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Cardiovascular Research 1998 39(3):563-570; doi:10.1016/S0008-6363(98)00084-4
© 1998 by European Society of Cardiology
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Copyright © 1998, European Society of Cardiology

Endothelin-1 has haemodynamic effects at pathophysiological concentrations in patients with left ventricular dysfunction

Peter J. Cowburna,b, John G.F. Clelanda,b,*, John D. McArthurb, Margaret R. MacLeana, Henry J. Dargiea,b, John J.V. McMurraya,b and James J. Mortona

aMedical Research Council Clinical Research Initiative in Heart Failure, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
bDepartment of Cardiology, Western Infirmary, Glasgow G11 6NT, Scotland, UK

* Corresponding author. Tel.: +44 (141) 330 6151; Fax: +44 (141) 330 6151; E-mail: J.Cleland@bio.gla.ac.uk

Objectives: Plasma levels of immunoreactive endothelin-1 (ET-1) are raised in chronic heart failure. Whether plasma ET-1 contributes to the haemodynamic derangement found in chronic heart failure is not known. We investigated the effects of exogenous ET-1 on the pulmonary and systemic vasculature in patients with left ventricular systolic dysfunction (LVD), with or without overt heart failure. Methods: ET-1 was infused at 1, 5 and 15 pmol/min into a distal pulmonary artery of ten patients with LVD to achieve plasma concentrations of ET-1 similar to those found in patients with heart failure and pulmonary hypertension. Haemodynamics were measured using a pulmonary thermodilution catheter and an arterial line. Intravascular Doppler and local pulmonary angiography were used to assess local pulmonary blood flow in the first four patients. Results: Systemic haemodynamic changes occurred with ET-1 infusion: mean arterial pressure (100±3 [standard error of the mean]) to 107±3 mmHg; p<0.01) and systemic vascular resistance (1699±118 to 2033±135 dynes s/cm5; p<0.001) rose, while the cardiac index fell from 2.43±0.17 to 2.20±0.16 l/min/m2 (p<0.002). Mean pulmonary artery pressure (21±2 mmHg) and pulmonary vascular resistance (151±14 to 147±14 dynes s/cm5) did not change however. Conclusions: Exogenous ET-1, when infused to achieve plasma concentrations similar to those in severe heart failure and pulmonary hypertension, causes systemic but not pulmonary vasoconstriction.

KEYWORDS Endothelin; Heart failure; Left ventricular dysfunction


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