Prostacyclin analogue iloprost decreases thrombolytic potential of tissue-type plasminogen activator in canine coronary thrombosis.
Platelets play an important role in the formation of a coronary thrombus and reocclusion after thrombolysis. Therefore, we examined the thrombolytic potential of concomitant intravenous administration of potent platelet inhibitor iloprost, a prostacyclin analogue, with tissue-type plasminogen activator (t-PA; n = 8) and t-PA alone (n = 9) in dogs with an electrically induced occlusive coronary artery thrombus. t-PA (0.75 mg/kg) was given over 20 minutes, and iloprost (4 micrograms/kg) was given over 40 minutes. Reperfusion rate was 63% (five of eight dogs) in the t-PA plus iloprost group and 67% (six of nine dogs) in the t-PA alone group (p = NS). The time to thrombolysis (or reperfusion) in the t-PA plus iloprost group was almost twice as great as in the t-PA alone group (33.0 +/- 13.3 vs. 18.5 +/- 6.7 minutes, mean +/- SD, p less than 0.02), and the duration of reperfusion was much shorter (3.4 +/- 1.8 vs. 39.3 +/- 17.4 minutes, p less than 0.005). Peak coronary artery blood flow after reperfusion in the t-PA plus iloprost group was also less (20 +/- 17 ml/min) than in the t-PA alone group (58 +/- 21 ml/min, p less than 0.005). Reocclusion occurred in all dogs given t-PA with iloprost despite potent synergistic platelet inhibitory effects of t-PA and iloprost, whereas four of six dogs given t-PA alone reoccluded. Neither regimen exerted a significant beneficial effect on regional myocardial shortening during coronary reperfusion. Plasma levels of t-PA were lower when iloprost was given with t-PA (1,022 +/- 360 vs. 1,459 +/- 270 ng/ml in t-PA alone group, p less than 0.05). The detrimental effects of iloprost identified in this study may relate to the reduction in plasma t-PA concentrations by its degradation in the liver caused by the prostacyclin analogue iloprost.
Department of Medicine, University of Florida College of Medicine, Gainesville 32610.
F A
FA
Nicolini
J L
JL
Mehta
W W
WW
Nichols
T G
TG
Saldeen
M
M
Grant
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy*; D003328:Coronary Thrombosis / Q000188:drug therapy*; D004285:Dogs; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000627:therapeutic use*; D016285:Iloprost; D008297:Male; D015425:Myocardial Reperfusion; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012008:Recurrence; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D010975:Platelet Aggregation Inhibitors; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator; D016285:Iloprost