Thoracic epidural anesthesia reverses sepsis-induced hepatic hyperperfusion and reduces leukocyte adhesion in septic rats.
BACKGROUND
Liver dysfunction is a common feature of severe sepsis and is associated with a poor outcome. Both liver perfusion and hepatic inflammatory response in sepsis might be affected by sympathetic nerve activity. However, the effects of thoracic epidural anesthesia (TEA), which is associated with regional sympathetic block, on septic liver injury are unknown. Therefore, we investigated hepatic microcirculation and inflammatory response during TEA in septic rats.


METHODS
Forty-five male Sprague-Dawley-rats were instrumented with thoracic epidural catheters and randomized to receive a sham procedure (Sham), cecal ligation and puncture (CLP) without epidural anesthesia (Sepsis) and CLP with epidural infusion of 15 ul/h bupivacaine 0.5% (Sepsis + TEA). All animals received 2 ml/100 g/h NaCl 0.9%. In 24 (n = 8 in each group) rats, sinusoidal diameter, loss of sinusoidal perfusion and sinusoidal blood flow as well as temporary and permanent leukocyte adhesion to sinusoidal and venolar endothelium were recorded by intravital microscopy after 24 hours. In 21 (n = 7 in each group) separate rats, cardiac output was measured by thermodilution. Blood pressure, heart rate, serum transaminase activity, serum TNF-alpha concentration and histologic signs of tissue injury were recorded.


RESULTS
Whereas cardiac output remained constant in all groups, sinusoidal blood flow increased in the Sepsis group and was normalized in rats subjected to sepsis and TEA. Sepsis-induced sinusoidal vasoconstriction was not ameliorated by TEA. In the Sepsis + TEA group, the increase in temporary venolar leukocyte adherence was blunted. In contrast to this, sinusoidal leukocyte adherence was not ameliorated in the Sepsis + TEA group. Sepsis-related release of TNF-alpha and liver tissue injury were not affected by Sepsis + TEA.


CONCLUSIONS
This study demonstrates that TEA reverses sepsis-induced alterations in hepatic perfusion and ameliorates hepatic leukocyte recruitment in sepsis.
Freise
Hendrik
H
Department of Anesthesiology and Intensive Care, University Hospital of Muenster, Albert-Schweitzer-Strasse 33, 48149 Muenster, Germany. freiseh@uni-muenster.de
Daudel
Fritz
F
Grosserichter
Christina
C
Lauer
Stefan
S
Hinkelmann
Juergen
J
Van Aken
Hugo K
HK
Sielenkaemper
Andreas W
AW
Westphal
Martin
M
Fischer
Lars G
LG
D000767:Anesthesia, Epidural; D000818:Animals; D002302:Cardiac Output; D002448:Cell Adhesion; D004195:Disease Models, Animal; D007962:Leukocytes / Q000166:cytology*; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D013904:Thoracic Vertebrae; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha