Arterial and hepatovenous concentrations of circulating prostaglandin Ez and prostaglandin Fzm, the stable metabolites of prostacyclin and thromboxane Az were measured in patients with chronic liver disease and compared with those in control patients with coronary artery disease but without hepatic dysfunction. Specific radioimmunoassays were used after extraction on octadecyl C 18-silica gel columns and thin-layer chromatography. While low levels of all cyclooxygenase products were found in hepatic arterial blood in patients with proven cirrhosis (n = 10) and fibrosis (n = 8), significantly higher concentrations were detected in the hepatic vein. A similar concentration profile was observed in controls (n = 4). Thus, there is a marked but comparable release of prostanoids from the normal as well as the diseased liver. Hepatovenous prostaglandin Ez was 11.6-fold, prostaglandin Fz, was 7.5-fold, prostacyclin was 12.2.-fold and thromboxane Bz was 3.9-fold above the level in the artery in both groups of patients. The hepatovenous concentrations of all arachinodate metabolites were unrelated to changes of liver morphology, biochemical abnormalities or the presence of ascites. No correlation could be demonstrated between hepatic venous pressure gradient and the concentration of prostanoids in the hepatic vein with the exception of thromboxane Bs (r = 0.55, p < 0.06). The Occurrence of esophageal varices was not associated with a specific pattern of circulating prostanoids in the posthepatic vasculature. Moreover, the portal-venous concentrations of all prostanoids (five patients: two with fibrosis, three with cirrhosis) exceeded the level in the hepatic vein substantially.
While the functional significance of high levels of arachinodate metabolites in the hepatic and portal vein remains questionable, excessive release of prostanoids from the prehepatic splanchnic area occurs in advanced stages of chronic liver disease as well as in patients with minor morphological changes and apparently in healthy subjects, too. We suggest that the high content of prostanoids in the portal vein primarily reflects its predominant role in regulating gastrointestinal motility as well as in regulating splanchnic microcirculation.
Metabolites of arachidonic acid with vasodilatory properties such as prostaglandin E, (PGE,) and prostacyclin (PGI,) and those exhibiting vasoconstrictor effects