PLATELET-ACTIVATING-FACTOR AND NOT THROMBOXANE A(2) IS AN IMPORTANT MEDIATOR OF ENDOTOXIN-INDUCED PLATELET-AGGREGATION IN EQUINE HEPARINIZED WHOLE-BLOOD IN-VITRO

Endotoxin has previously been shown to induce platelet aggregation in equine heparinised whole blood This study aimed to determine whether p latelet-activating factor or products of cyclooxygenase metabolism (th romboxane A(2) or prostaglandins) were important in mediating the resp onse of platelets to endotoxin The effects of the following drugs on e ndotoxin-induced aggregation were investigated: aspirin, flunixin megl umine and carprofen (non-steroidal anti-inflammatory drugs); CV-3988 a nd WEB2086 (platelet-activating factor receptor antagonists); quinacri ne (phospholipase A(2) inhibitor). The effects of quinacrine on platel et aggregation in citrated platelet-rich plasma induced by ADP and pla telet-activating factor were also investigated CV-3988 and WEB2086 cau sed a concentration-dependent inhibition of endotoxin-induced aggregat ion The non-steroidal anti-inflammatories were without effect except f lunixin meglumine which produced a small inhibition of endotoxin-induc ed aggregation Quinacrine had a similar effect to the platelet-activat ing factor antagonists, but also non-competitively inhibited platelet aggregation in citrated platelet-rich plasma It is concluded that plat elet-activating factor is a critical mediator of endotoxin-induced pla telet aggregation in the horse, bur that products of cyclooygenase met abolism are not of importance.