Generation of fibrinolytic activity by infusion of activated protein C into dogs

Abstract

Bovine-activated protein C, administered intravenously to dogs, increased the rate of lysis of whole blood clots. Protein C, bovine prothrombin, and diisopropylfluorophosphate-inactivated protein C(a) do not increase the rate of lysis. Repeated infusions of protein C(a) sustain rapid blood clot lysis, but neither elevate circulating fibrin-split products nor decrease circulating plasminogen levels. The administration of protein C(a) results in the elevation of the levels of lysine-absorbable plasminogen activator activity in the plasma. When partially purified concentrates of this activator are added to normal dog blood at the levels seen following protein C(a) injection, the rate of blood clot lysis is similar to that seen after protein C(a) injection. The addition of protein C(a) to citrated whole blood in vitro, with the subsequent neutralization of protein C(a) with antibodies, results in increased rates of lysis when plasma made from the treated blood is reinjected into the animal. The generation of fibrinolytic activity is dependent on both cellular and plasma components of blood. A model of protein C(a) fibrinolytic activity has a minimum of two components: a secondary messenger formed by protein C(a) action on blood cells and plasma, and the subsequent appearance of plasminogen activator in the animal in response to that messenger.