The Lysis in Rabbits of Intravascular Blood Clots by the Streptococcal Fibrinolytic System (Streptokinase)

Abstract

1. Based upon quantitative estimations of the factors that promote or retard the development and activity of the streptococcal fibrinolytic phenomenon, an active lytic system was developed within the circulating blood stream of rabbits following the intravenous infusion of streptokinase. During the infusion of adequate doses of SK, an active lytic system was observed to be present within 30 minutes following the beginning of the experiment and remained present for periods of time ranging from 1 to 20 hours depending primarily upon the concentration of SK and the duration of the infusion. Some of the biochemical changes accompanying the lytic system in vivo were: (a) a striking fall in the plasminogen; (b) a moderate fall in the serum inhibitor and the fibrinogen; and, (c) a rise in the acid-soluble nitrogen. These changes were usually self-terminating within 24 hours following the infusion of SK. In earlier studies similar trends were observed in the chest fluid of patients with hemothorax and empyema treated locally with streptokinase (22). 2. Intravascular clots, induced artificially by local applications of sodium morrhuate within the ear vein of the rabbits, were observed to liquefy and disappear in 23 of 25 rabbits during the intravenous infusion of SK into the opposite ear. The average quantity of SK necessary to effect an active lytic system was found to be about 40,000 units per kilo per hour. The clot in the ear vein was observed to be lysed completely in periods of time ranging from 3 to 7 hours after the infusion of SK was begun. Maintenance of an active lytic system for 3 to 4 additional hours was required to prevent re-formation of the clots at the original site. In 3 of 4 rabbits in which clots did reform, ACTH had been given to combat the toxic effects of the streptococcal concentrates. 3. The toxicity of the unusually large dose of the streptococcal concentrates, containing measured amounts of SK, along with other identifiable and unknown substances, was considerable, inasmuch as 8 animals eventually died. No evidence of pulmonary infarction was observed at autopsy. The administration of ACTH appeared to prevent a fatal outcome in at least 3 of the rabbits. Further studies of toxicity are in progress.

A Discussion of the Role of Complex Evolved Systems in the Development of Invasive Cardiovascular Interventions as Illustrated by the Blalock- Taussig Shunt and Intra-Arterial Stents

“…The direct injection using less streptokinase proved efficacious in addition to limiting the side effects [231]. Streptokinase is a product of the metabolism of hemolytic streptococcus and was first proposed as a clot buster in the early 1950s [232][233][234][235]. Experiments on animals revealed varying effectiveness due to species variability [236].…”

Intravenous Thrombolytics for Ischemic Stroke

“…In the late 1940s, streptokinase was used therapeutically to treat bloody conditions, such as pleural exudates and hemothorax. Although Johnson and Tillet [10] were able to successfully lyse clots (in a rabbit model) using streptokinase, Fletcher et al [11] were the first to deliver IV streptokinase to human patients suffering from acute myocardial infarction (AMI) in 1958.…”

Studies on the Pathogenesis of Acute Inflammation

“…Crystalline soybean trypsin inhibitor (SBI) was added to all blood samples according to the method of Johnson and Tillett to prevent destruction of fibrinogen in vitro (10). It may be seen in Fig.…”