Ischemic preconditioning protects from hepatic ischemia/reperfusion-injury by preservation of microcirculation and mitochondrial redox-state.
OBJECTIVE
Ischemic preconditioning (IP) is known to protect hepatic tissue from ischemia-reperfusion injury. However, the mechanisms involved are not fully understood yet.


METHODS
Using intravital multifluorescence microscopy in the rat liver, we studied whether IP exerts its beneficial effect by modulating postischemic Kupffer cell activation, leukocyte-endothelial cell interaction, microvascular no-reflow, mitochondrial redox state, and, thus, tissue oxygenation.


RESULTS
Portal triad cross-clamping (45 min) followed by reperfusion induced Kupffer cell activation, microvascular leukocyte adherence, sinusoidal perfusion failure (no-reflow) and alteration of mitochondrial redox state (tissue hypoxia) (P<0.05). This resulted in liver dysfunction and parenchymal injury, as indicated by decreased bile flow and increased serum glutamate dehydrogenase (GLDH) levels (P<0.05). IP (5 min ischemia and 30 min intermittent reperfusion) was capable to significantly reduce Kupffer cell activation (P<0.05), which was associated with a slight attenuation of leukocyte adherence. Further, IP markedly ameliorated sinusoidal perfusion failure (P<0.05), and, thereby, preserved adequate mitochondrial redox state (P<0.05). As a consequence, IP prevented the decrease of bile flow (P<0.05) and the increase in serum GLDH levels (P<0.05).


CONCLUSIONS
IP may exert its beneficial effects on hepatic ischemia-reperfusion injury by preserving mitochondrial redox state, which is guaranteed by the prevention of reperfusion-associated Kupffer cell activation and sinusoidal perfusion failure.
Glanemann
Matthias
M
Department of General, Visceral and Transplantation Surgery, Charité, Campus Virchow Klinikum, Humboldt University Berlin, Berlin, Germany.
Vollmar
Brigitte
B
Nussler
Andreas K
AK
Schaefer
Thilo
T
Neuhaus
Peter
P
Menger
Michael D
MD
D000818:Animals; D002448:Cell Adhesion; D019194:Ischemic Preconditioning; D007728:Kupffer Cells / Q000502:physiology; D007962:Leukocytes / Q000502:physiology; D008099:Liver / Q000378:metabolism / Q000502:physiology; D008102:Liver Circulation; D008297:Male; D008833:Microcirculation; D008930:Mitochondria, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010587:Phagocytosis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D010100:Oxygen