ENDOTHELIN-1 HAS HEMODYNAMIC-EFFECTS AT PATHOPHYSIOLOGICAL CONCENTRATIONS IN PATIENTS WITH LEFT-VENTRICULAR DYSFUNCTION

Objectives: Plasma levels of immunoreactive endothelin-l (ET-1) are ra ised in chronic heart failure. Whether plasma ET-I 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 sys temic vasculature in patients with left ventricular systolic dysfuncti on (LVD), with or without overt heart failure. Methods: ET-1 was infus ed at 1, 5 and 15 pmol/min into a distal pulmonary artery of ten patie nts with LVD to achieve plasma concentrations of ET-1 similar to those found in patients with heart failure and pulmonary hypertension Haemo dynamics were measured using a pulmonary thermodilution catheter and a n arterial line. Intravascular Doppler and local pulmonary angiography were used to assess local pulmonary blood flow in the first four pati ents. Results: Systemic haemodynamic changes occurred with ET-1 infusi on: mean arterial pressure (100+/-3 [standard error of the mean]) to 1 07+/-3 mmHg; p<0.01) and systemic vascular resistance (1699+/-118 to 2 033+/-135 dynes s/cm(5); p<0.001) rose, while the cardiac index fell f rom 2.43+/-0.17 to 2.20+/-0.16 1/min/m(2) (p<0.002). Mean pulmonary ar tery pressure (21+/-2 mmHg) and pulmonary vascular resistance (151+/-1 4 to 147+/-14 dynes s/cm(5)) did not change however. Conclusions: Exog enous ET-1, when infused to achieve plasma concentrations similar to t hose in severe heart failure and pulmonary hypertension, causes system ic but not pulmonary vasoconstriction. (C) 1998 Elsevier Science B.V. All rights reserved.