THE HEPATIC MICROCIRCULATION IN THE ISOLATED-PERFUSED HUMAN LIVER

In cirrhosis, capillarization of sinusoids could result in impaired ex changes between the hepatocytes and the blood perfusing the liver and contribute to liver failure irrespective of the metabolic capacity of the Liver, To characterize anomalies of the hepatic microcirculation, we used the multiple-indicator dilution approach in isolated perfused Livers obtained from patients with cirrhosis at the time of transplant ation, and hom organ donors with normal or near-normal livers or hepat ic steatosis. In organ donors, the sinusoidal volume and the permeabil ity of sinusoids to albumin, sucrose, and water were found to be compa rable to that of normal dog and rat Livers, The sinusoidal volume and the extravascular volume (EVV) accessible to diffusible tracers were l arger after hepatic artery than after portal vein injection, probably because of an unshared arterial sinusoidal bed, In cirrhotic livers, t wo kinds of alterations were found: the appearance of a barrier betwee n the sinusoids and the hepatocytes (capillarization) and intrahepatic shunts, The extravascular space accessible to albumin decreased with increasing severity of cirrhosis, and the diffusion of sucrose in the space of Disse showed a barrier-limited pattern, instead of the normal flow-limited behavior, In cirrhotic livers, a correlation was found b etween the hepatic extraction of indocyanine green (ICG) and the extra vascular space accessible to albumin (r = .84, P < .05), suggesting th at the impaired access of this protein-bound dye to the hepatocyte sur face contributed to its impaired elimination, Intrahepatic shunts were found between portal and hepatic vein (21% +/- 16% of portal now), bu t not between hepatic artery and hepatic veins, We conclude that (1) t he behavior of diffusible tracers in human livers with normal liver ar chitecture is comparable to that reported in normal animals; (2) the p ermeability of sinusoids in cirrhotic livers is abnormal, (3) permeabi lity changes are related to changes in liver function in cirrhosis.