The influence of organ temperature on hepatic ischemia-reperfusion injury: a systematic analysis.
BACKGROUND
Although hepatic ischemia-reperfusion (I/R) injury can be reduced by cooling of the ischemic organ, a systematic in vivo analysis of the influence of organ temperature in I/R injury is missing. The aim of this study was to systematically investigate the impact of defined temperatures of the ischemic liver tissue on microvascular I/R injury.


METHODS
Ischemia of the left liver lobe was induced in C57BL/6 mice for 90 min. The ischemic lobe was placed in a polyethylene well and the temperature was adjusted to 37 degrees C, 26 degrees C, 15 degrees C, and 4 degrees C by superfusion with cooled/warmed saline solution. The ischemia groups (n=7 each) were compared with a sham-operated group (n=7). The sinusoidal perfusion index and the number of leukocytes firmly adherent to the endothelium of postsinusoidal venules were assessed using intravital fluorescence microscopy at 30 min, 120 min, and 240 min of reperfusion, respectively. At the end of the experiment, serum activities of the liver enzymes aspartate aminotransferase/alanine aminotransferase were determined, and tissue specimens were examined by electron microscopy.


RESULTS
Core body temperature did not differ significantly between the groups. In the 37 degrees C group, the sinusoidal perfusion index was significantly reduced and the number of adherent leukocytes was significantly increased compared with the sham group. In all hypothermia groups, however, the microcirculatory parameters did not differ from the sham group. Serum activities of aspartate aminotransferase/alanine aminotransferase were significantly increased and hepatocellular integrity was severely affected in the 37 degrees C group as compared with all other groups.


CONCLUSIONS
These findings demonstrate that in the mouse liver the known protective effect of hypothermia is already encountered at 26 degrees C. Further reduction of temperature did not generate additional protection from I/R injury.
Biberthaler
P
P
Institute for Surgical Research, University of Munich, Germany. bibe@ch-i.med.uni-muenchen.de
Luchting
B
B
Massberg
S
S
Teupser
D
D
Langer
S
S
Leiderer
R
R
Messmer
K
K
Krombach
F
F
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001831:Body Temperature; D002448:Cell Adhesion; D003911:Dextrans; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D007962:Leukocytes / Q000502:physiology; D008099:Liver / Q000098:blood supply* / Q000648:ultrastructure; D008102:Liver Circulation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology*; D008856:Microscopy, Fluorescence; D012016:Reference Values; D015427:Reperfusion Injury / Q000503:physiopathology*; D014699:Venules / Q000503:physiopathology
D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D016650:Fluorescein-5-isothiocyanate