Endothelin-1 has haemodynamic effects at pathophysiological concentrations in patients with left ventricular dysfunction.
OBJECTIVE
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.
Cowburn
P J
PJ
Medical Research Council Clinical Research Initiative in Heart Failure, University of Glasgow, Scotland, UK.
Cleland
J G
JG
McArthur
J D
JD
MacLean
M R
MR
Dargie
H J
HJ
McMurray
J J
JJ
Morton
J J
JJ
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D011651:Pulmonary Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D011859:Radiography; D012039:Regional Blood Flow / Q000187:drug effects; D018084:Ultrasonography, Interventional; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000097:blood / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000503:physiopathology*
D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside