Plasma tumor necrosis factor and post-traumatic hyperdynamic sepsis evoked by endotoxin

To examine the role of systemic plasma tumor necrosis factor (TNF) in the septic response following trauma, an endotoxin (lipopolysaccharide (LPS)) challenge was administered to anesthetized mongrel pigs 72 h following either hemorrhagic shock/resuscitation or sham shock. For TNF to be considered a mediator, at least two conditions should be satisfied: a TNF increase should precede other manifestations of the septic response and the magnitude of that increase should correlate with the symptoms. Immediately following resuscitation from shock, hemodynamics were stable, but heart rate, cardiac index (Cl), and systemic oxygen delivery (DO₂) were elevated 20-60%, and systemic vascular resistance (SVR) was decreased 40%, relative to the preshock baseline. After 72 h, the animals were reanesthetized, reinstrumented, and all he-modynamic values were near normal in both groups. At this point, either 1.5 (shock, n = 2; sham, n = 2), 15 (shock, n = 7; sham, n = 6) or 150 (shock, n = 11; sham, n = 4) µg/kg of Escherichia coli LPS was administered intravenously over 30 min. Serial hemodynamic data, complete blood counts, and TNF were recorded for 3 h post-LPS. LPS evoked profound leukopenia and pulmonary hypertension within 15 min that was followed by a hyperdynamic septic response (i.e., progressive arterial desaturation, tachypnea, tachycardia, increased Cl, and decreased SVR) and rise in plasma TNF at 60-90 min. In the shock group, LPS-evoked TNF changes were less than or equal to those in the sham group, even though mortality was higher after shock. By 60 min after 15 µg/kg LPS, plasma TNF was 10 ± 2 vs. 21 ± 4 units/ml in shock vs. sham (p < .05). The corresponding mortality after 3 h was 2/7 in shock and 0/6 in sham. After 150 µg/kg LPS, plasma TNF increased to 16-18 units/ml in both groups, but the 3 h mortality was 8/11 in shock and 1/4 in sham. Since plasma TNF did not rise until after other symptoms of an LPS-evoked inflammatory response were already apparent and since the increment in plasma TNF was not potentiated by a prior bout of resuscitated shock, it is unlikely that the response evoked by a septic challenge following traumatic shock can be directly attributed to excessive levels of systemic TNF.