Inhomogeneous vasomotor effects of moderate selective and non-selective endothelin-receptor blockade in stable coronary artery disease.
OBJECTIVE
To explore the morphological and functional effect of selective and non-selective endothelin (ET)-receptor blockade in coronary artery disease (CAD).


METHODS
Prospective randomised controlled trial.


METHODS
University hospital.


METHODS
26 patients with stable CAD.


METHODS
Intracoronary infusion (30 minutes) of the ET-A receptor blocker BQ-123 (40 nmol/min, group A, n = 13) alone or with the ET-B receptor blocker BQ-788 (10 nmol/min, group AB, n = 13) as well.


METHODS
Fractional flow reserve (FFR), coronary flow reserve (CFR) and intramyocardial resistance (IMR) by PressureWire, mean arterial blood pressure (MAP), minimal lumen diameter (MLD) and average angiographic lumen diameter (mean LD) of the target vessel before and after intracoronary infusion of ET antagonists. Concentrations of C-terminal pro-endothelin-1 (CT-proET1) in arterial blood were determined before and after infusion.


RESULTS
Mean MLD, mean LD, FFR, CFR, IMR and MAP remained unaffected by ET-receptor blockade in both groups; their changes were comparable. Concentrations of CT-proET-1 increased by 6.2 (SD 5.9) pmol/l (95% CI 1.2 to 11.1 pmol/l; p = 0.022) in group A and by 4.1 (SD 4.3) pmol/l (95% CI 1.1 to 7.2 pmol/l; p = 0.014) in group AB.


CONCLUSIONS
We found a broad variety of individual haemodynamic responses to ET-receptor antagonists with an overall neutral effect after an infusion period of 30 minutes despite an overall effective blockade of ET-receptors. Prolonged infusion time may be needed to cause a more distinct vasomotor response.


BACKGROUND
NCT00427232.
Wexberg
P
P
Department of Cardiology, Division of Internal Medicine II, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. paul.wexberg@wienkav.at
Sperker
W
W
Morgenthaler
N G
NG
Heinzl
H
H
Adlbrecht
C
C
Plass
C
C
Glogar
H D
HD
Lang
I M
IM
Neunteufl
T
T
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy / Q000503:physiopathology; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D053805:Fractional Flow Reserve, Myocardial / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology; D009842:Oligopeptides / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D055815:Young Adult
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D011498:Protein Precursors; C093240:proendothelin 1; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)