Endotoxemia produces an increase in arterial but not venous lipid peroxides in sheep

Abstract

Our purpose was to determine the effect of an endotoxin-induced lung injury on circulating lipid peroxides. We measured both malonidialdehyde (MDA) and conjugated dienes (as optical density at 233 nm) in aortic and venous plasma and lung lymph in 10 unanesthetized sheep given 1 .mu.g/kg of Escherichia coli endotoxin. Total lipids and prostanoids 6-ketoprostaglandin F1.alpha. and thromboxane B2 were also measured. Six control sheep were also studied. Animals were monitored for a 12-h period and then killed, and lung tissue MDA was determined. A two-phase endotoxin response was noted with an initial pulmonary hypertension followed by a steady-state increase in protein-rich lung lymph flow (.ovrhdot.QL) between a 3- and 6-h period. Aortic plasma MDA was significantly increased from a base line of 4.8 .+-. 1.4 to 8.9 .+-. 1.6 and 7.5 .+-. 1.3 nmol/ml at 1 and 4 h post-endotoxin. Aortic plasma conjugated dienes increases in all 10 sheep post-endotoxin. Venous levels of both MDA and conjugated dienes were not significantly increased. Lung .ovrhdot.QL increased two- to three-fold. Lung lymph MDA increased significantly at 1 h post-endotoxin. Lymph conjugated dienes decreased. Plasma and lymph lipid peroxide levels returned to base line by 12 h in most animals. However, tissue MDA remained significantly increased in all sheep from base line of 45 .+-. 9 to 85 .+-. 14 nmol/g tissue. we conclude that both MDA and conjugated dienes are transiently released into aortic plasma during endotoxin-induced oxidant lung injury. The peroxides appear to be rapidly cleared since they are not significantly increased in venous plasma. Residual tissue lipid peroxidation remains beyond the period of increased circulating lipid peroxides.