Protective effect of ticlopidine on experimentally induced peripheral arterial occlusive disease in rats

Abstract

An experimental peripheral arterial occlusive disease was induced in rats by injection of sodium laurate into the femoral artery. The laurate injection caused a transient ischemic paleness of the paw followed by gangrene extending from the fingers to the whole paw in about 6 days. The affected part of the paw was then mummified and fell off after 10 to 15 days of the laurate injection. Histological examination revealed various lesions of the peripheral arteries of the paw accompanying thrombus formation. The early vascular lesions included degeneration of the endothelium and edematous swelling of the intima and media with some fibrinoid deposits. In the progressive phase, many small arteries were occluded or narrowed by thrombi, which were advanced into fibrosis or organization in the later stages. These vascular lesions resembled, at least in part, those reported with thromboangitis obliterans (TAO) in humans. Treatment of the rats with an anti-platelet agent, ticlopidine, resulted in a marked protection of the macroscopic changes in the paw after the laurate injection without any effects on coagulo-fibrinolytic parameters. A similar protection of the disease was also observed with thrombocytopenic rats. These findings suggest a major participation of platelets in progression of the disease.