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.
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.


CONCLUSIONS
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.
Cotter
G
G
The Cardiology Institute, Assaf-Harofeh Medical Center, 70300 Zerifin, Israel.
Kiowski
W
W
Kaluski
E
E
Kobrin
I
I
Milovanov
O
O
Marmor
A
A
Jafari
J
J
Reisin
L
L
Krakover
R
R
Vered
Z
Z
Caspi
A
A
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D065128:Endothelin Receptor Antagonists; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006334:Heart Function Tests; D006801:Humans; D007022:Hypotension / Q000517:prevention & control*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011336:Probability; D011725:Pyridines / Q000008:administration & dosage*; D017466:Receptors, Endothelin / Q000008:administration & dosage; D012016:Reference Values; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D017466:Receptors, Endothelin; D013777:Tetrazoles; C120582:tezosentan