Ischemic preconditioning protects from hepatic ischemia/reperfusion-injury by preservation of microcirculation and mitochondrial redox-state

Abstract

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.