Abstract
Background: The degree of systemic inflammation, reperfusion injury and endothelial activation are potentially important determinants of clinical outcomes in dogs with gastric dilatation volvulus (GDV).Objective: To evaluate plasma concentrations and kinetics of inflammatory markers in dogs with GDV over a time frame of 48 h, and to compare to healthy dogs.Design and Setting: Prospective, observational cohort study in client-owned dogs with GDV.Materials and Methods: Fifteen dogs with GDV and 9 healthy control dogs were enrolled. Plasma concentrations of interleukin (IL)-6, IL-7, IL-8, IL-10, IL-15, IL-18, interferon gamma (IFN-γ), keratinocyte chemotactic-like, monocyte chemotactic protein (MCP)-1, Angiopoietin (Ang)-2, and C-reactive protein (CRP) were measured at admission (prior any therapeutic intervention, (T0), immediately after surgery (T1), 24 ± 4 h (T24), and 48 ± 4 h (T48) post-surgery. Cytokines were measured using multiplex magnetic bead assay. Plasma Ang-2 was measured with a commercial human ELISA test kit validated for dogs.Results: Dogs with GDV had significantly higher plasma concentrations of IFN-γ and IL-10 compared to healthy control dogs at all time points. Concentrations of IL-6 were significantly higher at T1 and T24, concentrations of MCP-1 at T24, and concentrations of CRP at T24 and T48. A significant increase between T0 and T1 was found for IL-6, IL-10, and CRP, between T1 and T24 for IL-8, IFN-γ, MCP-1, and CRP, and between T24 and T48 for IL-15, Ang-2, and CRP. A significant decrease between T0 and T1 was found for IL-7, IL-8, IL-15, IL-18, and Ang-2; between T1 and T24 for IL-6 and KC-like; and between T24 and T48 for IL-6.Conclusion: In GDV dogs, a mild pro-inflammatory reaction was present at admission, which peaked immediately after and up to 24 h post-surgery, mainly represented by IL-6, IFN-γ, MCP-1, and CRP, and which decreased at T48. In addition, the anti-inflammatory IL-10 was increased in GDV dogs at all time points.
Highlights
Canine gastric dilatation volvulus (GDV) is a life-threatening condition characterized by gastric displacement and cardiovascular shock
A significant increase between T0 and T1 was found for IL-6 (P = 0.020), IL-10 (P = 0.001), and C-reactive protein (CRP) (P = 0.005); between T1 and T24 for IL-8 (P = 0.001), IFN-γ (P = 0.012), monocyte chemotactic protein (MCP-1) (P = 0.021), and CRP (P = 0.0002); and between T24 and T48 for IL-15 (P = 0.039), Ang-2 (P = 0.009), and CRP (P = 0.009) (Table 2, Figure 1)
Concentrations of admission IL-6 and MCP-1 were higher in dogs with moderate/severe gastric wall changes, but this difference did not reach statistical significance (Figures 2A,C). In this present study we investigated the concentrations and kinetics of inflammatory cytokines, Ang-2, and CRP in dogs with GDV at 4 time points and compared them to plasma concentrations measured at a single time point in healthy control dogs
Summary
Canine gastric dilatation volvulus (GDV) is a life-threatening condition characterized by gastric displacement and cardiovascular shock. Subsequent systemic hypoperfusion, gastric ischemia and reperfusion, gastric wall necrosis, and gastro-intestinal bacterial translocation trigger an inflammatory response leading to a systemic inflammatory response syndrome (SIRS) [1] Triggers of this sterile inflammation are damageassociated molecular patterns (e.g., molecules released from necrotic cells) and microbial pathogen-associated molecular patterns [2]. The cascade of IRI involves activation of neutrophils, platelets, cytokines, reactive nitrogen species, reactive oxygen species (ROS), the coagulation system, the endothelium, and the xanthine-oxido-reductase enzyme system [3]. All these factors may potentially lead to irreversible organ damage and failure [1, 3, 4]. The degree of systemic inflammation, reperfusion injury and endothelial activation are potentially important determinants of clinical outcomes in dogs with gastric dilatation volvulus (GDV)
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