Impact of antithrombin III on hepatic and intestinal microcirculation in experimental liver cirrhosis and bowel inflammation: Anin vivoanalysis

Abstract

To analyze the hepatic and intestinal microcirculation in an animal model of liver cirrhosis and inflammatory bowel disease (IBD) and to characterize the anti-inflammatory action of antithrombin III (ATIII) on leukocyte kinetics and liver damage. Hepatic and intestinal microcirculation was investigated by intravital videomicroscopy. Standardized models of experimental chronic liver cirrhosis and bowel inflammation were employed. Animals were divided into four groups (n = 6/group): controls, animals with cirrhosis, animals with cirrhosis and IBD, animals with cirrhosis and IBD treated with ATIII. Cirrhosis facilitated leukocyte rolling and sticking in hepatic sinusoids (1.91+/-0.28 sticker/microm vs 0.5+/-0.5 sticker/microm in controls, P<0.05). The effect enhanced in animals with cirrhosis and IBD (5.4+/-1.65 sticker/microm), but reversed after ATIII application (3.97+/-1.04 sticker/microm, P<0.05). Mucosal blood flow showed no differences in cirrhotic animals and controls (5.3+/-0.31 nL/min vs 5.4+/-0.25 nL/min) and was attenuated in animals with cirrhosis and IBD significantly (3.49+/-0.6 nL/min). This effect was normalized in the treatment group (5.13+/-0.4 nL/min, P<0.05). Enzyme values rose during development of cirrhosis and bowel inflammation, and reduced after ATIII application (P<0.05). Liver cirrhosis in the presence of IBD leads to a significant reduction in mucosal blood flow and an increase in hepatic leukocyte adherence with consecutive liver injury, which can be prevented by administration of ATIII.