title: Left main coronary arterial endothelial function and heterogenous segmental epicardial vasomotor reactivity in vivo: novel insights with intravascular ultrasonography.
abstract: OBJECTIVE
  While the relationship between epicardial coronary vasomotor reactivity and cardiovascular events is well established, this observation has yet to be evaluated within the left main coronary artery (LMCA) in humans in vivo. Our aims were to test the endothelium-dependent vasomotor properties of the LMCA, and to compare these responses to downstream epicardial segments.
  
  
  RESULTS
  Thirty patients referred for coronary angiography underwent intracoronary (IC) salbutamol provocation during intravascular ultrasound imaging within a non-critically diseased, left-sided conduit vessel. Macrovascular vasomotor response [change in average lumen area (LA) at baseline and following 5 min of 0.30 µg/min IC salbutamol] and percent atheroma volume (PAV) were evaluated in 30 LMCA, 42 proximal, 109 mid, and 132 distal epicardial coronary segments. In comparison with all other segments, the LMCA had the greatest lumen and vessel areas (P < 0.001), yet the proximal epicardial segments contained the greatest PAV (P < 0.02). The mid and distal epicardial segments displayed significant endothelium-dependent vasodilatation from baseline (P = 0.017 and <0.001, respectively); however, the proximal epicardial and LMCA segments did not (P = 0.45 and 0.16, respectively). Significant segmental vasomotor heterogeneity was noted in all 30 patients, with opposing vasomotor responses between adjacent LMCA and epicardial segments. Across all segments, baseline LA inversely correlated with the % change in LA (r = -0.16, P = 0.0005).
  
  
  CONCLUSIONS
  Endothelium-dependent vasomotor reactivity is heterogenous within the conduit coronary system. Vascular dynamic responses were less prominent in the larger calibre LMCA and proximal epicardial segments. This may, in part, relate to higher shear stress in smaller, distal segments and yet also may explain the propensity for culprit plaques to cluster proximally.
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, Australia Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA C5Research, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Rishi
authors.initials: R
authors.lastname: Puri
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia Cardiovascular Investigation Unit, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.affiliation: C5Research, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Brennan
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
authors.forename: Jordan
authors.initials: J
authors.lastname: Andrews
authors.affiliation: C5Research, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Karilane L
authors.initials: KL
authors.lastname: King
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Gary Y
authors.initials: GY
authors.lastname: Liew
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Angelo
authors.initials: A
authors.lastname: Carbone
authors.affiliation: Cardiovascular Investigation Unit, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Copus
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Nelson
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Samir R
authors.initials: SR
authors.lastname: Kapadia
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Emin Murat
authors.initials: EM
authors.lastname: Tuzcu
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Beltrame
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, Australia Cardiovascular Investigation Unit, Royal Adelaide Hospital, Adelaide, Australia Department of Medicine, Cardiovascular Research Centre, Royal Adelaide Hospital, Level 6, Theatre Block, North Terrace, Adelaide, SA 5000, Australia.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Worthley
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, Australia Cardiovascular Investigation Unit, Royal Adelaide Hospital, Adelaide, Australia Department of Medicine, Cardiovascular Research Centre, Royal Adelaide Hospital, Level 6, Theatre Block, North Terrace, Adelaide, SA 5000, Australia matthew.worthley@adelaide.edu.au.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Worthley
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging*; D018084:Ultrasonography, Interventional; D014664:Vasodilation
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D015415:Biomarkers; D000420:Albuterol
keywords: Endothelial function; IVUS; Left main coronary artery; Salbutamol