P-Selectin Antagonism Causes Dose-dependent Venous Thrombosis Inhibition

Daniel D. Myers; Robert Schaub; Shirley K. Wrobleski; Frank J. Londy; Beverly A. Fex; Amy M. Chapman; Lazar J. Greenfield; Thomas W. Wakefield

doi:10.1055/s-0037-1615622

Thrombosis and Haemostasis, Table of Contents

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

Daniel D. Myers

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

,

Robert Schaub

³Genetics Institute, Andover, Massachusetts, USA

,

Shirley K. Wrobleski

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

,

Frank J. Londy

²Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan

,

Beverly A. Fex

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

,

Amy M. Chapman

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

,

Lazar J. Greenfield

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

,

Thomas W. Wakefield

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

› Author Affiliations

Abstract

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.

Keywords

Selectin - antagonism - thrombosis - inflammation - venous

Full Text

References

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