This Article Full Text Full Text (PDF) All Versions of this Article: 106/13/1618    most recent 01.CIR.0000034444.31846.F4v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ooi, H. Articles by Givertz, M. M. Search for Related Content PubMed PubMed Citation Articles by Ooi, H. Articles by Givertz, M. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Heart Failure Pulmonary Hypertension Hazardous Substances DB THIOPHENE Related Collections Congestive Pulmonary circulation and disease

(Circulation. 2002;106:1618.)
© 2002 American Heart Association, Inc.

Brief Rapid Communications

Endothelin Mediates Increased Pulmonary Vascular Tone in Patients With Heart Failure

Demonstration by Direct Intrapulmonary Infusion of Sitaxsentan

From the Cardiovascular Section, Department of Medicine and the Cardiomyopathy Program, Boston University School of Medicine, Boston, Mass. Dr Givertz is currently at the Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass.

Correspondence to Wilson S. Colucci, MD, Boston University Medical Center, 88 East Newton St, Boston, MA 02118. E-mail wilson.colucci{at}bmc.org

Background— In patients with chronic heart failure (HF), the pulmonary circulation is a major source of endothelin-1 (ET), and ET levels correlate with pulmonary vascular resistance (PVR). The role of ET in causing pulmonary vasoconstriction in HF is not known, however, in part because of the confounding effects of ET receptor antagonists on systemic hemodynamics.

Methods and Results— To directly test the hypothesis that ET causes pulmonary vasoconstriction in patients with HF, we infused the selective ET_A receptor antagonist sitaxsentan at increasing rates (0.3125 to 10 mg/min) into a left lower-lobe segmental pulmonary artery in 8 patients with left ventricular (LV) systolic failure (LV ejection fraction, 24±4%) and 4 control subjects with normal LV function. Changes in local PVR distal to the infusion site were assessed by measuring the change in pulmonary blood flow velocity with a Doppler-tipped wire and the mean pulmonary artery pressure (MPAP). Total PVR at baseline was elevated in HF patients (177±23 dyne · s · cm^-5) versus controls (89±21 dyne · s · cm^-5; P<0.05). In patients with HF, sitaxsentan caused an infusion rate–dependent decrease in local PVR (P<0.05 versus baseline; P<0.05 versus controls). In contrast, sitaxsentan infusion had no effect on local PVR in controls. Heart rate, mean arterial pressure, cardiac index, and MPAP were not affected by sitaxsentan in either group.

Conclusion— Selective ET_A receptor blockade caused local pulmonary vasodilation in patients with HF, but not in control subjects with normal LV function. These data indicate that ET contributes to the secondary pulmonary hypertension associated with HF.

Key Words: endothelin • heart failure • hypertension, pulmonary

This article has been cited by other articles:

				V. Faoro, S. Boldingh, M. Moreels, S. Martinez, M. Lamotte, P. Unger, S. Brimioulle, S. Huez, and R. Naeije Bosentan Decreases Pulmonary Vascular Resistance and Improves Exercise Capacity in Acute Hypoxia Chest, May 1, 2009; 135(5): 1215 - 1222. [Abstract] [Full Text] [PDF]

				L. Ray, M. Mathieu, P. Jespers, I. Hadad, M. Mahmoudabady, A. Pensis, S. Motte, I. R. Peters, R. Naeije, and K. McEntee Early increase in pulmonary vascular reactivity with overexpression of endothelin-1 and vascular endothelial growth factor in canine experimental heart failure Exp Physiol, March 1, 2008; 93(3): 434 - 442. [Abstract] [Full Text] [PDF]

				J. G.F. Cleland, A. P. Coletta, M. Lammiman, K. K. Witte, H. Loh, M. Nasir, and A. L. Clark Clinical trials update from the European Society of Cardiology meeting 2005: CARE-HF extension study, ESSENTIAL, CIBIS-III, S-ICD, ISSUE-2, STRIDE-2, SOFA, IMAGINE, PREAMI, SIRIUS-II and ACTIVE Eur J Heart Fail, October 1, 2005; 7(6): 1070 - 1075. [Abstract] [Full Text] [PDF]