Twelve patients (age 33-77 years, mean age 68.4 years) with peripheral vascular disease (PVD) stage III-IV received continuous intravenous infusions of 5 ng prostacyclin (PGI2)/kg/min and physiological saline for 7 days. The administration was randomized and double-blind with an interval of 7 days between the infusions. During PGI2 infusion systolic blood pressure fell significantly from 147.8 +/- 4.8 mm Hg to 140.6 +/- 4.0 mm Hg (P less than 0.01) and returned to 144.5 +/- 4.9 mm Hg post infusion. Transcutaneous pO2 (tcpO2) measured on the instep of the affected limb increased significantly by 8.9 +/- 3.8 Torr during PGI2 infusion and remained elevated during the subsequent week. A significant reduction of pain was observed from the 5th day of PGI2 infusion, lasting for at least the following observation period. Platelet cAMP increased from 18.8 +/- 1.5 pmol/10(8) platelets to 24.7 +/- 1.6 pmol/10(8) platelets on the 3rd day of PGI2 infusion (P less than 0.01). Spontaneous platelet aggregation was also significantly reduced during PGI2 infusion. However, 7 days after the infusion thromboxane B2 (TXB2) in plasma and spontaneous platelet aggregation significantly increased in comparison with the preinfusion values, indicating a rebound phenomenon. The clinical outcome was favorable in 9 of 12 patients, was unchanged in two patients, while progressing to limb amputation in one patient.
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.
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.
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