title: Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion.
abstract: 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). Sprague-Dawley rats were subjected to 20 minutes (group B, n = 9) and 60 minutes (group C, n = 9) of left hepatic lobar ischemia followed by 60 minutes of reperfusion. Sham-operated animals without ischemia served as controls (group A, n = 10). Lobar ischemia for 20 minutes followed by reperfusion resulted in a significant reduction of sinusoidal perfusion rate (93.9 +/- 1.4%; P < 0.05) and a decrease in erythrocyte flux (90.0 +/- 5.6%) when compared with controls (99.4 +/- 0.2 and 97.9 +/- 2.7%). This was accompanied by a significant increase of serum AST and ALT activities (P < 0.05) and a reduction of bile flow (P < 0.05). 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.
authors.affiliation: Institute for Surgical Research, University of Munich, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Vollmar
authors.forename: J
authors.initials: J
authors.lastname: Glasz
authors.forename: R
authors.initials: R
authors.lastname: Leiderer
authors.forename: S
authors.initials: S
authors.lastname: Post
authors.forename: M D
authors.initials: MD
authors.lastname: Menger
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000502:physiology; D001775:Blood Circulation; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008099:Liver / Q000473:pathology / Q000503:physiopathology*; D008102:Liver Circulation; D008297:Male; D008833:Microcirculation; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013696:Temperature; D017211:Treatment Failure
chemical_list: D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase