© 2001 European Society of Cardiology
Tezosentan (an intravenous endothelin receptor A/B antagonist) reduces peripheral resistance and increases cardiac power therefore preventing a steep decrease in blood pressure in patients with congestive heart failure
a The Cardiology Institute, Assaf-Harofeh Medical Center 70300 Zerifin, Israel
b The Division of Cardiology, University Hospital Zurich, Switzerland
c Actelion Ltd Allschwil, Switzerland
d Rebecca Sieff Government Hospital Safed, Israel
e Ashkelon Hospital Ashkelon, Israel
f Kaplan Hospital Kaplan, Israel
* Corresponding author. Tel.: +972-8-977-9778; fax: +972-8-977-9779.
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Abstract |
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Objective: This study investigated the effect of tezosentan (an intravenous endothelin-1 receptor antagonist) on vascular resistance and cardiac function and determined the dose response in patients with stable congestive heart failure (CHF) due to left ventricular systolic dysfunction.
Methods: In a double-blind fashion, tezosentan or placebo were administered in ascending doses (5, 20, 50, 100 mg h–1) to 38 CHF (NYHA class III) patients with ejection fraction 
35%, cardiac index 2.7 l min–1 m–2 and pulmonary capillary wedge pressure 
15 mmHg. Systemic vascular resistance index (SVRi) was estimated as mean arterial blood pressure [(MAP-right atrial pressure)÷cardiac index (CI)]. Cardiac function was assessed as cardiac power index (Cpi), calculated as pressure x flow (MAP x CI), where MAP represents pressure and CI represents cardiovascular flow.
Results and discussion: Compared to the placebo, tezosentan induced a dose-dependent decrease in SVRi (–32%), an increase in Cpi (+20%) and a small decrease in MAP (–9%). By contrast, patients treated with nitrate vasodilators or nesiritide (a natriuretic peptide) showed a decrease in SVRi not accompanied by a significant increase in Cpi leading to a steep decrease in MAP.
Conclusions: The use of Cpi in the assessment of the hemodynamic effects of tezosentan, provides a useful alternative characterization of the complex influences of vasodilators on cardiac function in patients with CHF.
Key Words: Tezosentan • Blood pressure • Congestive heart failure
Received December 15, 2000; Revised March 19, 2001; Accepted May 10, 2001
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