Acadesine Reduces the Frequency of Coronary Artery Reocclusion Following rt-PA Induced Thrombolysis in the Dog

Summary

Acadesine is a ribose-substituted imidazole with antithrombotic properties mediated by adenosine. In view of the beneficial effects of antiplatelet agents on thrombolysis and post-thrombolytic reocclusion, we studied the effects of acadesine on t-PA induced coronary reperfusion and continued patency in anesthetized dogs with electrically-induced coronary 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 infusion of t-PA (10 μg/kg/min, i.v.). Acadesine had no effect on time 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 acadesine (0.5 mg/kg/min) vessels reoccluded in 3 of 3 animals (100%) at 18 ± 7 min. In animals treated with 1.0 mg/kg/min acadesine, the incidence of reocclusion was reduced, but not significantly (p<0.1) to 2 of 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. These results suggest that acadesine might prove beneficial in clinical settings of platelet activation and prothrombotic conditions, such as occur during thrombolysis with t-PA.

• References

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