Summary
Rabbits treated for 4 days with cortisone to prepare for the generalized Shwartzman
reaction (GSR) were infused with thrombin or endotoxin. Whereas endotoxin induced
the GSR, infusion of from 120-400 U/kg of thrombin over 1 to 2½ hr failed to induce
the GSR. Mean values for fibrinogen consumption after thrombin or endotoxin, calculated
from changes in plasma fibrinogen concentration and plasma 12 5I-fibrinogen radioactivity, were as follows: for rabbits infused with thrombin, from
43 to 61 mg/kg over a 3 hr period; for rabbits infused with endotoxin, 58.5 mg/kg
over a 6 hr period. A small peak of non-clottable protein radioactivity, indicative
of secondary fibrinolysis, was found in animals infused with thrombin but not in animals
infused with endotoxin. A striking late rise in plasma fibrinogen levels was noted
in animals infused with endotoxin. It was not noted in animals infused with thrombin.
This observation provides further evidence that endotoxin stimulates fibrinogen synthesis
by mechanisms independent of intravascular clotting or fibrinolysis. The failure to
produce the GSR with thrombin in cortisone-treated rabbits leads us to conclude that
depression of reticuloendothelial cell clearance of fibrin can not account for the
preparatory effect of cortisone for the GSR after endotoxin.
