Relationship between the lung and systemic response to endotoxin: comparison of physiologic change and the degree of lipid peroxidation.

The lung and systemic response to Escherichia coli endotoxin either 2 or 5 micrograms/kg was measured in 16 sheep with chronic lung and soft tissue lymph fistulae. Oxidant-induced lung and liver lipid peroxidation was measured as tissue malondialdehyde (MDA). Conjugated dienes were also monitored. Both doses produced a comparable pulmonary hypertension and hypoxia as well as a comparable increase in protein-rich lymph flow, QL. However, lung MDA was significantly greater with the 5 micrograms/kg than with the 2 micrograms/kg dose, both being more than twofold greater than controls. The systemic physiologic responses between the two doses were quite different. The 5 microgram/kg dose resulted in a significant increase in oxygen delivery (DO2), oxygen consumption (VO2), and decrease in arterial O2 extraction in the 3-5 hr postendotoxin period compared with the 2 microgram/kg dose. A twofold increase in protein-rich soft tissue QL was also seen after the 5 micrograms/kg dose, whereas QL was not changed after 2 micrograms/kg. Liver MDA was only increased by 30% over controls with both doses. We conclude that the relationship between oxidant change and physiologic response varies considerably between lung and systemic tissues after endotoxemia with the degree of lung lipid peroxidation corresponding with the degree of impairment in systemic tissue O2 extraction and the onset of delivery-dependent O2 consumption.