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

Tripathi, D.; Therapondos, G.; Ferguson, J. W.; Newby, D. E.; Webb, D. J.; Hayes, P. C.
September 2006
Gut;Sep2006, Vol. 55 Issue 9, p1290
Academic Journal
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 (Cl), 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 Cl (-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.


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