Tissue metabolism during endotoxin shock after pretreatment with monophosphoryl lipid A.
OBJECTIVE
Preconditioning pigs with low doses of monophosphoryl lipid A (MPL), a non toxic derivate of lipid A, has been shown to induce endotoxin hyporesponsiveness and to reduce the metabolic and hemodynamic consequences of endotoxin shock. However, the mechanism is presently unclear. This study was designed to elucidate the effects of pretreatment with MPL on tissue metabolism in different organs by in vivo microdialysis of interstitial fluid.


METHODS
In a controlled animal study at the university research laboratory, seven female mixed-breed pigs were exposed to an endotoxin infusion (1 microg/kg b.w. per h) after pretreatment with MPL in incremental doses of endotoxin during days 5-2 before the experiments. Seven animals receiving a saline pretreatment served as a control group. Hemodynamic variables and blood gas analyses including blood lactate were determined every 30 min until the animals died. Interstitial lactate and glycerol levels were measured in muscle, subcutaneous tissue and liver using in vivo microdialysis.


RESULTS
Survival time was significantly prolonged after MPL preconditioning (8.95 (7.5-9.1) h vs. 5.35 (5.0-5.6) h, P<0.05). Hemodynamic parameters were not significantly different between the treatment and control groups, while mixed venous saturation (81% (70-93%) vs. 30% (22-48%)) and arterial blood pH (7.39 (7.33-7.44) vs. 7.21 (7.1-7.25)) and pO(2) were significantly higher in the preconditioned group (P<0.05). The interstitial concentrations of lactate and glycerol in all investigated tissues were significantly higher in control animals than the those who had been pretreated with MPL (P<0.05).


CONCLUSIONS
Preconditioning with low doses of monosphosphoryl lipid A attenuates the negative effects of endotoxemia on tissue metabolism, probably by reducing O(2)-consumption. These changes may be subtle and, hence, only fully detectable by monitoring tissue metabolism.
Klaus
Stephan
S
Department of Anesthesiology, Medical University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. stephan.klaus@epost.de
Staubach
Karl H
KH
Heringlake
Matthias
M
Gliemroth
Jan
J
Schmucker
Peter
P
Bahlmann
Ludger
L
D000818:Animals; D004731:Endotoxins; D005260:Female; D005990:Glycerol / Q000032:analysis; D019344:Lactic Acid / Q000032:analysis; D008050:Lipid A / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism*; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism*; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism*; D040521:Subcutaneous Tissue / Q000378:metabolism; D013552:Swine; D013997:Time Factors
D004731:Endotoxins; D008050:Lipid A; D019344:Lactic Acid; C048436:monophosphoryl lipid A; D005990:Glycerol