Hepatic effects of thoracic epidural analgesia in experimental severe acute pancreatitis.
BACKGROUND
Thoracic epidural anesthesia (TEA) protects the intestinal microcirculation and improves perioperative outcomes. TEA also reduces mortality in acute experimental pancreatitis. Its impact on hepatic microcirculation, however, in health and critical illness is unknown. Therefore, the authors studied the effect of TEA on the liver in healthy rats and in experimental severe acute pancreatitis.


METHODS
TEA was induced by 15 microl/h bupivacaine, 0.5%. Necrotizing pancreatitis was induced by intraductal infusion of 2 ml/kg taurocholic acid, 5%. Twenty-eight rats were assigned to either Sham operation, Sham + TEA, Pancreatitis, or Pancreatitis + TEA. After 15 h, mean arterial pressure, heart rate, and respiratory function were recorded. Sinusoidal width and perfusion rate and the intrahepatic leukocyte adhesion were assessed by intravital microscopy. In an additional 22 rats randomly assigned to Sham, Pancreatitis, and Pancreatitis + TEA, hepatic apoptosis was evaluated by staining for single-stranded DNA and Fas ligand-positive cells.


RESULTS
TEA did not affect hepatic microcirculation and leukocyte adhesion in healthy rats. Blood pressure remained unchanged in the Sham + TEA group. In Pancreatitis, mean arterial pressure decreased from 141 + or - 6 mmHg to 127 + or - 13 mmHg but remained stable in Pancreatitis + TEA. The sinusoidal diameter decreased from 5.4 + or - 0.1 microm to 5.0 + or - 0.2 microm in Pancreatitis. This was restored in Pancreatitis + TEA. Intrahepatic leukocyte adhesion was not affected by TEA. The increased hepatocyte apoptosis in Pancreatitis was abolished in Pancreatitis + TEA. This might be mediated by inhibition of the Fas ligand pathway.


CONCLUSIONS
TEA reduces liver injury in necrotizing acute pancreatitis. This could be related to a regional sympathetic block. TEA could thus preserve liver function in systemic inflammatory disorders such as acute pancreatitis.
Freise
Hendrik
H
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Muenster, Albert Schweitzer Strasse 33, 48149 Muenster, Germany. freiseh@uni-muenster.de
Lauer
Stefan
S
Konietzny
Eva
E
Hinkelmann
Juergen
J
Minin
Evgeni
E
Van Aken
Hugo K
HK
Lerch
Markus M
MM
Sielenkaemper
Andreas W
AW
Fischer
Lars G
LG
D000208:Acute Disease; D015360:Analgesia, Epidural / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D016638:Critical Illness; D053222:Fas Ligand Protein / Q000378:metabolism; D006439:Hemodynamics / Q000502:physiology; D006614:Hindlimb / Q000502:physiology; D007813:Laparotomy; D008099:Liver / Q000187:drug effects*; D008102:Liver Circulation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009068:Movement / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010195:Pancreatitis / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D053222:Fas Ligand Protein; D002245:Carbon Dioxide; D010100:Oxygen