The effect of heparin on glomerular coagulation induced in mice by cycloheximide and bacterial lipopolysaccharide

The glomerular capillary coagulation in mice which follows challenge with cycloheximide and a submicrogram dose of endotoxin was shown to become fully established between 4 h and 6 h after challenge. Complete protection against the renal lesion was achieved by heparin treatment 4 h after challenge. The antifibrinolytic agent, tranexamic acid, given 4 h and 6 h after challenge, abolished this heparin-induced protection, but had no effect when given 6 h and 8 h after challenge. These findings suggest that heparin in some way delayed the onset of cycloheximide and endotoxin-induced irreversible coagulation in glomerular capillaries, and by so doing, allowed the development of local, protective, fibrinolytic activity. A relatively brief period of such fibrinolytic activity appeared to confer lasting protection against coagulation in glomerular capillaries. Appropriately timed treatment with hydrocortisone also abolished the heparin-initiated protection, and the evidence suggests that the steroid acts by inhibiting the development of local fibrinolytic activity.