Applaggin, an inhibitor of platelet aggregation via binding to the
glycoprotein IIb/IIIa receptor, was examined in an anesthetized canine model of arterial
thrombosis formation secondary to arterial wall injury. Both carotid arteries were isolated and instrumented with flow probes, intravascular anodal
electrodes and adjustable constrictors. The right carotid artery was injured initially and served as the control response to vessel wall injury in each animal, whereas the left carotid was injured after
applaggin administration (1.0 mg/kg, i.v.).
Arterial occlusion in the control vessel occurred in each of seven animals. Time for occlusive
thrombus development was 125.6 +/- 15.2 min. One of the seven left carotid arteries occluded after
applaggin.
Thrombus weight was greater in control vessels (44.2 +/- 7.0 mg) vs.
thrombus weight after
applaggin (11.2 +/- 2.4 mg). Cyclic flow variations occurred in all control arteries before development of an occlusive
thrombus. In contrast, cyclic flow variations were observed only in two of seven vessels injured after
applaggin. One of the latter vessels developed an occlusive
thrombus. Platelet counts, heart rate and blood pressure were unaltered over the course of the experimental protocol. Ex vivo platelet aggregation to
arachidonic acid was examined before and after
applaggin administration. Platelet-rich plasma from animals having initial normal baseline aggregation no longer aggregated 30 min after administration of
applaggin. Aggregation returned to normal within 3 hr.
Applaggin binds to stimulated and unstimulated platelets and two classes of binding sites were identified. The results demonstrate that
applaggin possesses an antithrombotic effect in the experimental model of canine
carotid artery thrombosis.