Document Detail

Endothelin-1 contributes to maintenance of systemic but not portal haemodynamics in patients with early cirrhosis: a randomised controlled trial.
MedLine Citation:
PMID:  16434427     Owner:  NLM     Status:  MEDLINE    
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.
D Tripathi; G Therapondos; J W Ferguson; D E Newby; D J Webb; P C Hayes
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial     Date:  2006-01-24
Journal Detail:
Title:  Gut     Volume:  55     ISSN:  0017-5749     ISO Abbreviation:  Gut     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-14     Completed Date:  2006-09-21     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  England    
Other Details:
Languages:  eng     Pagination:  1290-5     Citation Subset:  AIM; IM    
Department of Hepatology, Royal Infirmary, 51 Little France Crescent, Edinburgh EH16 4SU, UK.
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MeSH Terms
Double-Blind Method
Endothelin-1 / blood,  physiology*
Hemodynamics* / drug effects
Hypertension, Portal / drug therapy,  physiopathology*
Liver Circulation / drug effects
Liver Cirrhosis / physiopathology*
Middle Aged
Oligopeptides / adverse effects,  pharmacology
Peptides, Cyclic / adverse effects,  pharmacology
Piperidines / adverse effects,  pharmacology
Pulmonary Circulation / drug effects
Receptor, Endothelin A / antagonists & inhibitors
Receptor, Endothelin B / antagonists & inhibitors
Reg. No./Substance:
0/BQ 788; 0/Endothelin-1; 0/Oligopeptides; 0/Peptides, Cyclic; 0/Piperidines; 0/Receptor, Endothelin A; 0/Receptor, Endothelin B; 136553-81-6/cyclo(Trp-Asp-Pro-Val-Leu)
Comment In:
Gut. 2006 Sep;55(9):1230-2   [PMID:  16905694 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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