Thromb Haemost 2001; 85(03): 423-429
DOI: 10.1055/s-0037-1615622
Scientific and Standardization Committee Communication
Schattauer GmbH

P-Selectin Antagonism Causes Dose-dependent Venous Thrombosis Inhibition

Authors

  • Daniel D. Myers

    1   Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, Unit for Laboratory Animal Medicine
  • Robert Schaub

    3   Genetics Institute, Andover, Massachusetts, USA
  • Shirley K. Wrobleski

    1   Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, Unit for Laboratory Animal Medicine
  • Frank J. Londy

    2   Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan
  • Beverly A. Fex

    1   Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, Unit for Laboratory Animal Medicine
  • Amy M. Chapman

    1   Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, Unit for Laboratory Animal Medicine
  • Lazar J. Greenfield

    1   Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, Unit for Laboratory Animal Medicine
  • Thomas W. Wakefield

    1   Jobst Vascular Laboratory, Section of Vascular Surgery, Department of Surgery, Unit for Laboratory Animal Medicine
Further Information

Publication History

Received 26 July 2000

Accepted after revision 28 September 2000

Publication Date:
08 December 2017 (online)

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Summary

Inhibition of P-selectin by antibody or selectin antagonist decreases inflammation and thrombosis. This study evaluates the dose-response relationship using a selectin receptor antagonist. Eight male baboons (Papio anubis) underwent inferior vena caval thrombosis using a 6 h balloon occlusion model. Three animals received 500 μg/kg P-selectin antagonist (rPSGL-Ig) and five 1 mg/kg rPSGL-Ig with or without a non-anticoagulant dose of Dalteparin. These animals were compared to our published results in this model with 4 saline controls and 8 animals that received 4 mg/kg rPSGL-Ig. A statistically significant dose-response relationship existed between rPSGL-Ig dose and thrombosis (p < 0.01), and between rPSGL-Ig dose and spontaneous recanalization (p < 0.05). Inflammatory assessment revealed decreased gadolinium enhancement in all rPSGL-Ig groups compared to previously reported control, despite no significant differences in inflammatory cell extra-vasation. No dose of rPSGL-Ig caused anticoagulation. Selectin antagonism results in a dose-dependent decrease in thrombosis and increase in spontaneous recanalization.