Effect of ischemia-reperfusion injury on the microcirculation of the steatotic liver of the Zucker rat

Background. Much discussion has been focused on the use of steatotic livers for transplantation due to the prevalence of steatosis in the potential do nor liver pool (1). The aim of this study was to investigate the possibilit y that the microcirculation of steatotic liver is more sensitive to the isc hemia-reperfusion (IR) injury than normal liver. Methods. The left liver lobe of obese (n=9) and lean ischemia followed by 6 0 min of reperfusion. Fluorescent probes rhodamine 123 (Rh123), bisbenzimid e (Bis), and rhodamine 6G (Rh6G) were administered for the identification b y intravital fluorescence microscopy (IVFM) of mitochondrial membrane poten tial, hepatocyte nuclei and leukocytes, respectively before hepatic ischemi a and at 15, 30, 45, and 60 min after reperfusion. Blood samples were obtai ned before and after 60 min of reperfusion. Liver tissue was taken at the e nd of experiment for histological analysis. Results. The liver of the obese rats showed prominent macro- and microvesic ular fatty changes (MAFC and MIFC) and hepatocyte swelling. Under IVFM, the obese animals had significantly wider hepatic cords (23.1 +/-0.8 mum) than the lean ones (15.9 +/-0.5 mum) (P<0.01), whereas no significant differenc e in sinusoidal diameters was noted. The number of functional sinusoids sig nificantly decreased after 30 min of reperfusion in both groups but no sign ificant change was noted in the nucleus count throughout the experiment. Rh 123 fluorescence intensity dropped significantly in the obese group after 6 0 min of reperfusion but not in the lean rats. Leukocyte adherence showed a significant rise after reperfusion in both groups. Plasma AST and ALT leve ls were 40- and 24-fold higher respectively for the obese animals after IR compared with their preischemic values, whereas the corresponding increase were 4.2- and 3.4-fold for the lean animals, respectively. Conclusions. Our results indicate that the liver of the obese Zucker rat is steatotic and presents with an abnormal microcirculation manifested by a r educed sinusoidal density. IR led to significantly greater hepatic injury i n the steatotic than in the normal liver. This injury was accompanied by a significant reduction in the functional sinusoidal density and mitochondria l membrane potential as assessed by Rh123-associated fluorescence in the st eatotic liver. In conclusion, the increased sensitivity of the steatotic li ver to IR injury would appear to involve both alterations in blood flow in the microcirculation. and to cellular changes.