BACKGROUND AND AIMS: Increased endothelin (ET)-1 activity may contribute to the complications of cirrhosis and portal hypertension. The aim of this study was to assess the systemic and portal haemodynamic effects of selective ET-A and ET-B receptor antagonism in patients with cirrhosis. METHODS:Sixteen patients with cirrhosis and portal hypertension (aged 52 (1) years, Pugh score 6.2 (0.3)) underwent 24 studies with infusions of: (A) selective ET-A antagonist, BQ-123 (n = 8), at 1000 and 3000 nmol/min; (B) selective ET-B antagonist, BQ-788 (n = 8), at 100 and 300 nmol/min; or (C) matched saline placebo (n = 8) in a double blind randomised manner. Haemodynamic measurements were performed through pulmonary artery, hepatic venous, and femoral artery catheters. RESULTS: Baseline patient characteristics were well matched. Compared with placebo, BQ-123 decreased mean arterial pressure (MAP -15 (11) mm Hg (-18%); p<0.02) and pulmonary vascular resistance index (PVRI -81 (54) dyn x s x m2/cm5 (-64%); p<0.05), with no effect on hepatic venous pressure gradient (HVPG), cardiac index (CI), or systemic vascular resistance index (SVRI). Compared with placebo, BQ-788 increased MAP (+11 (3) mm Hg (+12%); p<0.03) and SVRI (+1101 (709) dyn x s x m2/cm5 (+50%); p<0.05), reduced CI (-1.0 (0.4) l/min/m2 (-29%); p = 0.05) with no effect on HVPG or PVRI. CONCLUSIONS: ET-1 contributes to maintenance of systemic and pulmonary haemodynamics without acutely affecting HVPG in patients with early cirrhosis. In this group of patients, the use of selective ET-A and ET-B antagonists for the management of variceal haemorrhage is likely to be limited.
RCT Entities:
BACKGROUND AND AIMS: Increased endothelin (ET)-1 activity may contribute to the complications of cirrhosis and portal hypertension. The aim of this study was to assess the systemic and portal haemodynamic effects of selective ET-A and ET-B receptor antagonism in patients with cirrhosis. METHODS: Sixteen patients with cirrhosis and portal hypertension (aged 52 (1) years, Pugh score 6.2 (0.3)) underwent 24 studies with infusions of: (A) selective ET-A antagonist, BQ-123 (n = 8), at 1000 and 3000 nmol/min; (B) selective ET-B antagonist, BQ-788 (n = 8), at 100 and 300 nmol/min; or (C) matched saline placebo (n = 8) in a double blind randomised manner. Haemodynamic measurements were performed through pulmonary artery, hepatic venous, and femoral artery catheters. RESULTS: Baseline patient characteristics were well matched. Compared with placebo, BQ-123 decreased mean arterial pressure (MAP -15 (11) mm Hg (-18%); p<0.02) and pulmonary vascular resistance index (PVRI -81 (54) dyn x s x m2/cm5 (-64%); p<0.05), with no effect on hepatic venous pressure gradient (HVPG), cardiac index (CI), or systemic vascular resistance index (SVRI). Compared with placebo, BQ-788 increased MAP (+11 (3) mm Hg (+12%); p<0.03) and SVRI (+1101 (709) dyn x s x m2/cm5 (+50%); p<0.05), reduced CI (-1.0 (0.4) l/min/m2 (-29%); p = 0.05) with no effect on HVPG or PVRI. CONCLUSIONS: ET-1 contributes to maintenance of systemic and pulmonary haemodynamics without acutely affecting HVPG in patients with early cirrhosis. In this group of patients, the use of selective ET-A and ET-B antagonists for the management of variceal haemorrhage is likely to be limited.
Authors: M C Verhaar; F E Strachan; D E Newby; N L Cruden; H A Koomans; T J Rabelink; D J Webb Journal: Circulation Date: 1998-03-03 Impact factor: 29.690
Authors: Christian M Kähler; Ivo Graziadei; Helene Vogelsinger; Susanna Desole; Katharina Cima; Wolfgang Vogel Journal: Wien Klin Wochenschr Date: 2011-03-31 Impact factor: 1.704
Authors: Dimitris G Tzamouranis; Alexandra Alexopoulou; Spyros P Dourakis; George S Stergiou Journal: BMC Gastroenterol Date: 2010-12-12 Impact factor: 3.067