SIN-1 PARTIALLY AND RGDS TOTALLY COUNTERACTS PLATELET-AGGREGATION AS ASSESSED IN-VITRO BY 2 INDEPENDENT WHOLE-BLOOD METHODS

The cyclic GMP stimulant SIN-1 and the GP IIB/IIIA receptor antagonist RGDS were compared with regard to platelet antiaggregatory effects as measured in vitro by filtragometry and by whole blood aggregometry. I n filtragometry platelet aggregation is measured as the time to partia l occlusion of a filter in the test unit. beta-thromboglobulin concent rations increased over the filter (p<0.002) indicating that in filtrag ometry part of the mechanism of aggregation could be platelet activati on across the filter. In whole blood aggregometry platelet aggregation is induced by a chemical stimulant. As tested in blood from healthy v olunteers, linear dose-effect relations were found with both methods, for SIN-1 in the 10(-7)-10(-6) M range (p<0.02, filtragometry and p<0. 05, whole blood aggregometry) and for RGDS in the 10(-5)-10(-4) M rang e (p<0.0001, filtragometry and p<0.02, whole blood aggregometry). At t he highest dose RGDS totally counteracted platelet aggregation in both test systems. Maximal SIN-1 platelet antiaggregatory effects were les s (p<0.04, filtragometry and p<0.01, whole blood aggregometry) than fo r RGDS. SIN-1 concentrations in the 10(-4) M range had no further anti aggregatory effects. In conclusion, with two principally different met hods for the assessment of whole blood platelet aggregation, SIN-1 was found to be a partial antagonist while RGDS a total antagonist.