Effect of the thrombolytic agent, streptokinase, on the responses to endotoxemia in conscious rats.
The potential role of coagulation defects as a pathologic mediator in septic shock is well documented, especially as it relates to increased thromboxane formation, thrombocytopenia, and disseminated intravascular coagulation. The present study was designed to determine the effect of the thrombolytic agent streptokinase on the sequelae of endotoxemia in the rat. Conscious male Sprague-Dawley rats were given a bolus intravenous dose of Salmonella enteritidis endotoxin (20 mg/kg; LD90 dose) 5 min after the intravenous administration of streptokinase (10,000 U/kg bolus + 1,000 U/kg/hr infusion), or heparin (100 U/kg bolus + 30 U/kg/hr infusion). The effects of streptokinase or heparin on blood clotting were determined by measuring ex vivo clot formation 1 hr after the administration of endotoxin. In naive and endotoxemic animals, both agents significantly reduced clot formation (P less than 0.05). In endotoxemic animals, streptokinase or heparin improved survival to 70%, compared to 8% survival in the endotoxin + vehicle group (P less than 0.05). The improvement in survival with streptokinase was dose-dependent. Neither streptokinase nor heparin prevented the thrombocytopenia or hemoconcentration which developed in endotoxemic animals. These results demonstrate the potential utility of streptokinase for improving survival in endotoxemia and further confirm the deleterious contribution of coagulation disorders in endotoxic mortality.
Smith
E F
EF
Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, Pennsylvania 19406.
Kinter
L B
LB
Jugus
M
M
Zeid
R
R
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D004353:Drug Evaluation, Preclinical; D004731:Endotoxins; D006339:Heart Rate / Q000187:drug effects; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012477:Salmonella enteritidis; D012772:Shock, Septic / Q000139:chemically induced / Q000150:complications* / Q000401:mortality; D013300:Streptokinase / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000517:prevention & control*; D013927:Thrombosis / Q000517:prevention & control*
D004731:Endotoxins; D006493:Heparin; D013300:Streptokinase