Pulmonary release and coronary and peripheral consumption of big endothelin and endothelin-1 in severe heart failure - Acute effects of vasodilator therapy

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 alpha(1)-antagonist urapidil (nitric oxid e-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, r espectively, 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 periphe ral 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 pm ol/L]). In these patients, sodium nitroprusside (SNP) and urapidil resulted in comparable hemodynamic improvement after 6 hours (CI: SNP, 63+/-2%; ura pidil, 72+/-3%; PCWP: SNP, -50+/-2%; urapidil, -47+/-2%) and a maximum decr ease in ET peptides by >50%. After 3 hours, pulmonary net release and coron ary 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. S hort-term vasodilator therapy decreases ETs and restores their pulmonary, c oronary, and peripheral balance.