Antithrombin reduces monocyte and neutrophil CD11b up regulation in addition to blocking platelet activation during extracorporeal circulation.
BACKGROUND
Patients undergoing cardiac surgery requiring cardiopulmonary bypass develop a systemic inflammatory reaction. Antithrombin III (AT) has anticoagulant effects but also shows evidence of anti-inflammatory activity. The aim of this study was to examine whether exogenous AT could reduce white blood cell activation (CD11b up regulation or elastase release), in addition to inhibiting platelet (PLT) activation and fibrin generation, during simulated cardiopulmonary bypass (sCPB), undertaken in the absence of endothelium.


METHODS
sCPB was carried out with minimally heparinized (2 U/mL) human blood for 90 minutes in controls and with supplementation by low-dose (1 U/mL) and high-dose (5 U/mL) AT.


RESULTS
High-dose AT blunted thrombin generation during sCPB (prothrombin fragment 1.2); both doses significantly inhibited thrombin activity (fibrinopeptide A). Complement activation (C3a and C5b-9) was unaffected by AT. High-dose AT inhibited PLT activation (P-selectin expression and P-selectin-dependent monocyte-PLT conjugate formation). AT supplementation at the higher dose significantly abrogated monocyte and neutrophil CD11b up regulation and neutrophil elastase release.


CONCLUSIONS
In addition to anticoagulant and anti-PLT effects, pharmacologic AT doses significantly blunted monocyte and neutrophil CD11b up regulation and neutrophil elastase release during sCPB, independent of endothelial effects. These data provide evidence for the direct anti-inflammatory activity of AT that has clinical relevance for CPB complications.
Rinder
Christine S
CS
Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06520-8051, USA. christine.rinder@yale.edu
Rinder
Henry M
HM
Smith
Michael J
MJ
Fitch
Jane C K
JC
Tracey
Jayne B
JB
Chandler
Wayne L
WL
Rollins
Scott A
SA
Smith
Brian R
BR
D000990:Antithrombin III / Q000494:pharmacology*; D039481:CD11b Antigen / Q000187:drug effects* / Q000235:genetics; D005112:Extracorporeal Circulation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D039481:CD11b Antigen; D010975:Platelet Aggregation Inhibitors; D000990:Antithrombin III