Background: Complement activation occurs in patients with myocardial infarction treated with fibrinolytic agents and plays a critical role in reperfusion injury. This study was designed to determine whether pharmacologic activation of plasminogen directly induces complement activations.
Methods: Whole blood was incubated with plasminogen activators and the plasma was assayed for C3a levels as an indicator of complement activation.
Results: Therapeutic concentrations of tissue-type plasminogen activator, streptokinase, or urokinase increased C3a concentrations from a baseline of approximately 500 ng/ml to an average of 1300-1500 ng/ml with tissue-type plasminogen activator or urokinase, and to an average of approximately 4000 ng/ml with streptokinase (P < 0.01, versus baseline for all plasminogen activators). Plasminogen activation also enhanced complement activation induced by conventional complement activators.
Conclusions: These results indicate that pharmacologic plasminogen activation may exacerbate reperfusion injury either by directly inducing complement activation or by enhancing the activation initiated by other mechanisms, or both.