title: Pulmonary release and coronary and peripheral consumption of big endothelin and endothelin-1 in severe heart failure: acute effects of vasodilator therapy.
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 alpha(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.
authors.affiliation: Medizinische Klinik und Poliklinik, Kardiologie, Charité (Campus Mitte), Humboldt-Universität zu Berlin, Germany. karl.stangl@charite.de
authors.forename: K
authors.initials: K
authors.lastname: Stangl
authors.forename: T
authors.initials: T
authors.lastname: Dschietzig
authors.forename: C
authors.initials: C
authors.lastname: Richter
authors.forename: M
authors.initials: M
authors.lastname: Laule
authors.forename: V
authors.initials: V
authors.lastname: Stangl
authors.forename: E
authors.initials: E
authors.lastname: Tanis
authors.forename: G
authors.initials: G
authors.lastname: Baumann
authors.forename: S B
authors.initials: SB
authors.lastname: Felix
mesh_terms: D000368:Aged; D003326:Coronary Circulation / Q000502:physiology*; D019332:Endothelin-1 / Q000097:blood*; D016232:Endothelins / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D011652:Pulmonary Circulation / Q000502:physiology*; D013318:Stroke Volume; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D010879:Piperazines; D014665:Vasodilator Agents; D009599:Nitroprusside; C015568:urapidil