(Circulation. 2000;102:1132.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Pulmonary Release and Coronary and Peripheral Consumption of Big Endothelin and Endothelin-1 in Severe Heart Failure
Acute Effects of Vasodilator Therapy
From the Medizinische Klinik und Poliklinik, Kardiologie, Charité (Campus Mitte), Humboldt-Universität zu Berlin, Germany. Dr Felix is currently affiliated with the Klinik Innere Medizin B, Universität Greifswald.
Correspondence to Karl Stangl, MD, Medizinische Klinik und Poliklinik, mit Schwerpunkt Kardiologie, Angiologie und Pulmologie, Charité (Campus Mitte), Humboldt-Universität zu Berlin, Schumannstraße 20/21, 10098 Berlin, Germany. E-mail karl.stangl{at}charite.de
Background—We investigated plasma endothelin (ET) levels in patients with congestive heart failure (CHF) during treatment for acute decompensation; we also measured imbalances in ET peptides across the pulmonary, coronary, and peripheral circulation.
Methods and Results—In patients with severe CHF (n=21; cardiac
index [CI], 1.9±0.2 L · min-1 ·
m-2; pulmonary capillary wedge pressure
[PCWP], 31±1 mm Hg), vasodilation was achieved with the nitric
oxide donor sodium nitroprusside (n=11) or with the
1-antagonist urapidil (nitric
oxide–independent, n=10). ET concentrations were determined from
arterial blood and blood from the pulmonary
artery, coronary sinus, and antecubital vein. Depending
on sites of measurement, baseline big ET and ET-1 levels were,
respectively, 12 to 16 times and 5 to 11 times higher than in controls
(n=11), and 4 to 6 times and 2 to 3 times higher than in patients with
moderate CHF (n=10; CI, 2.7±0.3 L · min-1 ·
m-2; PCWP, 14±2 mm Hg). Patients with severe CHF
demonstrated pulmonary net release and coronary and
peripheral net consumption of both peptides (ie,
arterial levels [big ET, 7.3±1.3 pmol/L; ET-1, 1.8±0.1
pmol/L] were higher than levels in the pulmonary artery
[6.7±1.2 pmol/L; 1.3±0.1 pmol/L], coronary sinus [6.4±1.0
pmol/L; 1.4±0.1 pmol/L], and antecubital vein [6.6±1.1 pmol/L;
1.3±0.1 pmol/L]). In these patients, sodium nitroprusside (SNP) and
urapidil resulted in comparable hemodynamic improvement
after 6 hours (CI: SNP, 63±2%; urapidil, 72±3%; PCWP: SNP,
-50±2%; urapidil, -47±2%) and a maximum decrease in ET
peptides by >50%. After 3 hours, pulmonary net release and
coronary and peripheral net consumption were no
longer detectable.
Conclusions—In patients with severe CHF, the lungs act as a producer and the heart and the periphery act as consumers of elevated circulating ETs. Short-term vasodilator therapy decreases ETs and restores their pulmonary, coronary, and peripheral balance.
Key Words: heart failure • endothelin • lung • hemodynamics
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