Aurintricarboxylic acid reduces platelet deposition in stenosed and endothelially injured rabbit carotid arteries more effectively than other antiplatelet interventions.
In the present study we tested the effects of different antithrombotic interventions on platelet deposition in experimentally-stenotic rabbit carotid arteries with endothelial injury. Platelet deposition, quantitated by labeling autologous platelets with 111In-oxine, was significantly reduced compared to control animals by all interventions tested, i.e., R 68070, a drug with thromboxane A2 synthase and receptor blocking properties, BN 52021, a PAF receptor antagonist, aurintricarboxylic acid (ATA), an inhibitor of platelet glycoprotein (Gp) Ib/von Willebrand factor (vWf) interaction, AZ-1, a monoclonal antibody against rabbit GP IIb/IIIa, the platelet receptor for fibrinogen, and AP-1, a monoclonal antibody against rabbit tissue factor. ATA was significantly more effective than all the other interventions in reducing platelet deposition in the stenotic vessels. We conclude that inhibition of Gp Ib/vWf interaction may be a more suitable target for antithrombotic therapy under conditions of high shear stress, like those produced in this model.
Golino
P
P
Department of Internal Medicine, 2nd School of Medicine, University of Naples, Italy.
Ragni
M
M
Cirillo
P
P
Pascucci
I
I
Ezekowitz
M D
MD
Pawashe
A
A
Scognamiglio
A
A
Pace
L
L
Guarino
A
A
Chiariello
M
M
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D001783:Blood Flow Velocity; D016893:Carotid Stenosis / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007205:Indium Radioisotopes; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000037:antagonists & inhibitors; D011817:Rabbits; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D007205:Indium Radioisotopes; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D001312:Aurintricarboxylic Acid; D013930:Thromboxane-A Synthase