COMPARATIVE EFFECTS OF ANTIPLATETLET AGENTS AS ADJUNCTS TO TISSUE-PLASMINOGEN ACTIVATOR IN A DOG-MODEL OF OCCLUSIVE CORONARY-THROMBOSIS

1 This study compares a cyclo-oxygenase inhibitor (aspirin), a 5-HT2 a ntagonist (ZM170809) and a combined thromboxane synthase inhibitor/rec eptor antagonist (ZD1542) as adjuncts to tissue plasminogen activator (rt-PA). 2 Application of an anodal current (332 +/- 4.1 mu A) to the stenosed left circumflex coronary artery of 20 anaesthetized dogs prod uced a stable platelet-rich occlusive thrombus. 3 After initial i.v. a dministration of recombinant human tissue type plasminogen activator ( rt-PA, 3 mg bolus + 2 mg kg(-1) h(-1) for 30 min) thrombolysis occurre d in 15 out of 20 dogs. All 15 dogs reoccluded. 4 The second i.v. admi nistration of rt-PA in the presence of either aspirin, ZM170809, ZD154 2 or saline resulted in thrombolysis in all 20 dogs. 5 Both the combin ed thromboxane synthase inhibitor/receptor antagonist (ZD1542) and 5-H T2 antagonist (ZM170809) significantly (P<0.05) reduced the time taken to lyse the thrombus compared with the saline group. The times were 1 4.4 +/- 2.7 min, 18.0 +/- 3.9 min and 36.8 +/- 6.2 min for ZD1542, ZM1 70809 and saline respectively. 6 Aspirin did not offer any additional benefit to using rt-PA alone. The times to thrombolysis were 36.8 +/- 8.4 min for aspirin and 36.8 +/- 6.2 min for the saline group. 7 The n umber of dogs in which the circumflex coronary artery reoccluded withi n 60 min of terminating the second infusion of rt-PA were five for sal ine, four for aspirin, two for ZD1542 and two for ZM170809. 8 These re sults indicate that both ZD1542 and ZM170809 are more effective adjunc ts than aspirin in thombolysis and may provide an improvement in curre nt clinical practice.