Hepatic TNF production following gramnegative bacteremia or hypovolemic shock predisposes to acute lung injury. However, TNF expression may be modified by the manner in which the hepatic O2 supply is reduced and equal...Hepatic TNF production following gramnegative bacteremia or hypovolemic shock predisposes to acute lung injury. However, TNF expression may be modified by the manner in which the hepatic O2 supply is reduced and equally important, its timing relative to bacteremia. Brief secondary hypoxic stress of bufferperfused rat livers downregulates E. Coli (EC)induced TNF expression whereas lowflow ischemia preceding EC increases subsequent TNF production owing to reactive O2 species (ROS). Here we determined whether 30 min of constantflow hypoxia preceding 109 intraportal EC likewise increases antigenic and bioactive TNF protein concentrations during reoxygenation via production of ROS. Multiple groups (n=38) were studied over 180 minutes, circulation antigenic TNF decreased in H/R+EC vs. EC controls (1 939640 vs. 12 4072 476 g/L at t=180 min; P<001, along with TNF bioactivity). TNF protein were not restored to control levels in ALLO+H/R+EC. Thus, ECinduced hepatic TNF production and export is strongly O2dependent in intact liver regardless of the generation of ROS or the sequence of bacteremia and modest hypoxic stress.展开更多
文摘Hepatic TNF production following gramnegative bacteremia or hypovolemic shock predisposes to acute lung injury. However, TNF expression may be modified by the manner in which the hepatic O2 supply is reduced and equally important, its timing relative to bacteremia. Brief secondary hypoxic stress of bufferperfused rat livers downregulates E. Coli (EC)induced TNF expression whereas lowflow ischemia preceding EC increases subsequent TNF production owing to reactive O2 species (ROS). Here we determined whether 30 min of constantflow hypoxia preceding 109 intraportal EC likewise increases antigenic and bioactive TNF protein concentrations during reoxygenation via production of ROS. Multiple groups (n=38) were studied over 180 minutes, circulation antigenic TNF decreased in H/R+EC vs. EC controls (1 939640 vs. 12 4072 476 g/L at t=180 min; P<001, along with TNF bioactivity). TNF protein were not restored to control levels in ALLO+H/R+EC. Thus, ECinduced hepatic TNF production and export is strongly O2dependent in intact liver regardless of the generation of ROS or the sequence of bacteremia and modest hypoxic stress.
