Ex Vivo Effects of Acetylsalicylic Acid, Sulfinpyrazone and Dipyridamole on Platelet Adhesion and Thrombus Formation in Flowing Native and Anticoagulated Blood
Potential platelet inhibitors are usually tested ex vivo by investigating platelet function in vitro after drug ingestion and subsequent blood collection into citrate. The purpose of the present study was to determine whether and how citrate anticoagulation interferes with possible drug actions in rabbits. Platelet adhesion and thrombus formation on subendothelium were compared after perfusion at 1300 sec-1 wall shear rate of native blood and of blood anticoagulated with citrate, heparin or heparin plus citrate. Results. 15 mM citrate in plasma caused significant reduction of aggregation, thrombus volume and thrombus height; adhesion was concomitantly increased. Heparin (500 U/kg) had no effect on adhesion and thrombus dimensions. Treatment of rabbits with acetylsalicylic acid or sulfinpyrazone (2x100 µmol/kg) caused a significant reduction of thrombus volume and thrombus height in the presence of citrate. However, no drug effects were observed after perfusion of native or heparinized blood of the same rabbits. Equimolar doses of dipyridamole were always without effect. Conclusion. Low citrate concentrations (1) inhibit thrombus growth, (2) enhance thrombus breakdown,(3) secondarily increase adhesion and (4) strongly enhance a possible inhibitory effect of acetylsalicylic acid and sulfinpyrazone on thrombus growth and/or breakdown.