THE ROLE OF TUMOR-NECROSIS-FACTOR IN ENDOTOXIC-SHOCK

Tumor necrosis factor (TNF) has been implicated in hemodynamic changes of endotoxic shock. The temporal relationship of hypotension and TNF release in endotoxemia was studied. Carotid arteries of five intubated rats were cannulated and Escherichia coli 0127:B8 lipopolysaccharide (LPS) was infused over 10 seconds. Arterial blood pressure (ABP), hear t rate, and plasma TNF concentrations were measured at 0, 5, 15, 30, a nd 60 mins. Five to 15 mins after LPS, there was a marked decline in A BP (146 +/- 23 vs 57 +/- 5 mm Hg, p < 0.005), without a significant ri se in TNF. The heart rate did not change. From 15 to 60 mins, there wa s a rise in TNF concentrations (523 +/- 333 vs 5783 +/- 629 pg/ml, p < 0.005) while the same degree of hypotension persisted. It is conclude d that early hypotension after acute endotoxemia is not dependent on T NF alone. However, TNF may play a role in sustaining hypotension after endotoxemia.