Thrombolysis with intracoronary administration of YM866, a novel modified tissue-type plasminogen activator, in a canine model of coronary artery thrombosis.
We compared the thrombolytic activity of YM866, a novel modified tissue-type plasminogen activator, with that of t-PA by intracoronary administration in a canine thrombosis model of copper coil-induced 6-hr-old thrombi. Either drug was administered by a single injection (10 min) or multiple injection (4 x 10 min) under heparinization (300 IU/kg, i.v.). The reperfusion rate of YM866 was 4 times higher than that of t-PA when administered by single injection. Time to reperfusion of YM866 by single injection was shorter than that of either agent by multiple injection. No group showed any decrease in plasma fibrinogen levels. No acute reocclusion was seen in animals with YM866 by single injection. The improved thrombolytic activity of YM866 by single injection correlated with the relatively higher antigen levels of this agent due to its prolonged biological half-life. These results suggest that single intracoronary administration of YM866 is a safe and effective thrombolytic method for rapid recanalization and lowered acute reocclusion without activation of systemic fibrinolysis.
Kawasaki
T
T
Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Katoh
M
M
Kaku
S
S
Gushima
H
H
Takenaka
T
T
Yui
Y
Y
Kawai
C
C
D000818:Animals; D003328:Coronary Thrombosis / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D007275:Injections, Intravenous; D008297:Male; D010958:Plasminogen / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D000979:alpha-2-Antiplasmin / Q000032:analysis
D011994:Recombinant Proteins; D000979:alpha-2-Antiplasmin; D005340:Fibrinogen; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; C085027:pamiteplase