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

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Abstract

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.

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Cowburn, P. J., Cleland, J. G. F., McArthur, J. D., MacLean, M. R., Dargie, H. J., McMurray, J. J. V., & Morton, J. J. (1998). Endothelin-1 has haemodynamic effects at pathophysiological concentrations in patients with left ventricular dysfunction. Cardiovascular Research, 39(3), 563–570. https://doi.org/10.1016/S0008-6363(98)00084-4

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