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Endothelin-1 contributes to maintenance of systemic but not portal haemodynamics in patients with early cirrhosis: a randomised controlled trial
  1. D Tripathi1,
  2. G Therapondos1,
  3. J W Ferguson1,
  4. D E Newby2,
  5. D J Webb3,
  6. P C Hayes1
  1. 1Department of Hepatology, Royal Infirmary, Edinburgh, UK
  2. 2Department of Cardiology, Royal Infirmary, Edinburgh, UK
  3. 3Centre for Cardiovascular Science, The University of Edinburgh, Western General Hospital, Edinburgh, UK
  1. Correspondence to:
    Dr D Tripathi
    Department of Hepatology, Royal Infirmary, 51 Little France Crescent, Edinburgh EH16 4SU, UK; tdrdhir{at}aol.com

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×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.

  • ET-1, endothelin-1
  • ET-A, endothelin A
  • ET-B, endothelin B
  • MAP, mean arterial pressure
  • PVRI, pulmonary vascular resistance index
  • HR, heart rate
  • SVRI, systemic vascular resistance index
  • HSC, hepatic stellate cell
  • HVPG, hepatic venous pressure gradient
  • FHVP, free hepatic venous pressure
  • WHVP, wedged hepatic venous pressure
  • PAP, pulmonary artery pressure
  • PAWP, pulmonary artery wedged pressure
  • MPAP, mean pulmonary artery pressure
  • RAP, right atrial pressure
  • CO, cardiac output
  • CI, cardiac index
  • HBF, hepatic blood flow
  • ICG, indocyanine green
  • PPHT, portopulmonary hypertension
  • endothelin-1
  • portal hypertension
  • hepatic venous pressure gradient
  • cirrhosis

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Footnotes

  • Published online first 24 January 2006

  • Conflict of interest: None declared.

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