Failure of prostacyclin analog iloprost to sustain coronary blood flow after recombinant tissue-type plasminogen-induced thrombolysis in dogs.
The coronary artery often reoccludes soon after the flow has been restored with recombinant tissue-type plasminogen activator (TPA) in dogs with electrically-induced thrombosis. The coronary artery reocclusion relates to intense in situ platelet activation and thrombin generation in the reperfused coronary artery. To determine the effect of a potent platelet inhibitor, the prostacyclin analog iloprost, in the prevention of coronary artery reocclusion, an occlusive thrombus was created in the left anterior descending coronary artery in 23 dogs. Coronary artery reflow occurred in 17 dogs after TPA (1 mg/kg over 20 minutes intravenously) administration. After the reflow was established, 10 dogs were given saline and 7 dogs were given iloprost (4 micrograms/kg over 40 minutes). In the saline-treated group, the coronary artery reoccluded in 8 of 10 dogs over 90 minutes (reocclusion rate 80%). In the iloprost-treated group, the coronary artery reoccluded in five of seven dogs (reocclusion rate 71%; p = NS vs TPA alone). The magnitude of peak coronary blood flow and duration of flow were similar in dogs given saline or iloprost after TPA-induced thrombolysis. Scanning electron microscopy showed residual thrombus and the appearance of coronary arterial narrowing distal to the thrombus in all dogs examined. Thus residual thrombus formation and coronary artery narrowing continue to occur after TPA-induced thrombolysis in dogs whether the animals are treated with saline or iloprost. Administration of iloprost after reflow does not modulate the frequency of coronary artery reocclusion.
Nichols
W W
WW
Department of Medicine, University of Florida College of Medicine, Gainesville.
Nicolini
F A
FA
Khan
S
S
Saldeen
T G
TG
Mehta
J L
JL
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D003331:Coronary Vessels / Q000473:pathology; D004285:Dogs; D005260:Female; D016285:Iloprost / Q000627:therapeutic use*; D008297:Male; D008855:Microscopy, Electron, Scanning; D012008:Recurrence; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D010959:Tissue Plasminogen Activator; D016285:Iloprost