Changes in Levels of Plasma Pre-Kallikrein, Kallikrein and Kallikrein Inhibitors During Endotoxin Shock in Dogs

Plasma protease activity is known to be increased during endotoxin shock and recent studies have indicated that the plasma kallikrein-kinin system becomes activated by circulating endotoxin. Plasma levels of pre-kallikrein kallikrein and kallikrein inhibitors were therefore determined in samples from dogs infused with E. coli endotoxin, using assays with a chromogenic substrate for plasma kallikrein(Chromozyme -PK, Pentapharm, Basle, Switzerland). “Fast-reacting” and “time-dependent” inhibitors of kallikrein were studied using purified human plasma kallikrein. Considerably reduced levels of plasma pre-kallikreiri and increased levels of kallikrein were detected in the late phase of shock and significant reductions in “fast-reacting” and “time-dependent” inhibition of kallikrein was observed. These results show that during endotoxin shock plasma pre-kallikrein becomes activated to kallikrein and indicate that kallikrein inhibitors play an important mediatory role in the pathophysiology of endotoxin shock.