A GARLIC DERIVATIVE, AJOENE, INHIBITS PLATELET DEPOSITION ON SEVERELYDAMAGED VESSEL WALL IN AN IN-VIVO PORCINE EXPERIMENTAL-MODEL

Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent a ntiplatelet compound isolated from alcoholic extracts of garlic. In vi tro ajoene reversibly inhibits platelet aggregation as well as the rel ease reaction induced by all known agonists. We used a well characteri zed perfusion chamber to study the in vivo effects of ajoene on platel et deposition onto a highly thrombogenic, severely damaged arterial wa ll, obtained by stripping off the intimal layer and exposing tunica me dia. Platelet-vessel wall interaction and the effect of ajoene was stu died under flow conditions of high and low local shear rate that mimic s laminar blood flow in small and medium size arteries (1690 sec(-1) a nd 212 sec(-1)). Our results indicate that administration of ajoene to heparinized animals, significantly prevents thrombus formation at loc al low blood shear rate. Ajoene does not inhibit binding of vWF to GPI b, therefore, it does not affect platelet adhesion. In fact, although ajoene impairs fibrinogen and vWF (less efficient) binding to GPlIb/II Ia, it does not totally inhibits platelet deposition to the substrates at any of the shear rates used in this study. Our present results, un der in vivo flow conditions and in the presence of physiological calci um levels, suggest that ajoene may be potentially useful for the acute prevention of thrombus formation induced by severe vascular damage, m ainly in arterial sites with local low shear rates.