Pretreatment with a blocking monoclonal antibody to P-selectin accelerates pharmacological thrombolysis in a primate model of arterial thrombosis.
It has been established that the fibrin content of a developing thrombus can be dramatically reduced with the use of the GA6 monoclonal antibody, which is directed against P-selectin (CD62p). This effect is probably related to diminished tissue factor activity on monocytes in the presence of P-selectin antagonism. Therefore, we hypothesized that an occlusive arterial thrombus formed in the presence of a P-selectin monoclonal antibody would be more susceptible to lysis with standard thrombolytic therapy. To test this hypothesis, 22 male cynomolgus monkeys were anesthetized and instrumented for induction of thrombosis of a femoral artery. Endothelial injury was induced by passing a 150-microA anodal current through a small electrode that was placed in the femoral artery. Blood flow through the artery was continuously monitored using an ultrasonic transit-time flowmeter. The GA6 monoclonal antibody (1 mg/kg) or control, isotype matched mouse IgG1 (P23 or P7) was administered i.v. 1 hr before electrolytic endothelial injury. In the P23 group (n = 11), an occlusive thrombus formed in 52.1 +/- 8.5 min, and in the GA6 group (n = 11), an occlusive thrombus formed in an average time of 52.0 +/- 8.1 min. After formation of an occlusive thrombus, the current was terminated and intravenous heparin (100 U/kg + 50 U/kg/hr) was administered to prevent clot extension.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006439:Hemodynamics; D006493:Heparin / Q000627:therapeutic use; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D019007:P-Selectin / Q000378:metabolism*; D013300:Streptokinase / Q000627:therapeutic use; D013927:Thrombosis / Q000188:drug therapy / Q000503:physiopathology*
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; C105957:GA6 monoclonal antibody; D019007:P-Selectin; D005340:Fibrinogen; D006493:Heparin; D013300:Streptokinase