title: Role of endothelin in microvascular dysfunction following percutaneous coronary intervention for non-ST elevation acute coronary syndromes: a single-centre randomised controlled trial.
abstract: Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1 (ET-1) is a potent vasoconstrictor, and its expression is increased in atherosclerosis and after PCI. In this study, we aim to define the role of endothelin in regulating coronary microvascular blood flow and myocardial perfusion following PCI in patients with non-ST elevation acute coronary syndromes (NSTACS), by assessing whether adjunctive therapy with a selective endothelin A (ETA) receptor antagonist acutely improves postprocedural coronary microvascular blood flow.
  
  
  
  In a randomised, double-blinded, placebo-controlled trial, 23 NSTACS patients were enrolled to receive an intracoronary infusion of placebo (n=11) or BQ-123 (n=12) immediately before PCI. Post-PCI coronary microvascular blood flow and myocardial perfusion were assessed by measuring Doppler-derived average peak velocity (APV), and cardiac biomarker levels were quantified.
  
  
  
  Compared with the placebo group, APV was significantly higher in the drug group immediately after PCI (30 (20, 37) vs 19 (9, 26) cm/s; p=0.03). Hyperaemic APV, measured post-adenosine administration, was higher in the BQ-123 group, but the difference did not achieve statistical significance (56 (48, 72) vs 46 (34, 64) cm/s; p=0.090). Maximum coronary flow reserve postprocedure was not different between the two groups (2.1 (1.6, 2.3) vs 2.5 (1.8, 3.0)). Per cent change in creatine kinase isoenzyme MB from the time of PCI to 8 and 16 hours post-PCI was significantly lower in the drug group compared with the placebo group (-17 (-26, -10) vs 26 (-15, 134); p=0.02 and -17 (-38, 14) vs 107 (2, 446); p=0.007, respectively).
  
  
  
  Endothelin is a mediator of microvascular dysfunction during PCI in NSTACS, and adjunctive selective ETA antagonist may augment myocardial perfusion during PCI.
  
  
  
  NCT00586820; Results.
authors.affiliation: Division of Cardiovascular Diseases, Mayo College of Medicine, Rochester, Minnesota, USA; Division of Internal Medicine, Marshfield Clinic, Marshfield, Wisconsin, USA.
authors.forename: Raviteja R
authors.initials: RR
authors.lastname: Guddeti
authors.affiliation: Division of Cardiovascular Diseases , Mayo College of Medicine , Rochester, Minnesota , USA.
authors.forename: Abhiram
authors.initials: A
authors.lastname: Prasad
authors.affiliation: Division of Cardiovascular Diseases , Mayo College of Medicine , Rochester, Minnesota , USA.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzawa
authors.affiliation: Division of Cardiovascular Diseases , Mayo College of Medicine , Rochester, Minnesota , USA.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Division of Cardiovascular Diseases , Mayo College of Medicine , Rochester, Minnesota , USA.
authors.forename: Charanjit
authors.initials: C
authors.lastname: Rihal
authors.affiliation: Division of Cardiovascular Diseases , Mayo College of Medicine , Rochester, Minnesota , USA.
authors.forename: David
authors.initials: D
authors.lastname: Holmes
authors.affiliation: Division of Cardiovascular Diseases , Mayo College of Medicine , Rochester, Minnesota , USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Best
authors.affiliation: Division of Biomedical Statistics and Informatics , Mayo College of Medicine , Rochester, Minnesota , USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Lennon
authors.affiliation: Division of Nephrology and Hypertension , Mayo Clinic , Rochester, Minnesota , USA.
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.affiliation: Division of Cardiovascular Diseases , Mayo College of Medicine , Rochester, Minnesota , USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman