Comparison of the thrombolytic efficacy of defibrase and urokinase on canine coronary artery thrombosis and the mechanism of urokinase-induced hemorrhage.
The thrombolytic efficacy of defibrase (DF) and urokinase (UK) was evaluated and compared in a canine model in which left circumflex coronary artery (LCX) thrombus formation was initiated by electrical stimulation (150 UA, DC) of the arterial intimal surface via an implanted copper wire electrode. Forty-eight mongrel dogs were equally divided into 8 groups: six groups for both intravenous (iv) and intracoronary (ic) infusion of DF, UK and normal saline 30 min after complete obstruction by a LCX thrombus, the remaining two groups for iv infusion DF and UK 360 min after occlusion. Results showed that in the control groups no LCX recanalization after infusion occurred, but all the treated groups recanalized when drug infusion started 30 min after occlusion. Thrombus wet weight and infarct size were much higher in the control group. No significant differences were found between treated groups except that the recanalizing speed was fastest by ic UK with the highest occurrence rate of reperfusion arrhythmia. For 6-hour-old thrombi, DF was more effective than UK for recanalization. Thrombus wet weight and infarct size were lower in the recanalized dogs. Both agents reduced plasma plasminogen and fibrinogen significantly but serious incision bleeding was only found in the UK group. In order to study the mechanism underlying UK-induced hemorrhage, we observed the influences of UK and DF on blood coagulation factors in another 12 dogs. Results showed that DF only reduced factor 1 while UK additionally reduced coagulation factors 2, 7, 8 and 10, indicating that the non-selective depletive effect on coagulation factors may be one of the mechanisms of UK-induced hemorrhage. We conclude that both DF and UK can lyse fresh coronary thrombi, DF was more effective than UK on lysing older thrombi, considering its convenient use and less frequency of side effects, DF is therefore considered a more promising agent clinically.
D000818:Animals; D012103:Batroxobin / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy*; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D008297:Male; D012697:Serine Endopeptidases / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*
D012103:Batroxobin; D012697:Serine Endopeptidases; D014568:Urokinase-Type Plasminogen Activator