The thrombolytic effect of miniplasmin in a canine model of femoral artery thrombosis.
OBJECTIVE
Miniplasmin was a des-kringle variant of plasminogen with potential pharmacological application. We investigated the thrombolytic effect of miniplasmin in a canine model of femoral artery thrombosis.


METHODS
In anesthetized dogs, a stable occlusive thrombus was formed by mechanical and electrolytic injury of the vessel wall, that the animals were later injected with miniplasmin (0.75 mg/kg, 1.5 mg/kg and 3.0 mg/kg, i.a.) and rt-PA (0.5 mg/kg, i.a.) intra-arterially. Hemodynamic parameters and hemorrhage status were monitored for 2 h. Thrombin time, activated partial thromboplastin time, prothrombin time and fibrinogen concentration were tested at 2 h after administration. Fibrin degradation product and D-dimer concentration were tested by ELISA.


RESULTS
The incidence of reperfusion in the miniplasmin (3.0 and 1.5 mg/kg) groups was 100%, and time to reperfusion was (3.3+/-1.0) and (7.0+/-2.3) min, which was shorter than rt-PA. After reperfusion, none of the vessels in the miniplasmin (1.5 and 3.0 mg/kg) groups reoccluded, whereas 20% of vessels reoccluded in the rt-PA group. Rudimental thrombus mass in the miniplasmin (1.5 and 3.0 mg/kg) groups were smaller than rt-PA. The operative wounds in all miniplasmin groups had no hemorrhage within 2 h. There were no significant differences in thrombin time, activated partial thromboplastin time and prothrombin time. Fibrinogen concentration in the miniplasmin (3.0 mg/kg) group reduced significantly as compared with baseline and thrombosis values, whereas these values in the miniplasmin (1.5 and 0.75 mg/kg) groups were unchanged. Fibrin degradation product and D-dimer concentration increased significantly after thrombolysis.


CONCLUSIONS
The results suggest that miniplasmin may be useful for the treatment of thrombosis and without complication of hemorrhage. This is in contrast to rt-PA, which intrinsically has a higher risk of occurring the hemorrhage risk.
Fu
Jieying
J
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, China.
Ren
Jianping
J
Zou
Libo
L
Bian
Guangxing
G
Li
Ruifu
R
Lu
Qiujun
Q
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001783:Blood Flow Velocity; D004195:Disease Models, Animal; D004285:Dogs; D005263:Femoral Artery / Q000503:physiopathology; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005341:Fibrinolysin / Q000494:pharmacology* / Q000502:physiology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology
D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D010446:Peptide Fragments; C036309:fibrin fragment D; C019493:miniplasmin; D005341:Fibrinolysin