The American journal of pathology
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Hepatic ischemia-reperfusion (I/R) is characterized by circulatory and metabolic derangements, liver dysfunction, and tissue damage. However, little is known about the causative role of I/R-induced microcirculatory disturbance on the manifestation of postischemic reperfusion injury. Therefore, the intention of the study was to assess changes of hepatic microvascular perfusion (intravital fluorescence microscopy) as related to hepatic morphology (light/electron microscopy), hepatocellular integrity (serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities), and excretory function (bile flow). ⋯ Prolongation of lobar ischemia (group C, 60 minutes) aggravated postischemic reperfusion injury (sinusoidal perfusion rate: 87.4 +/- 2.9%; erythrocyte flux: 62.1 +/- 8.4%) and was paralleled by severed hepatocellular damage. Electron microscopy of postischemic tissue demonstrated alteration of nonparenchymal cells (swelling of sinusoidal lining cells and widening of Disse's space) and substantial parenchymal cell damage (swelling of mitochondria, disarrangement of rough endoplasmatic reticulum, vacuolization, complete cytoplasmic degeneration). Initial postischemic increase in serum AST and ALT activities and reduction of bile flow directly correlated with the extent of microcirculatory failure (P < 0.01), ie, impairment of sinusoidal perfusion and decrease of erythrocyte flux, indicating the decisive role of microvascular perfusion failure for the manifestation of hepatic tissue damage and liver dysfunction.