INCREASED PLASMA ENDOTHELIN IN CIRRHOSIS - RELATIONSHIP WITH SYSTEMICENDOTOXEMIA AND RESPONSE TO CHANGES IN EFFECTIVE BLOOD-VOLUME

Background/Aims: Patients with cirrhosis and ascites show high plasma concentrations of endothelin. The aim of the current study was to inve stigate whether this feature is a compensatory response to effective h ypovolemia or a consequence of systemic endotoxemia. Methods:Protocols 1 and 2 assess the effect of acute changes in effective blood volume on plasma endothelin, and protocol 3 investigates the relationship bet ween plasma endotoxin and endothelin in patients with cirrhosis and as cites. Protocol 1 included nine healthy subjects and 26 patients with cirrhosis studied during supine rest, upright tilt (which decreases ef fective blood volume) and cycloergometric exercise (which activates va soactive systems by a baroreceptor independent mechanism). Protocol 2 included six patients studied before and 1 and 3 h after the intraveno us administration of a plasma expander. In protocol 3, the plasma leve ls of endothelin and endotoxin were measured in 17 non-infected patien ts with cirrhosis and also in four patients with spontaneous bacterial peritonitis at diagnosis and following resolution of infection. Resul ts: Plasma endothelin was 3-5 times higher in patients with cirrhosis than in healthy volunteers, In healthy subjects, upright tilt and exer cise were associated with a significant activation of the renin-aldost erone and sympathetic nervous systems and an increase in plasma endoth elin, In patients with cirrhosis, upright tilt and exercise were assoc iated with a significant increase and plasma volume expansion with a m arked supression of the renin-aldosterone and sympathetic nervous syst ems, However, in these patients none of these maneuvers affected plasm a endothelin levels, In the patients with cirrhosis in protocol 3, the re was no correlation between plasma endotoxin and endothelin, Resolut ion of peritonitis was associated with a marked fall in plasma endotox in and no changes in plasma endothelin, Conclusions: These findings su ggest that mechanisms other than effective hypovolemia or systemic end otoxemia are involved in the increased plasma endothelin of cirrhosis with ascites.