Acadesine reduces the frequency of coronary artery reocclusion following rt-PA induced thrombolysis in the dog.
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 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 reperfusion, and incidence and time to reocclusion following infusion of t-PA (10 micrograms/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 or 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.
Young
M A
MA
Department of Cardiovascular Pharmacology, Gensia, Inc., San Diego, CA 92121, USA.
Henry
C
C
Wong
S
S
Bullough
D
D
Mullane
K
K
D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D003327:Coronary Disease / Q000517:prevention & control*; D004285:Dogs; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D008297:Male; D010477:Perfusion; D011994:Recombinant Proteins / Q000008:administration & dosage; D012263:Ribonucleosides / Q000008:administration & dosage*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine; D010959:Tissue Plasminogen Activator