Early endotoxin-mediated haemostatic and inflammatory responses in the clopidogrel-treated pig

Abstract

We have previously shown that the thrombin inhibiting agent melagatran markedly prolongs aPTT and counteracts creatinine increase in endotoxemic pigs. Against this background the effects of the platelet-inhibiting agent, clopidogrel on basic haemostatic, inflammatory and physiological variables were evaluated during porcine endotoxemia. Clopidogrel (10 mg/kg) or saline was randomly injected i.v. 30 min before start of a 6-h continuous infusion of endotoxin in 12 anaesthetised pigs. Another three pigs were given clopidogrel but not endotoxin. Clopidogrel did not affect physiological variables, formation of activated platelet microparticles, PK, aPTT, platelet count, plasma fibrinogen, TNF-α, or IL-6 during porcine endotoxemia. Although renal function, as evaluated by creatinine clearance (CLcr) deteriorated significantly (P = 0.01) in the saline–endotoxin, but not in the clopidogrel–endotoxin group, there was no significant difference between the saline–endotoxin and the clopidogrel–endotoxin groups. Renal biopsies were marked with a FITC-labelled chicken anti-fibrinogen antibody detecting fibrinogen and platelet bound fibrinogen, as a marker of porcine platelet activation, and examined by light microscopy. Evaluation of these immunohistochemical slides did not indicate that clopidogrel, significantly reduced the amount of intrarenal fibrin or fibrinogen depositions. Besides a trend to preserve renal function, clopidogrel did not affect haemodynamics or the coagulatory and inflammatory responses in porcine endotoxemia.

• Clopidogrel
• creatinine clearance
• fibrin
• immunohistochemistry
• platelet
• septic shock