ACADESINE REDUCES THE FREQUENCY OF CORONARY-ARTERY REOCCLUSION FOLLOWING RT-PA INDUCED THROMBOLYSIS IN THE DOG

Acadesine is a ribose-substituted imidazole with antithrombotic proper ties mediated by adenosine. In view of the beneficial effects of antip latelet agents on thrombolysis and post-thrombolytic reocclusion, we s tudied the effects of acadesine on t-PA induced coronary reperfusion a nd continued patency in anesthetized dogs with electrically-induced co ronary artery thrombosis. In 4 groups of dogs we examined the effects of saline and 3 doses of acadesine (0.5, 1.0, 2.0 mg/kg/min, i.v.) on time to reperfusion, and incidence and time to reocclusion following i nfusion of t-PA (10 mu g/kg/min, i.v.). Acadesine had no effect on tim e to reperfusion, but significantly (p<0.05) reduced the incidence of reocclusion and prolonged the time to reocclusion at the highest dose tested. In saline treated animals vessels reoccluded in 6 of 7 animals (86%) at 33 +/- 6 min after reperfusion. With the lowest dose of acad esine (0.5 mg/kg/min) vessels reoccluded in 3 of 3 animals (100%) at 1 8 +/- 7 min. In animals treated with 1.0 mg/kg/min acadesine, the inci dence of reocclusion was reduced, but not significantly (p<0.1) to 2 o f 6 (33%), and time to reocclusion was prolonged to 59 +/- 11 min (p<0 .1). At the highest dose (2.0 mg/kg/min) of acadesine, only 2 of 8 (25 %) animals reoccluded (p<0.05), and time to occlusion was prolonged to 80 +/- 13 min (p<0.05). Acadesine had no effect on hemodynamics. Thes e results suggest that acadesine might prove beneficial in clinical se ttings of platelet activation and prothrombotic conditions, such as oc cur during thrombolysis with t-PA.