Document Detail

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.
MedLine Citation:
PMID:  11511432     Owner:  NLM     Status:  MEDLINE    
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 <or=35%, cardiac index <or=2.7 l min(-1) m(-2) and pulmonary capillary wedge pressure >or=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.
G Cotter; W Kiowski; E Kaluski; I Kobrin; O Milovanov; A Marmor; J Jafari; L Reisin; R Krakover; Z Vered; A Caspi
Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial    
Journal Detail:
Title:  European journal of heart failure     Volume:  3     ISSN:  1388-9842     ISO Abbreviation:  Eur. J. Heart Fail.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-20     Completed Date:  2001-10-18     Revised Date:  2011-06-08    
Medline Journal Info:
Nlm Unique ID:  100887595     Medline TA:  Eur J Heart Fail     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  457-61     Citation Subset:  IM    
The Cardiology Institute, Assaf-Harofeh Medical Center, 70300 Zerifin, Israel.
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MeSH Terms
Blood Pressure / drug effects
Confidence Intervals
Dose-Response Relationship, Drug
Double-Blind Method
Follow-Up Studies
Heart Failure / complications,  diagnosis,  drug therapy*
Heart Function Tests
Hypotension / prevention & control*
Infusions, Intravenous
Middle Aged
Pyridines / administration & dosage*
Receptors, Endothelin / administration & dosage,  antagonists & inhibitors*
Reference Values
Severity of Illness Index
Stroke Volume / drug effects
Tetrazoles / administration & dosage*
Treatment Outcome
Vascular Resistance / drug effects
Reg. No./Substance:
0/Pyridines; 0/Receptors, Endothelin; 0/Tetrazoles; 0/tezosentan

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