ACTIVATION OF THE FIBRINOLYTIC SYSTEM DURING INTRACORONARY STREPTOKINASE ADMINISTRATION

Serial biochemical studies were performed in 12 patients treated with intracoronary streptokinase infusion for acute myocardial infarction, in order to study the method of activation of the fibrinolytic system during local administration of a relatively low dose of this drug and to determine correlations between systemic effects and reperfusion. Plasma samples were obtained before an every 15 minutes during the infusion of streptokinase and after completion of the therapy. Streptokinase dosage in this study was 211,000 .+-. 88,000 IU (.+-. SD). The average time from the onset of symptoms to the start of infusion was 2 hours 50 minutes (range 1 hour 10 minutes to 3 hours 30 minutes). Reperfusion occurred in six patients and temporary recanalization in three; in three patients no recanalization was achieved. Fibrinolytic assays of pretreatment plasma samples revealed elevated levels of plasminogen activators, presumably caused by the release of tissue-type plasminogen activator after a condition of stress. Plasminogen concentrations decreased from 94 .+-. 17% to 44 .+-. 30%. Alpha2-antiplasmin fell from 84 .+-. 27% to 12 .+-. 19%; in seven patietns no plasmin inhibitor activity was measurable at the completion of the infusion. Free plasmin occurred in samples only when this inhibitor had disappeared. This resulted in a lytic state leading to degradation of fibrinogen, the levels of which fell from 2.9 .+-. 0.7% to 1.5 .+-. 1.1%. Fibrinogen degradation products, measured in plasma with monoclonal antibodies, increased exponentially during streptokinase infusion in at least four patients. Despite the small number of study patients involved, systemic fibrinolysis, defined as fibrinogen decrease to below 2.0 g/liter, and recanalization appeared to be dependent on each other (chi-square = 7.1, p < 0.01). It may be inferred that systemic fibrinolysis after intracoronary administration of streptokinase promotes recanalization of occluded arteries, although this does not seem to be a prerequisite. It cannot be concluded from these data whether enhancement of intracoronary clot lysis by systemic effects is caused by free plasmin formed in the circulation or by endogenous thrombolysis made possible by the disappearance of the main inhibitor of fibrinolysis, alpha2-antiplasmin, or by the high local concentration of free streptokinase.