Endothelin-3 like immunoreactivity in plasma of patients with cirrhosis of the liver

A highly specific and sensitive radioimmunoassay (RIA) has been established for determination of endothelin-3 like immunoreactivity in human plasma to investigate its possible role in hemodynamic alterations due to liver disease. Crossreactivity with other endothelin isoforms was always below 4 %, the lower detection limit following extraction on Sep-Pak C18 cartridges was 0.5 pg/ml. The concentration of endothelin-3 (mean ± SEM) was 4.16 ± 0.56 pg/ml (n = 13) in plasma of patients with cirrhosis of the liver, three fold higher than in age matched controls (1.35 ± 0.27 pg/ml, n = 12, p < 0.01). Plasma immunoreactivity was confirmed to be endothelin-3 related by reverse-phase HPLC. These data could suggest a role of plasma endothelin-3 in circulatory changes, as they occur in cirrhosis of the liver

Water immersion increases the concentration of the immunoreactive N-terminal fragment of pro-atrial natriuretic factor in human plasma

Atrial natriuretic factor (ANF) N-terminal (ANF 1–98) and C-terminal (ANF 99–126) fragments were determined by radioimmunoassay in human plasma. Mean basal plasma ANF N-terminal concentrations in 9 healthy subjects were 461 ± 58 fmol/ml,significantly (p<0.0001) higher than ANF C-terminal concentrations ( 4.8 ± 0.5 fmol/ml). Central volume stimulation by one hour head-out water immersion (WI) induced a significant (p<0.01) increase of the C-terminal peptide levels to 11.6 ± 2.3 fmol/ml,paralleled by a significant (p<0.001) increase of the N-terminal fragment levels to 749 ± 96 fmol/ml. Increases of plasma concentrations of both fragments upon WI correlated significantly (r=0.71;p<0.05). These data suggest cosecretion of the N-terminal fragment with the C-terminal fragment of pro ANF 1–126 following a physiological stimulus of ANF release in man

Role of the liver in splanchnic extraction of atrial natriuretic factor in the rat

Mesenteric, hepatic and splanchnic extraction of C-terminal and N-terminal atrial natriuretic factor was investigated in male Sprague-Dawley rats. Plasma concentrations (mean ± S.E.M.) of C-terminal atrial natriuretic factor were 55.0 ± 6.1 fmol/ml, 31.2 ± 4.0 fmol/ml and 23.5 ± 3.3 fmol/ml (n = 12) in the abdominal aorta, the portal vein and the hepatic vein, respectively. N-terminal atrial natriuretic factor plasma levels in these vessels were 3031 ± 756 fmol/ml, 2264 ± 661 fmol/ml and 1618 ± 496 fmol/ml (n = 6), respectively. Although the mesenteric extraction ratio was higher (p < 0.05) for C-terminal atrial natriuretic factor (42% ± 6%) than for N-terminal atrial natriuretic factor (28% ± 4%), there were no significant differences in the hepatic extraction ratio (41% ± 5% vs. 39% ± 6%) and the splanchnic extraction ratio (56% ± 5% vs. 50% ± 7%). These data suggest a major role of the liver in the splanchnic extraction of C-terminal and of N-terminal atrial natriuretic factor in the rat. (HEPATOLOGY 1992;16:790-793

Atrial natriuretic factor (ANF) and renin-aldosterone in volume regulation of patients with cirrhosis

The role of the atrial natriuretic factor and of the main counteracting sodium-retaining principle, the renin-aldosterone system, in acute volume regulation of cirrhosis of the liver has been investigated. Central volume stimulation was achieved in 21 patients with cirrhosis, 11 without and 10 with ascites, and 25 healthy controls by 1-hr head-out water immersion. Immersion prompted a highly significant (p<0.001) increase of atrial natriuretic factor plasma concentrations in cirrhotic patients without ascites from 8.5 ± 1.3 fmoles per ml to 16.5 ± 2.6 fmoles per ml, comparable to the stimulation in control subjects (6.0 ± 0.6 fmoles per ml to 13.6 ± 2.6 fmoles per ml). In cirrhotic patients with ascites, atrial natriuretic factor increase (from 7.7 ± 1.3 fmoles per ml to 11.4 ± 2.3 fmoles per ml) was blunted (p<0.05). Plasma renin activity and plasma aldosterone concentration were elevated in cirrhotic patients, especially in the presence of ascites. Following immersion, plasma renin activity and plasma aldosterone concentration were reduced similarly in all groups. Water immersion induced a more pronounced natriuresis and diuresis in control subjects than in cirrhotic patients. Neither atrial natriuretic factor nor plasma renin activity nor plasma aldosterone concentration alone correlated to sodium excretion. However, atrial natriuretic factor to plasma aldosterone concentration ratios were closely correlated to basal and stimulated natriuresis in cirrhotic patients, particularly in those with ascites. These data suggest that atrial natriuretic factor and the renin-aldosterone system influence volume regulation in patients with cirrhosis

TIPS for the treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update

Refractory ascites is a frequent complication of advanced cirrhosis and is associated with hepatorenal syndrome and hepatic hydrothorax. Large volume paracentesis and pleurodesis are regarded as first-line treatments in patients who do not respond adequately to diuretics. These treatments, however, do not prevent recurrence and carry the risk of worsening of the circulatory dysfunction leading to hepatorenal syndrome. The transjugular intrahepatic portosystemic shunt ( TIPS) has been proposed as an alternative to paracentesis. TIPS reduces the rate of ascites recurrence mainly due to the reduction in the filtration pressure. In addition, TIPS results in a positive effect on renal function, including hepatorenal syndrome, demonstrated by a rapid increase in urinary sodium excretion, urinary volume, and improvement in plasma creatinine concentration. Furthermore, plasma renin activity, aldosterone, and noradrenalin concentrations improve gradually after TIPS insertion suggesting a positive effect on systemic underfilling, the factor of hepatorenal syndrome. As demonstrated recently in two meta-analyses including five randomised studies, TIPS also improves survival when compared with paracentesis. However, the evidence is based on relatively few studies with only 305 patients included. The positive effects of the TIPS are opposed by an increased frequency and severity of episodes of hepatic encephalopathy which may be reduced by both patient selection and reduced shunt diameter. Based on the present knowledge the recommended hierarchy of treatments for refractory ascites may be reconsidered upgrading TIPS in suitable candidates