Prevention of experimental carotid artery thrombosis by applaggin.
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.
Rote
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WE
University of Michigan Medical School, Department of Pharmacology, Ann Arbor.
Mu
D X
DX
Roncinske
R A
RA
Frelinger
A L
AL
Lucchesi
B R
BR
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002341:Carotid Artery Thrombosis / Q000517:prevention & control*; D003435:Crotalid Venoms / Q000097:blood / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D007700:Kinetics; D008297:Male; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*
D003435:Crotalid Venoms; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; C041603:Agkistrodon platelet aggregation inhibitor