In vivo evaluation of antiplatelet agents in gerbil model of carotid artery thrombosis.
OBJECTIVE
Antiplatelet agents are widely used for the prevention of ischemic stroke. However, their effects on thrombus formation have rarely been evaluated in experimental animals in vivo. We introduce methods for evaluating antithrombotic action in gerbils and the effects of several antiplatelet agents on thrombus formation.


METHODS
In gerbils 8 to 10 weeks of age, we tightly compressed the unilateral common carotid artery for 2 minutes using the device prepared for this purpose to damage the endothelium. Thrombus formation in the damaged artery was observed directly through the microscope for 30 minutes. In six animals, the damaged artery was examined immediately after the experiments by electron microscopy. We studied the effects of antiplatelets by injecting the drugs intravenously 10 minutes before endothelial damage.


RESULTS
In control studies, 70% to 90% of animals developed thrombi after arterial compression. The electron microscopic examination displayed endothelial damage in association with platelet thrombus at the damaged site. Administration of 2 mg/kg aspirin, 3 and 10 mg/kg ticlopidine, and 0.3 and 1.0 mg/kg ibudilast, a novel prostacyclin accelerator, decreased the frequency of thrombus formation significantly, whereas 20 mg/kg aspirin and 20 mg/kg dipyridamole failed to decrease thrombus formation.


CONCLUSIONS
This model is considered useful for evaluating the antithrombotic effects of drugs because of its feasibility and high reproducibility. The present results support the view that a lower dose of aspirin may prevent cerebral vascular accidents as efficiently as a higher dose of aspirin.
Nishimura
H
H
Fifth Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Naritomi
H
H
Iwamoto
Y
Y
Tachibana
H
H
Sugita
M
M
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D002340:Carotid Artery Diseases / Q000209:etiology / Q000517:prevention & control*; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common / Q000648:ultrastructure; D002561:Cerebrovascular Disorders / Q000517:prevention & control; D004176:Dipyridamole / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000293:injuries / Q000648:ultrastructure; D005240:Feasibility Studies; D005849:Gerbillinae; D007275:Injections, Intravenous; D008297:Male; D008854:Microscopy, Electron; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use; D015203:Reproducibility of Results; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000627:therapeutic use; D007212:Indolizines; D011720:Pyrazoles
D001241:Aspirin; D004176:Dipyridamole; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D013988:Ticlopidine; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles