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Endothelial function
Inhomogeneous vasomotor effects of moderate selective and non-selective endothelin-receptor blockade in stable coronary artery disease
  1. P Wexberg1,
  2. W Sperker1,
  3. N G Morgenthaler2,
  4. H Heinzl3,
  5. C Adlbrecht1,
  6. C Plass1,
  7. H D Glogar1,
  8. I M Lang1,
  9. T Neunteufl1
  1. 1
    Department of Cardiology, Division of Internal Medicine II, Medical University of Vienna, Vienna, Austria
  2. 2
    Research Department, Brahms AG, Biotechnology Centre Hennigsdorf/Berlin, Germany
  3. 3
    Core Unit for Medical Statistics and Informatics, Medical University of Vienna, Vienna, Austria
  1. Professor Paul Wexberg, Department of Cardiology, Division of Internal Medicine II, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria; paul.wexberg{at}wienkav.at

Abstract

Objective: To explore the morphological and functional effect of selective and non-selective endothelin (ET)-receptor blockade in coronary artery disease (CAD).

Design: Prospective randomised controlled trial.

Setting: University hospital.

Patients: 26 patients with stable CAD.

Interventions: 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.

Main outcome measures: 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.

Trial registration number: NCT00427232.

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Footnotes

  • Funding: This study has been supported by a grant of the Austrian Society of Cardiology.

  • Competing interests: None.

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