Pulmonary Release and Coronary and Peripheral Consumption of Big Endothelin and Endothelin-1 in Severe Heart Failure

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Abstract
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 α1-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.