RT Journal Article
SR Electronic
T1 Endothelin-1 contributes to maintenance of systemic but not portal haemodynamics in patients with early cirrhosis: a randomised controlled trial
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1290
OP 1295
DO 10.1136/gut.2005.077453
VO 55
IS 9
A1 D Tripathi
A1 G Therapondos
A1 J W Ferguson
A1 D E Newby
A1 D J Webb
A1 P C Hayes
YR 2006
UL http://gut.bmj.com/content/55/9/1290.abstract
AB 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×s×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×s×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.