[Thrombolysis of rabbit's pulmonary embolism with thrombus-targeted urokinase immune liposome].
OBJECTIVE
To develop thrombus-targeted urokinase immune liposome through incorporating D-dimer monoclonal antibody (DDmAb) to liposome and observe the thrombolytic efficiency in a rabbit pulmonary thromboembolism (PE) model.


METHODS
Reverse-phase evaporation method was used to develop targeted urokinase immune liposome by coupling DDmAb to urokinase liposome (liposomal-encapsulated urokinase) with glutaraldehyde. The PE models were induced by injecting 4 autologous emboli (2 mm x 5 mm) through jugular vein catheter into pulmonary arteries. New Zealand white rabbits (n = 32) were randomized into four groups: A group (TBS), B group (150 000 IU/kg UK), C group (30 000 IU/kg urokinase liposome) and D group (30 000 IU/kg urokinase immune liposome). The right ventricular pressure and the emboli size in pulmonary arteries were determined.


RESULTS
The right ventricular pressure increased significantly in PE rabbits (P < 0.01), the average value is (6.75 +/- 6.82) mm Hg (1 mm Hg = 0.133 kPa). Eighty minutes post various treatments, right ventricular pressure remained unchanged as post PE in group A [(40.15 +/- 11.22) mm Hg vs. (41.67 +/- 14.23) mm Hg], decreased to baseline level in group B and D [(34.71 +/- 8.67) mm Hg vs. (33.98 +/- 9.32) mm Hg, (30.65 +/- 6.67) mm Hg vs. (30.77 +/- 6.85) mm Hg, all P > 0.05], decreased but not returned to normal value in group C. Residual emboli size remained unchanged in group A and partly reduced in group C and more significantly reduced in group B and D. Hemorrhage of heart, kidney and liver was evidenced in group A but not in other groups.


CONCLUSIONS
Acute PE could be successfully treated by the thrombus-targeted urokinase immune liposome with D-dimer monoclonal antibody.
Lü
Cui-Ping
CP
Histology and Embryology Department of North China Coal Medical University, Tangshan 063000, China.
Yang
Hui
H
Wang
Jue
J
Dong
Xiao-Li
XL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001794:Blood Pressure; D004195:Disease Models, Animal; D005338:Fibrin Fibrinogen Degradation Products / Q000276:immunology*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008081:Liposomes; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000503:physiopathology; D011817:Rabbits; D015912:Thrombolytic Therapy / Q000379:methods*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage*
D000911:Antibodies, Monoclonal; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D008081:Liposomes; C036309:fibrin fragment D; D014568:Urokinase-Type Plasminogen Activator