HUMAN FIBRINOLYSIN WITH AND WITHOUT UROKINASE: ITS EFFECT ON EXPERIMENTAL ARTERIAL THROMBI IN DOGS

Abstract

The lytic effects of heat-treated, sterile solutions of spontaneously activated and urokinase-activated fibrinolysin on occlusive experimental arterial clots have been studied. For this purpose methods for the preparation of urokinase and activation of profibrinolysin, the production of traumatic arterial thrombi in dogs, and the recording of clot lysis are described. Single injection as a means of administration was compared with the traditional method of infusion. When used in conjunction with a prompt assay of the in vivo fibrinolytic activity, which was developed for this purpose, the injection method was preferred. The results indicated that spontaneous fibrinolysin, given by single injection, was as effective in lysing clots as were preparations of fibrinolysin that contained activator. The approximate therapeutic dose for both types of fibrinolysin under the conditions described was found to be 225–325 Michigan Department of Health caseinolytic units per kg body weight. Lysis of occluding arterial thrombi was achieved within a few hours after administration of fibrinolysin by injection, and arteries remained patent during the week of posttreatment observation. No toxic effects due to the fibrinolysin or the glycerol present as stabilizer could be demonstrated after the therapeutic dose. The only undesirable side effect of overdose of fibrinolysin was a transient incoagulability of the blood.