The thrombolytic effect of miniplasmin in a canine model of femoral artery thrombosis.

Abstract

BACKGROUND AND PURPOSE:

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.

• Authors: Jieying Fu, Jianping Ren, Libo Zou, Guangxing Bian, Ruifu Li, Qiujun Lu
• Journal: Thrombosis research (Thromb Res) Vol. 122 Issue 5 Pg. 683-90 ( 2008) ISSN: 0049-3848 [Print] United States
• PMID: 18328540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fibrin Fibrinogen Degradation Products
• Fibrinolytic Agents
• Peptide Fragments
• fibrin fragment D
• miniplasmin
• Fibrinolysin

Topics

• Animals
• Blood Coagulation (drug effects)
• Blood Flow Velocity
• Disease Models, Animal
• Dogs
• Femoral Artery (physiopathology)
• Fibrin Fibrinogen Degradation Products (metabolism)
• Fibrinolysin (pharmacology, physiology)
• Fibrinolytic Agents (pharmacology)
• Male
• Peptide Fragments (pharmacology, physiology)
• Thrombolytic Therapy (methods)
• Thrombosis (blood, drug therapy, physiopathology)