Endothelin-1 contributes to maintenance of systemic but not portal haemodynamics in patients with early cirrhosis: a randomised controlled trial.

Abstract

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: D Tripathi, G Therapondos, J W Ferguson, D E Newby, D J Webb, P C Hayes
• Journal: Gut (Gut) Vol. 55 Issue 9 Pg. 1290-5 (Sep 2006) ISSN: 0017-5749 [Print] England
• PMID: 16434427 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Endothelin A Receptor Antagonists
• Endothelin B Receptor Antagonists
• Endothelin-1
• Oligopeptides
• Peptides, Cyclic
• Piperidines
• BQ 788
• cyclo(Trp-Asp-Pro-Val-Leu)

Topics

• Adult
• Aged
• Double-Blind Method
• Endothelin A Receptor Antagonists
• Endothelin B Receptor Antagonists
• Endothelin-1 (blood, physiology)
• Female
• Hemodynamics (drug effects)
• Humans
• Hypertension, Portal (drug therapy, physiopathology)
• Liver Circulation (drug effects)
• Liver Cirrhosis (physiopathology)
• Male
• Middle Aged
• Oligopeptides (adverse effects, pharmacology)
• Peptides, Cyclic (adverse effects, pharmacology)
• Piperidines (adverse effects, pharmacology)
• Pulmonary Circulation (drug effects)