title: Pulmonary and systemic responses to exogenous endothelin-1 in patients with left ventricular dysfunction.
abstract: Plasma levels of immunoreactive endothelin-1 (ET-1) are elevated in chronic heart failure (CHF) and have been reported to correlate closely with pulmonary hemodynamic measurements. We investigated the effects of exogenous ET-1 on the pulmonary vasculature in patients with left ventricular systolic dysfunction (LVD), with or without overt heart failure. ET-1 was infused at 1, 5, and 15 pmol/min into a distal pulmonary artery of 10 patients with LVD. Hemodynamics were measured by a thermodilution catheter and arterial line. Intravascular Doppler and local pulmonary angiography were used to assess local pulmonary blood flow in the first four patients. Systemic hemodynamic changes occurred with ET-1 infusion in a dose-dependent fashion. Mean arterial pressure (100 +/- 8-107 +/- 11 mm Hg; p < 0.01) and systemic vascular resistance (1,699 +/- 375-2,033 +/- 427 dynes/s/cm-5; p < 0.001) rose, whereas the cardiac index fell from 2.43 +/- 0.53 to 2.20 +/- 0.491/min/m2 (p < 0.002). However, mean pulmonary artery pressure (21 +/- 7 mm Hg) and pulmonary vascular resistance (151 +/- 43-147 +/- 43 dynes/s/cm-5) did not change. Exogenous ET-1, when infused into patients with LVD, causes systemic but not pulmonary vasoconstriction.
authors.affiliation: Medical Research Council Clinical Research Initiative in Heart Failure, University of Glasgow, Scotland.
authors.forename: P J
authors.initials: PJ
authors.lastname: Cowburn
authors.forename: J G
authors.initials: JG
authors.lastname: Cleland
authors.forename: J D
authors.initials: JD
authors.lastname: McArthur
authors.forename: M R
authors.initials: MR
authors.lastname: MacLean
authors.forename: J J
authors.initials: JJ
authors.lastname: McMurray
authors.forename: H J
authors.initials: HJ
authors.lastname: Dargie
mesh_terms: D000368:Aged; D000792:Angiography; D019332:Endothelin-1 / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*
chemical_list: D019332:Endothelin-1; D009599:Nitroprusside