BACKGROUND/AIMS: 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.
BACKGROUND/AIMS: 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.
Authors: Christian Eipel; Matthias Glanemann; Andreas K Nuessler; Michael D Menger; Peter Neuhaus; Brigitte Vollmar Journal: Ann Surg Date: 2005-03 Impact factor: 12.969
Authors: Niteen Tapuria; Sameer Junnarkar; Mahmoud Abu-Amara; Barry Fuller; Alexander M Seifalian; Brian R Davidson Journal: HPB (Oxford) Date: 2011-11-27 Impact factor: 3.647
Authors: Friedrich Duenschede; Kirsten Erbes; Nina Riegler; Patrick Ewald; Achim Kircher; Stefanie Westermann; Arno Schad; Imke Miesmer; Simon Albrecht-Schöck; Ines Gockel; Alexandra K Kiemer; Theodor Junginger Journal: World J Gastroenterol Date: 2007-07-21 Impact factor: 5.742