Villeneuve J P, Dagenais M, Huet P M, Roy A, Lapointe R, Marleau D
Department of Medicine, Centre de recherche clinique André-Viallet, Hôpital Saint-Luc, Montreal, Quebec, Canada.
Hepatology. 1996 Jan;23(1):24-31. doi: 10.1002/hep.510230104.
In cirrhosis, capillarization of sinusoids could result in impaired exchanges 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 transplantation, and from organ donors with normal or near-normal livers or hepatic steatosis. In organ donors, the sinusoidal volume and the permeability of sinusoids to albumin, sucrose, and water were found to be comparable to that of normal dog and rat livers. The sinusoidal volume and the extravascular volume (EVV) accessible to diffusible tracers were larger after hepatic artery than after portal vein injection, probably because of an unshared arterial sinusoidal bed. In cirrhotic livers, two kinds of alterations were found: the appearance of a barrier between 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 between the hepatic extraction of indocyanine green (ICG) and the extravascular space accessible to albumin (r = .84, P < .05), suggesting that the impaired access of this protein-bound dye to the hepatocyte surface contributed to its impaired elimination. Intrahepatic shunts were found between portal and hepatic vein (21% +/- 16% of portal flow), but not between hepatic artery and hepatic veins. We conclude that (1) the behavior of diffusible tracers in human livers with normal liver architecture is comparable to that reported in normal animals; (2) the permeability of sinusoids in cirrhotic livers is abnormal, (3) permeability changes are related to changes in liver function in cirrhosis.
在肝硬化中，肝血窦的毛细血管化可导致肝细胞与灌注肝脏的血液之间的物质交换受损，进而导致肝衰竭，而与肝脏的代谢能力无关。为了表征肝微循环的异常情况，我们在移植时从肝硬化患者以及肝脏正常或接近正常或有肝脂肪变性的器官供体获取的离体灌注肝脏中使用了多指示剂稀释法。在器官供体中，发现肝血窦容积以及血窦对白蛋白、蔗糖和水的通透性与正常犬和大鼠肝脏相当。肝动脉注射后，可被可扩散示踪剂进入的肝血窦容积和血管外容积（EVV）比门静脉注射后更大，这可能是因为存在一个不共享的动脉血窦床。在肝硬化肝脏中，发现了两种改变：血窦与肝细胞之间出现屏障（毛细血管化）和肝内分流。随着肝硬化严重程度的增加，白蛋白可进入的血管外间隙减小，蔗糖在狄氏间隙中的扩散呈现屏障限制模式，而非正常的流量限制行为。在肝硬化肝脏中，发现吲哚菁绿（ICG）的肝摄取与白蛋白可进入的血管外间隙之间存在相关性（r = 0.84，P < 0.05），这表明这种与蛋白质结合的染料进入肝细胞表面的能力受损导致了其清除受损。在门静脉和肝静脉之间发现了肝内分流（占门静脉血流的21% ± 16%），但在肝动脉和肝静脉之间未发现。我们得出结论：（1）具有正常肝脏结构的人类肝脏中可扩散示踪剂的行为与正常动物中报道的行为相当；（2）肝硬化肝脏中血窦的通透性异常；（3）通透性变化与肝硬化中的肝功能变化相关。
