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Ten patients with 13 stenoses in the pelvic area were treated with low doses of streptokinase (30 000 U/h) for 72 hours. A significant improvement in the degree of stenosis was obtained as shown by post-stenotic pressure values. Biochemically there was a marked plasminaemia with moderately low fibrinogen levels. Streptokinase treatment with low doses could form an alternative method of treatment in arterial stenoses.

Streptokinase was dissolved in various solvents and the decay recorded. The method employed was a recently described clot lysis assay for quantitative streptokinase determination. The decrease in activity of 5 u streptokinase, 1500 u streptokinase, and 50,000 u steptokinase dissolved in one milliltre of different solvents (NaCl solution, glucose solution, laevulose solution, dextran solution (Rheomacrodex), gelatin solution (Haemaccel, starch solution (Plasmasteril,albumin solution, Michaelis buffer, heparin-glucose solution) and incubated over various periods of time (15 min, 30 min, 45 min, 60 min, 4h, 8h, 12h, 48h) was investigated. Solution media tested for streptokinase-potecting quality were broken down into three groups.-Group I: Solvents displaying excellent stabilizing properties (gelatin, albumin).-Group II: Solvents displaying medium stabilizing properties (dextran, levulose)--Group III: Solvents displaying properties (starch, NaCl, glucose, Michaelis buffer).--In testing streptokinase concentrations as used for therapeutic purpose (1500 u/ml, 50,000 u/ml), no decay was found to take place over observation periods as long as 48 h. This finding was independent of the different solvents (Group I, II or III) employed. Heparin stored with streptokinase at rooom temperature did not alter the streptokinase stability. From the clinical point of view, the choice of solvents for streptokinase infusion turned out to be of minor importance.

Two-day treatment with activator (equimolar streptokinase-human plasminogen complex) was given to 26 patients. Indications were chronic arterial occlusion and stenosis of the lower-limb arteries (25 patients), and thrombosis of the subclavian veins. The onset of claudication had on average been 7.5 months previously, average walking distance 288 metres. Five occlusions of iliac arteries and three of femoral arteries were removed. In addition, stenosis of the aorta (one case), the iliac artery (ten cases) and femoral artery (one case) was partly removed. Occlusion of the axillary vein was also removed. Average duration of the successfully treated occlusions was 4.3 months. Those stenoses that responded to activator had the well-known morphological criteria for fibrinolysis. The walking distance of the patients increased from an average of 288 to 401 metres. Activator treatment was well tolerated. No serious, especially cerebral, complications occurred. The most striking laboratory finding was of circulating plasmin during the entire duration of the infusion.

144 patients were treated with 50.000 or 100.000 fibrinolytic units (U) activator per hour over a period of up to 5 days. The drug is not yet available but in trial for the time being. We report on a survey of laboratory results in 32 of these patients. The plasminogen content of 100.000 U activator is comparable to the plasminogen content of 29 ml plasma. During activator infusion laboratory findings showed a moderate fall in plasminogen and fibrinogen. Plasmin activity was measurable during the whole period of treatment while antiplasmin was lowered considerably. There was a distinct hypocoagulabilty during activator infusion visible by a prolongation of the thrombin time and aPTT. Interestingly, no measurable activator or streptokinase activities appeared in the plasma during activator infusion. This is in contrast to findings with conventional streptokinase infusion schemes.

Ten patients with 13 stenoses in the pelvic area were treated with low doses of streptokinase (30 000 U/h) for 72 hours. A significant improvement in the degree of stenosis was obtained as shown by post-stenotic pressure values. Biochemically there was a marked plasminaemia with moderately low fibrinogen levels. Streptokinase treatment with low doses could form an alternative method of treatment in arterial stenoses.

A method of a quantitative determination of plasma streptokinase concentrations in patients undergoing streptokinase infusion is described. The principle of this method is based on the clot lysis time recorded by the thromboelastograph. The test clot constituents were bovine fibrin, bovine plasminogen, human euglobulin, EDTA, human plasma (of unknown streptokinase quantity) and thrombin. As rather high concentrations (fixed excess) of plasminogen (euglobulin) and fibrinogen were present in the test coagulum, no interference with changing plasminogen and fibrinogen levels of the patient's plasma was observed. Furthermore, due to high EDTA concentrations, no interaction with platelet functions and coagulation factors took place. The standard deviation in measuring 2 u streptokinase in 1 ml human plasma was determined as s = +/- 0.19 u/ml, of 5 u streptokinase at s = +/- 0.47 u/ml and of 20 u streptokinase at s = +/- 2.5 u in 1 ml of human plasma. Plasma samples of patients undergoing fibrinolytic treatment were investigated with regard to their streptokinase content. Streptokinase concentration values varied between 0.7 u and 15 u/ml plasma. The average half life of streptokinase in the organism was 18 min. The decay of streptokinase in plasma at different temperatures and over various periods of time was also determined. A considerable loss of streptokinase in the plasma during storage at room temperature could be observed. Therefore, the determination procedures should be carried out without delay.

435 arterial occlusions were treated with streptokinase over a period of 3 days. A continuous streptokinase regimen with a maintenance dose of 100 000 u SK/h was administered. The successful removal of femoral obstructions was possible in 8.9%. A complete dissolution of the iliac thrombus masses had been achieved in 19%. 41 aortic occlusions were treated. The treatment was capable of removing the aortic obstructions in 24%. It became evident that there was a close relationship between the average occlusion time and the respective clearance rate. Por example, in patients undergoing lysis treatment during the very first two weeks after femoral occlusion, clearance was established in 75% and best lytic results were achieved if the history of iliac occlusion was well below 3 months duration. The relationship of vessel clearance rate and walking distance showed, that on the average there was no lengthening in walking distance where treatment had failed (no vessel clearance obtained). On the other hand, a significant average rise in walking distance from initially 325 up to 800 meters (p < 0.05) was seen when vessels clearance had been recorded.