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Inhomogenous vasomotoric effects of moderate selective and non-selective endothelin-receptor blockade in stable coronary artery disease
  1. Paul Wexberg (paul.wexberg{at}wienkav.at)
  1. Medical University of Vienna, Austria
    1. Wolfgang Sperker (wolfgang.sperker{at}gmx.at)
    1. Medical University of Vienna, Austria
      1. Nils G Morgenthaler (n.morgenthaler{at}brahms.de)
      1. BRAHMS AG, Germany
        1. Harald Heinzl (harald.heinzl{at}meduniwien.ac.at)
        1. Medical University of Vienna, Austria
          1. Christopher Adlbrecht (christopher.adlbrecht{at}meduniwien.ac.at)
          1. Medical University of Vienna, Austria
            1. Christian Plass (christian.plass{at}meduniwien.ac.at)
            1. Medical University of Vienna, Austria
              1. Helmut D Glogar (helmut-dietmar.glogar{at}meduniwien.ac.at)
              1. Medical University of Vienna, Austria
                1. Irene Lang (irene.lang{at}meduniwien.ac.at)
                1. University Hospital Vienna, Austria
                  1. Thomas Neunteufl (thomas.neunteufl{at}meduniwien.ac.at)
                  1. Medical University of Vienna, Austria

                    Abstract

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

                    Design: Prospective randomized controlled trial.

                    Setting: University hospital.

                    Patients: 26 patients with stable CAD.

                    Interventions: intracoronary infusion (30 minutes) of the ET-A receptor blocker BQ-123 (40nmol/min, Group A, n=13) alone or with the ET-B receptor blocker BQ-788 (10nmol/min, Group AB, n=13) on top.

                    Main outcome measures: Fractional flow reserve (FFR), coronary flow reserve (CFR) and intramyocardial resistance (IMR) by Pressure Wire, mean arterial blood pressure (MAP), minimal (MLD) and average angiographic lumen diameter (nsMLD) 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, nsMLD, 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 ± 5.9 pmol/l (95% CI 1.2 – 11.1 pmol/l; p=0.022) in group A and by 4.1 ± 4.3 pmol/l (95% CI 1.1 – 7.2 pmol/l; p=0.014) in group AB.

                    Conclusions: We found a broad variety of individual hemodynamic responses to ET-receptor antagonists with an overall neutral effect after an infusion period of thirty minutes despite an overall effective blockade of ET-receptors . Prolonged infusion time may be needet to cause a more distinct vasomotoric response.

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