Beneficial effects of ischemic preconditioning in patients undergoing hepatectomy: the role of neutrophils.
OBJECTIVE
Temporary vascular clampage (Pringle maneuver) during liver surgery can cause ischemia-reperfusion injury. In this process, activation of polymorphonuclear leukocytes (PMNLs) might play a major role. Thus, we investigated the effects of hepatic ischemic preconditioning on PMNL functions.


METHODS
Prospective randomized study. Patients who underwent partial liver resection were randomly assigned to 3 groups: group 1 without Pringle maneuver; group 2 with Pringle maneuver, and group 3 with ischemic preconditioning using 10 minutes of ischemia and 10 minutes of reperfusion prior to Pringle maneuver for resection.


METHODS
University hospital, Munich, Germany.


METHODS
Seventy-five patients underwent hepatic surgery mostly owing to metastasis.


METHODS
Perioperative factors for PMNL activation, inflammation, and postoperative hepatocellular integrity.


RESULTS
Ischemia-reperfusion of the human liver (mean +/- SD time to perform the Pringle maneuver, 35.5 +/- 2.6 minutes) caused (1) a decrease in the number of circulating PMNLs, (2) their intrahepatic sequestration, (3) their systemic activation, and (4) a significant correlation between the degree of their postischemic activation and the postoperative rise in liver enzyme serum levels. In parallel, cytokines with proinflammatory and chemotactic properties were released reaching the highest values when stimulation of PMNLs was most pronounced. When ischemic preconditioning preceded the Pringle maneuver, activation of PMNLs and cytokine plasma levels was reduced as evidenced by the attenuation of superoxide anion production, beta(2)-integrin up-regulation, and interleukin 8 serum concentrations, followed by a significant reduction in serum alanine aminotransferase levels on the first and second postoperative days.


CONCLUSIONS
These results demonstrate in humans that ischemic preconditioning reduces activation of PMNLs elicited by the Pringle maneuver. The down-regulation of potentially cytotoxic functions of PMNLs might be one of yet unknown important pathways that altogether mediate protection by ischemic preconditioning.
Choukèr
Alexander
A
Department of Anesthesiology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Martignoni
André
A
Schauer
Rolf
R
Dugas
Martin
M
Rau
Horst-Günther
HG
Jauch
Karl-Walter
KW
Peter
Klaus
K
Thiel
Manfred
M
D018821:CD18 Antigens / Q000097:blood; D005260:Female; D006498:Hepatectomy; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D019194:Ischemic Preconditioning; D008113:Liver Neoplasms / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000502:physiology; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000097:blood; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000503:physiopathology*
D018821:CD18 Antigens; D016209:Interleukin-8; D009195:Peroxidase