Thalidomide decreases intrahepatic resistance in cirrhotic rats

Increased intrahepatic resistance (IHR) within cirrhotic liver is caused by increased endotoxemia, cytokines tumor necrosis factor-α (TNF-α), vasoconstrictor thromboxane A₂ (TXA₂), and disrupted microvasculatures. We evaluated the effects of thalidomide-related inhibition of TNF-α upon the hepatic microcirculation of cirrhosis in rats. Portal venous pressure (PVP), hepatic TNF-α, expression of thromboxane synthase (TXS), and leukocyte common antigen (LCA) were measured in bile-duct-ligated (BDL) rats receiving 1 month of thalidomide (BDL-thalido rats). Portal perfusion pressure (PPP), IHR, and hepatic TXA₂ production were measured in the isolated liver perfusion system. Intravital microscopy was used to examine hepatic microvascular disruptions. In BDL-thalido rats, PVP, PPP, IHR, hepatic TXA₂ and TNF-α, hydroxyproline content, expression of TXS and LCA, and LPS-induced leukocyte recruitment were significantly decreased. Conversely, hepatic microvascular density and perfused sinusoids were significantly increased. Thalidomide decreased PVP and IHR by reducing hepatic TXA₂ and improving hepatic microvascular disruptions in rats with biliary cirrhosis.