PLATELET-ADHESION FOLLOWING THE ADMINISTRATION OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR AND ITS REVERSAL BY VITAMIN-E IN RATS

Thrombolytic therapy is known to induce platelet-related side effects. We used a parallel-plate flow chamber, which was connected to the fem oral artery of the rat, to measure platelet adhesion ex vivo. A collag en-coated arterioarterial shunt between two carotid arteries was used to measure shunt patency duration as an index of antithrombotic effica cy. Tissue-type plasminogen activator (t-PA), vitamin E, and the combi nation of these two were intravenously administered for 60 min. Measur ements were performed before drug administration, and at 30, 60, 120 m in after the initiation of drug infusion. Our results indicated that ( 1) treatments with t-PA or t-PA/vitamin E prolonged the time to shunt occlusion at 30 and 60 min; (2) t-PA enhanced platelet adhesion at 60 and 120 min; (3) vitamin E tended to reduce platelet adhesion; (4) t-P A/vitamin E reduced the t-PA-enhanced platelet adhesion, (5) at the hi gh-density area of platelet adhesion under t-PA treatment, the adheren t platelets demonstrated severe morphological changes which could be b locked by vitamin E. These data suggest that t-PA map enhance platelet adhesion in rats and that this adverse effect can be suppressed by co -administration of vitamin E.