Abstract
The antithrombotic effects of drugs have rarely been evaluated in experimental animals because of a lack of adequate models. We recently reported a method for inducing endothelial damage in the gerbil common carotid artery, which led to platelet thrombus formation at the site of endothelial injury with a high reproducibility. We evaluated the antithrombotic effects of ibudilast, a cerebral vasodilator with actions potentiating prostacycline (PGI2) activity and aspirin employing this method. In 40 adult male gerbils, a unilateral common carotid artery was squeezed for 2 min employing a device prepared for this purpose to induce endothelial damage. Thrombus formation was subsequently estimated with a microscope for 30 min. 2 mg/kg aspirin, 0.3 mg/kg or 1.0 mg/kg ibudilast, or normal saline as a control was injected intravenously at 10 min prion to the endothelial injury. In control group 70% of animals developed a white thrombus at the site of endothelial injury. 2 mg/kg aspirin significantly reduced the frequency of thrombus formation (10%, p<0.05). 1.0 mg/kg ibudilast reduced the frequency of thrombus formation to the same extent as aspirin (10%, p<0.05), although 0.3 mg/kg ibudilast failed to decrease the thrombus formation (20%, p<0.1). The antiplatelet action of ibudilast was shown to be feeble as compared with that of aspirin, when tested ex vivo. However, the ex vivo evaluation may not accurately reflect the antiplatelet action of drugs which influence the PGI2activity, since PGI2is produced mainly in the endothelium. The present in vivo method appears to be useful for assessing the antiplatelet actions of such drug.
