincided with the nadir in white blood cell counts in BWHE horses. PGE2 elicited small dilator responses in laminar veins from control horses, but elicited a small constrictor response in laminar veins from BWHE horses. PGF2a was 96 Abstracts Vol 30, No 2 (2010) a potent contractile agonist for laminar veins, whereas laminar arteries were unresponsive. DISCUSSION PGE2 elicited vascular responses in laminar vessels in control and BWHE horses may be explained by different receptor populations and alterations in laminar tissues in BWHE horses. PGF2a selectively constricted laminar veins, and may play a role in the vascular dysfunction that characterizes acute laminitis. CLINICAL RELEVANCE The use of anti-inflammatory drugs in acute laminitis is supported by the results of this study. The effects of these drugs on responses of laminar microvessels to other PGs need to be determined. CONCLUSION Specific prostanoids, such as PGE2 and F2a, may be viable targets for the development of more effective therapeutic regimens for the treatment of equine laminitis. Proliferative Effects of Insulin on Equine Lamellar Epithelial Cells Mediated By the IGF-1 Receptor S.R. Bailey and S. Chockalingham, Faculty of Veterinary Science, University of Melbourne, Victoria 3010,