Didier Lebrec

Cirrhotic rats with bacterial translocation have higher incidence and severity of hepatopulmonary syndrome.

Background:u2002 Bacterial translocation, that is, extra‐intestinal dissemination of gut bacteria, occurs in approximately 50% of humans and rats with cirrhosis and plays a significant role in enhanced tumor necrosis factor‐α (TNF‐α) production. The authors’ previous studies have indicated that prevention of bacterial translocation with norfloxacine or inhibition of TNF‐α with pentoxifylline treatment decreased both the incidence and severity of hepatopulmonary syndrome by attenuating the induction of pulmonary intravascular macrophages in cirrhotic rats. In the present study the hypothesis was tested that the cirrhotic rats with bacterial translocation had higher TNF‐α production, higher level of sequestration of macrophages in pulmonary vessels, and increased incidence and severity of hepatopulmonary syndrome.

Discrepant effects of inducible nitric oxide synthase modulation on systemic and splanchnic endothelial nitric oxide synthase activity and expression in cirrhotic rats.

Background:u2002 Arterial vasodilatation, which is a major factor in the pathogenesis of the hyperkinetic circulatory state and portal hypertension in cirrhosis, is due to arterial nitric oxide (NO) overproduction secondary to endothelial NO synthase (eNOS) and inducible NOS (iNOS) upregulation. However, in cirrhosis, the respective roles of eNOS and iNOS isoforms in NO overproduction are still unknown and the effect of iNOS modulation on eNOS activity and expression has not been evaluated in the systemic or splanchnic vessels. The aim of this study was to evaluate the effects of modulating aortic and superior mesenteric arteries (SMA) iNOS on arterial eNOS activity and expression in rats with cirrhosis.

Molecular Mechanisms of Systemic Vasodilation and Hyperdynamic Circulatory State of Cirrhosis

Portal hypertension due to cirrhosis is associated with a chronic hyperkinetic syndrome (1, 2, 3). This syndrome is characterized by elevated cardiac output, low arterial pressure, and low systemic vascular resistance (2,3). Splanchnic circulation is also hyperdynamic, i.e., blood flow is elevated and vascular resistance is low in arteries that supply splanchnic organs (1,4). Systemic and splanchnic alterations are interrelated: decreased systemic vascular resistance (systemic vasodilation) is largely due to the decrease in splanchnic arterial resistance (splanchnic vasodilation) (5). Finally, in cirrhosis, there is in vivo and ex vivo arterial hyporeactivity to different receptor-dependent and -independent vasoconstrictors (6, 7, 8, 9, 10, 11, 12, 13, 14). A hyperkinetic syndrome also occurs in extrahepatic portal hypertension (15), but it is less marked than that observed in cirrhosis.