Experimental disseminated intravascular coagulation (DIC)

Abstract

Endotoxinemia was produced in six Japanese monkeys (7-13kg) by two suitably spaced (24hrs, Fig. 1, Experiment I) and by a continuous (8hrs, Fig. 1, Experiment II) intravascular injection with endotoxin (ET) from E. coli. The changes of concentration of ET in plasma, and faculties of coagulative, fibrinolytic, kinin forming and complement systems were investigated before and after treatment with ET. Body temperature, arterial pressure, pH, pO2, pCO2, Ht and Hb in blood were checked throughout the experiment.The main observations were as follows.[1] Two spaced injection of ET (0.3-2mg/kg, 3 monkeys)Et in plasma rose to 0.1-1μg/ml of plasma immediately after the injection of ET and thereafter decreased gradually (Fig. 1, Experiment I). Activation of coagulation system was suggested by 60 to 70% decrease in platelet count and 20 to 30% prolongation of APTT and PT except for TT. Intrinsic coagulation factors, F. XII, F. XI, F. IX, F. VIII and extrinsic factor, F. VII decreased 20 to 30% after the treatment of first ET (ET-1), and further decreased 40 to 60% after second ET (ET-2). However, fibrinogen increased about two times before the treatment. Activation of fibrinolytic and kinin forming systems was indicated by the decrease of plasminogen and prekallikrein, generation of plasmin, kallikrein and FDP after ET-2 (Fig. 2). Complement factors, C3proactivator, C3c and C4 were decreased after ET-1 and ET-2.[2] Continuous injection of ET (1-5mg/kg/hr, 3 monkeys)ET in plasma rose 1-10μg/ml of plasma immediately after the first injection of ET and maintained its concentration to the death (Fig. 1, Experiment II). Activation of coagulation system was suggested by the extreme decrease in platelet count, prolongation of APTT, PT and TT. The decreases of F. XII, F. X and F. II were observed at 3hrs after the treatment of first ET. The decreases of F. IX, F. VIII and F. V were observed at 6hrs, and F. VII and fibrinogen decreased at 9hrs (Table 1). These findings indicate that ET activates the intrinsic coagualtion system. Activation of fibrinolytic and kinin forming systems was observed markedly as compared as the experiment of two spaced injection of ET (Fig. 3). In complement system, alternative pathway was activated. In plasma inhibitors, antithrombin III decreased, but α2-macroglobulin, C1s inhibitor and α2-plasmin inhibitor slightly decreased.These results in Japanese monkeys treated with ET have led us to conclude that DIC produced with ET may have been occured initially by the activation of intrinsic coagulation factor, F. XII, accompanying by the activation of prekallikrein and plasminogen.