Systemic lysis protects against the effects of platelet activation during coronary thrombolysis.
Systemic lysis may protect against the platelet activation and ongoing thrombosis associated with coronary thrombolysis. To address this hypothesis, we compared urokinase and tissue-type plasminogen activator (t-PA) given intravenously in a chronic, canine model of coronary thrombosis. T-PA 10 micrograms/kg per min induced reperfusion in 55 +/- 7 min but complete reocclusion occurred in 9/10 animals. Reocclusion was prevented by combining t-PA with 7E3, an antibody to the platelet glycoprotein IIb/IIIa which abolished ex vivo platelet aggregation. A similar time to reperfusion was seen with urokinase 750-1,000 U/kg per min. In contrast to t-PA, complete reocclusion occurred in only 1/20 cases (P less than 0.001 vs. t-PA), despite evidence of continued platelet activation in vivo and platelet aggregation ex vivo. Furthermore, this did not reflect a difference in the clearance of the two plasminogen activators. However, plasma fibrinogen was undetectable after urokinase in contrast with t-PA. Furthermore, in animals treated with prourokinase 20 micrograms/kg per min, reocclusion (4/7) correlated with the degree of systemic lysis. To determine whether platelet activation modified the response to urokinase, it was combined with 7E3. 7E3 0.8 mg/kg reduced the time to reperfusion with t-PA (30 +/- 5, n = 6; P = 0.025), but not with urokinase (56 +/- 8 vs. 62 +/- 6, P = ns). Systemic lysis protects against the propensity of continued thrombosis during coronary thrombolysis to delay reperfusion and induce reocclusion. This may modify the requirement for adjunctive antiplatelet therapy.
Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee 37232.
D J
DJ
Fitzgerald
M
M
Hanson
G A
GA
FitzGerald
D000818:Animals; D003328:Coronary Thrombosis / Q000097:blood / Q000188:drug therapy*; D004285:Dogs; D005340:Fibrinogen / Q000032:analysis; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008297:Male; D015425:Myocardial Reperfusion; D015539:Platelet Activation; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D005343:Fibrinolytic Agents; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator