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

Bovine-activated protein C, administered intravenously to dogs, increases the rate of lysis of whole blood clots. Protein C, bovine prothrombin, and diisopropylfluorophosphate-inactivated protein Ca do not increase the rate of lysis. Repeated infusions of protein Ca sustain rapid blood clot lysis, but neither elevate circulating fibrin-split products nor decrease circulating plasminogen levels. The administration of protein Ca results in the elevation of the levels of lysine-adsorbable 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 Ca injection, the rate of clot lysis is similar to that seen after protein Ca injection. The addition of protein Ca to citrated whole blood in vitro, with the subsequent neutralization of protein Ca 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 Ca fibrinolytic activity has a minimum of two components: a secondary messenger formed by protein Ca action on blood cells and plasma, and the subsequent appearance of plasminogen activator in the animal in response to that messenger.