Effect of Continuous Digital Hypothermia on Lamellar Inflammatory Signaling When Applied at a Clinically‐Relevant Timepoint in the Oligofructose Laminitis Model

Background 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. Hypothesis/Objectives 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). Animals 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, CXCL 1, MCP 2, 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 and Clinical Importance 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.