Antithrombotic Effect of Ticlopidine on Occlusive Thrombi of Small Coronary Arteries in (NZWxBXSB)F1 Male Mice with Myocardial Infarction and Systemic Lupus Erythematosus

Abstract
We examined the antithrombotic effect of ticlopidine on occlusive thrombi of small coronary arteries in (NZWxBXSB)F1 [(WxB)F1] male mice with myocardial infarction (MI) and systemic lupus erythematosus (SLE). Ticlopidine (3 and 10 mg/kg) was given to the mice as an additive to a standard laboratory diet from the time the mice were aged 16-24 weeks. The higher dose of ticlopidine significantly increased survival rate of the mice. In mice that received 10 mg/kg ticlopidine, the incidence of MI, the percentage of MI area (%MI), and the incidence and number of small coronary arteries with significant stenosis were significantly lower than in controls. The stenosed lesions were divided into occlusive thrombi related to acute MI and intimal thickening related to old MI. No mice had evidence of significant stenosis or thrombosis in the extramyocardial coronary arteries. Glomerulonephritis, blood urea nitrogen (BUN), and circulating immune complexes were not significantly different among the three groups. A high dose of ticlopidine prevented small coronary artery disease and MI and increased the survival of (WxB)F1 male mice, suggesting that this agent has an antithrombotic effect on occlusive thrombi of the small coronary arteries in such mice.