Evaluation of plasma angiopoietin-2 and vascular endothelial growth factor in healthy dogs and dogs with systemic inflammatory response syndrome or sepsis

J Vet Intern Med. 2019 Mar;33(2):569-577. doi: 10.1111/jvim.15369. Epub 2018 Dec 21.

Abstract

Background: Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) are regulators of endothelial permeability.

Objective: Plasma concentrations of Ang-2 and VEGF are increased in dogs with systemic inflammatory response syndrome (SIRS) and sepsis and are correlated with disease severity and outcome.

Animals: Healthy dogs (n = 18) and client-owned dogs with SIRS (n = 34) or sepsis (n = 25).

Methods: Prospective observational study. Ang-2 and VEGF concentrations in admission plasma samples were compared between healthy dogs and dogs with SIRS or sepsis, and between survivors and non-survivors. Correlations with the acute patient physiologic and laboratory evaluation (APPLEfast ) disease severity score were examined.

Results: Median Ang-2 was significantly higher in dogs with SIRS (19.3; interquartile range [IQR]: 8.6-25.7 ng/mL) and sepsis (21.2; IQR: 10.3-30.1 ng/mL) compared to healthy dogs (7.6; IQR: 6.7-9.8 ng/mL). Ang-2 was significantly higher in non-survivors (24.1; IQR: 11.9-50.0 ng/mL) than survivors (10.2; IQR: 7.2-21.5 ng/mL) but did not correlate with the APPLEfast score. Admission Ang-2 predicted negative outcome in dogs with SIRS and sepsis with reasonable accuracy (area under the curve [AUC]: 0.75, confidence interval [CI]: 0.59-0.85; sensitivity: 0.5, CI: 0.29-0.71; specificity: 0.87, CI: 0.75-0.95); differentiation between sepsis and SIRS was poor (AUC: 0.58). Plasma VEGF was significantly higher in dogs with sepsis (45; IQR: 14-107.5 pg/mL) than in dogs with SIRS (3.3; IQR: 0-35.6 pg/mL) or healthy dogs (0; IQR: 0 pg/mL; P = 0.008). VEGF was significantly (P = .0004) higher in non-survivors (34.5; IQR: 0-105.7 pg/mL) than in survivors (0; IQR: 0-55.2 pg/mL). The ability of VEGF to predict a negative outcome was poor.

Conclusions and clinical importance: Ang-2 may represent a useful additional prognostic marker in dogs with SIRS.

Keywords: APPLEfast score; biomarker; canine; inflammation; outcome; prognostic.

Publication types

  • Observational Study, Veterinary

MeSH terms

  • Angiopoietin-2 / blood*
  • Animals
  • Biomarkers / blood*
  • Dog Diseases / blood*
  • Dogs / blood*
  • Female
  • Male
  • Prospective Studies
  • Sensitivity and Specificity
  • Sepsis / blood
  • Sepsis / veterinary*
  • Systemic Inflammatory Response Syndrome / blood
  • Systemic Inflammatory Response Syndrome / veterinary*
  • Vascular Endothelial Growth Factor A / blood*

Substances

  • Angiopoietin-2
  • Biomarkers
  • Vascular Endothelial Growth Factor A