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(Stroke. 1996;27:1099-1104.)
© 1996 American Heart Association, Inc.

Articles

In Vivo Evaluation of Antiplatelet Agents in Gerbil Model of Carotid Artery Thrombosis

Hiroyuki Nishimura, MD, PhD; Hiroaki Naritomi, MD, PhD; Yasumichi Iwamoto, MD; Hisao Tachibana, MD, PhD Minoru Sugita, MD, PhD

From the Fifth Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, and the Division of Cerebral Circulation Research, National Cardiovascular Center, Osaka (H. Naritomi), Japan.

Background and Purpose 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.

Key Words: aspirin • endothelium • thrombosis • ticlopidine • gerbils

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