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.
