Influence of C1-esterase inhibitor on tissue oxygenation of jejunal mucosa during endotoxemia.
BACKGROUND
The complement system has been shown to play an important role in the pathogenesis of microcirculatory disturbances in trauma and sepsis. The intestinal mucosa is the most susceptible portion of the gut to impaired perfusion and oxygen delivery. The objective of this study was to investigate the effects of C1-esterase inhibitor (C1-INH) on arterial oxygenation (PaO2) and tissue oxygenation (PtiO2) of jejunal mucosa during endotoxemia.


METHODS
Eighteen anesthetized and ventilated rats were laparotomized and a jejunal portion was exteriorized and fixed on a plexiglass stage. The jejunum was punctured and a Clark type microcatheter PO2 probe and a micro thermocouple were placed on the mucosa in order to measure PtiO2. The animals were randomly assigned to receive one of the three treatments: infusion of Escherichia coli lipopolysaccharides (LPS) without C1-INH pretreatment (LPS group); or infusion of LPS with C1-INH pretreatment (C1-INH group); the control group (n = 6) without treatment of either C1-INH or LPS. The mean arterial pressure (MAP), heart rate (HR), PaO2 and PtiO2 were measured at baseline, 60 and 120 min after induction of endotoxemia.


RESULTS
Hemodynamic parameters (MAP, HR) in all the three groups showed no significant changes during the study period. PaO2 significantly decreased in the LPS group. This decrease could be attenuated by pretreatment with C1-INH. The mucosal PtiO2 of the jejunum in the control group remained stable. It significantly decreased in the LPS and in the C1-INH groups without showing a significant difference after 120 min of endotoxemia.


CONCLUSIONS
Pretreatment with C1-INH was able to diminish a decrease in PaO2 during endotoxemia, indicating that pulmonary injury was attenuated. Endotoxin-induced tissue hypoxia of the intestinal mucosa could not be prevented suggesting a minor involvement of complement activation in this pathophysiological process.
Schmidt
W
W
Department of Anesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany. werner.schmidt@urz.uni-heidelberg.de
Stenzel
K
K
Walther
A
A
Gebhard
M M
MM
Martin
E
E
Schmidt
H
H
D000818:Animals; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D019446:Endotoxemia / Q000378:metabolism*; D006439:Hemodynamics; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000097:blood / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D003174:Complement C1 Inactivator Proteins; D010100:Oxygen