Effect of recombinant activated protein C and low-dose heparin on neutrophil-endothelial cell interactions in septic shock.
OBJECTIVE
To examine the effects of recombinant activated protein C (rhAPC) and low-dose heparin on neutrophil-platelet-endothelial cell interactions in septic shock.


METHODS
Controlled experiments using phase contrast microscopy to study neutrophil, platelet, and endothelial cell interactions in flowing cell suspensions under simulated physiologic conditions.


METHODS
University research laboratory.


METHODS
Adult patients with septic shock and normal volunteers.


METHODS
Neutrophils and platelets removed from control subjects were stimulated with plasma and serum from 21 patients in septic shock and perfused over endothelial cells. Activated protein C, low-dose heparin, and low-dose heparin with rhAPC were added to cells suspended in septic plasma. Neutrophil rolling velocity and the number of neutrophils adherent to endothelial cells and in aggregates were determined. Flow cytometric analysis of CD11b/CD63 cells was used to identify platelet-neutrophil aggregates.


RESULTS
Activated protein C significantly decreased neutrophil adhesion and aggregation and increased rolling velocity in cells stimulated with both septic serum and septic plasma. Significant decreases in platelet-neutrophil aggregates induced by septic plasma were also observed. Low-dose heparin alone had no effects on these variables. The addition of low-dose heparin to cells suspended in septic plasma and rhAPC attenuated the benefits observed with rhAPC alone in each of these variables.


CONCLUSIONS
These data suggest that the in vitro addition of rhAPC decreases sepsis-induced interactions between isolated platelets, neutrophils, and endothelial cells. Low-dose heparin attenuates the benefits observed with rhAPC. The changes in neutrophil-endothelial cell interactions demonstrated with rhAPC may play a role in preserving microvascular patency in patients with septic shock.
Kirschenbaum
Linda A
LA
Department of Medicine, New York Medical College, Valhalla, New York, USA.
Lopez
Wilma Correa
WC
Ohrum
Patricia
P
Tsen
Anita
A
Khazin
John
J
Astiz
Mark E
ME
D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D005434:Flow Cytometry; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects*; D011486:Protein C / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012772:Shock, Septic / Q000473:pathology*
D000925:Anticoagulants; D011486:Protein C; D011994:Recombinant Proteins; D006493:Heparin