Prostacyclin analogue, beraprost, sustains recanalization duration after thrombolytic therapy in acute myocardial infarction model.
Platelets play an important role in acute reocclusion after thrombolysis in acute myocardial infarction. We tested a new antiplatelet agent, the stable prostacyclin analogue, beraprost, in the prevention of reocclusion of reperfused vessels with a combination of recombinant tissue-type plasminogen activator (rt-PA) in a canine preparation of coronary artery thrombosis superimposed on high-grade stenosis. Intravenous infusion of rt-PA (17 micrograms/kg/min for 30 min) was combined with beraprost (100, 200 or 300 ng/kg/min for 60 min) or aspirin (35 mg/kg bolus i.v. before rt-PA infusion). The reperfusion time did not differ among the 4 groups. The time from reperfusion to reocclusion (one cycle) in the rt-PA plus beraprost 200 ng/kg/min group was significantly longer than the rt-PA alone group (40 +/- 8 min vs. 9 +/- 2 min, P < 0.05) and the recanalization duration calculated as the mean time from reperfusion to reocclusion in each cycle was prolonged in the rt-PA plus beraprost 200 ng/kg/min group compared with the rt-PA alone group (48 +/- 6 min vs 18 +/- 5 min, P < 0.05) and the reocclusion time and recanalisation duration tended to be elongated in the rt-PA plus beraprost 300 ng/kg/min group, whereas those were not altered by aspirin and 100 ng/kg/min of beraprost. Bleeding time was slightly prolonged and ex vivo platelet aggregation was slightly depressed by beraprost and aspirin. Systemic blood pressure was lowered with higher doses of beraprost. Beraprost sustained coronary reperfusion time and recanalization duration at the higher doses with an optimal level, but could not eliminate reocclusion completely.(ABSTRACT TRUNCATED AT 250 WORDS)
Saito
T
T
First Department of Internal Medicine, Fukushima Medical College, Japan.
Saitoh
S
S
Asakura
T
T
Kanke
M
M
Owada
K
K
Maruyama
Y
Y
D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D003328:Coronary Thrombosis / Q000150:complications / Q000188:drug therapy; D004285:Dogs; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000209:etiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012008:Recurrence; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D010975:Platelet Aggregation Inhibitors; C048081:beraprost; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator; D001241:Aspirin