Decreased lactate in endotoxin-resistant mice undergoing hemorrhage is independent of tumor necrosis factor availability.
Although C3H/HeJ mice, characterized by a genetic deficiency in macrophage cytokine release in response to endotoxin, have been studied extensively to gain insight into the possible role of various cytokines in sepsis, few past studies have examined the physiologic response to hemorrhagic shock in this "endotoxin-resistant" strain. We utilized a fixed-volume model of hemorrhagic shock and two different levels of hemorrhage severity (50 and 67% blood volume) to compare C3H/HeJ mice to normal C3H/HeN mice. An additional group of endotoxin-sensitive C3H/HeN mice were treated with 2.5 mg/kg of anti-tumor necrosis factor (TNF) antibody to define the possible role of TNF in shock physiology. Hematocrit, circulating neutrophils, and plasma glucose and lactate concentrations were measured following hemorrhage. TNF increased significantly following hemorrhage in normal mice but did not increase in C3H/HeJ mice or in C3H/HeN mice treated with anti-TNF antibody. No difference between groups was identified in hematocrit, circulating neutrophils, or glucose. Whereas plasma lactate increased significantly by 30 min in all groups, lactate returned to baseline levels in C3H/HeJ mice at 60 min, but remained persistently elevated in C3H/HeN mice and in C3H/HeN mice treated with anti-TNF antibody. The data demonstrate attenuated lactate accumulation in C3H/HeJ mice following hemorrhage. Inhibition of circulating TNF activity with anti-TNF antibody failed to reproduce this late decrease in plasma lactate in normal mice. The data suggest that macrophage products other than TNF known to be deficient in C3H/HeJ mice contribute to anaerobic metabolism in hemorrhagic shock.
Pellicane
J V
JV
Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
Gore
D C
DC
DeMaria
E J
EJ
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004351:Drug Resistance; D004731:Endotoxins / Q000494:pharmacology*; D006400:Hematocrit; D006470:Hemorrhage / Q000097:blood* / Q000503:physiopathology; D007773:Lactates / Q000097:blood*; D019344:Lactic Acid; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
D001786:Blood Glucose; D004731:Endotoxins; D007773:Lactates; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid