Soluble tumor necrosis factor receptor prevents post-pump syndrome

Post-pump syndrome is an acute lung injury following cardiopulmonary bypass (CPB) which is indistinguishable from the adult respiratory distress syndr ome (ARDS), Tumor necrosis factor (TNF) is central to the inflammatory proc ess and is capable of triggering the entire pathophysiologic response leadi ng to ARDS. We hypothesized that treatment with a soluble TNF receptor-bind ing protein (TNFbp) would reduce the increase in serum TNF and prevent acut e lung injury in our sequential insult model of ARDS following CPB, Anesthe tized pigs were randomized to one of three groups: Control (n = 3), surgica l preparation only; CPB + LPS (n = 6), femoral-femoral hypothermic bypass f or 1 h followed by infusion of low dose Escherichia coli lipopolysaccharide (LPS; 1 mu g/kg); and TNFbp + CPB + LPS (n = 4), pretreatment with intrave nous TNFbp (2 mg/kg) followed immediately by both insults. CPB + LPS caused severe lung injury demonstrated by a significant fall in PaO2 and an incre ase in both intrapulmonary shunt and peak airway pressure as compared to al l groups (P < 0.05), These changes were associated with a significant incre ase in plasma TNF level and pulmonary neutrophil sequestration. TNFbp signi ficantly reduced plasma levels of TNF and prevented the lung injury typical ly observed with this ARDS model, but did not reduce pulmonary neutrophil s equestration. Thus, elevated serum TNF is not responsible for neutrophil se questration but does play a role in neutrophil activation which causes lung injury. Prophylactic use of TNFbp in CPB patients may prevent neutrophil a ctivation and reduce the incidence of post-pump ARDS. (C) 1999 Academic Pre ss.