title: Widespread endotheliopathy in adults with cyanotic congenital heart disease.
abstract: BACKGROUND
  Cyanotic congenital heart disease is associated with functional limitation and vascular events. The nature and extent of endothelial dysfunction in cyanotic adults is poorly understood. We sought to characterise endothelial function in this setting.
  
  
  METHODS
  A total of fourteen adults with cyanotic congenital heart disease (40±3 years) together with age- and sex-matched healthy controls underwent assessment of nitric oxide-dependent vascular responses, including flow-mediated dilatation of the brachial artery and dynamic vessel analysis of the retina in response to flickering light. Plasma levels of the endothelium-derived vasoconstrictor endothelin-1 and the nitric oxide antagonist, asymmetric dimethylarginine, were measured. Circulating endothelial progenitor cells were assessed by flow cytometry.
  
  
  RESULTS
  Flow-mediated dilatation was significantly lower in cyanosed adults than controls (4.0±0.8 versus 7.2±1.0%, p=0.019, n=11 per group). Retinal arterial and venous dilatory responses were also impaired (2.9±0.8 versus 5.0±0.6%, p=0.05 and 3.4±0.3 versus 5.2±0.7%, p=0.04, n=13). Serum levels of endothelin-1 and asymmetric dimethylarginine were higher in cyanosed adults (3.0±0.6 versus 1.1±0.1 pg/ml, p=0.004 and 0.68±0.05 versus 0.52±0.02 μmol/L, p=0.03, n=11). Endothelial progenitor cells (CD34+CD45dimCD133+KDR+) were reduced in those with chronic cyanosis (17±4 versus 40±6 per million white blood cells, p=0.005, n=11).
  
  
  CONCLUSIONS
  Endothelial function is impaired in the systemic arteries and retinal vessels in adults with cyanotic congenital heart disease, suggesting a widespread endotheliopathy. Diminished numbers of endothelial progenitor cells might potentially contribute to these observations.
authors.affiliation: 1Department of Cardiology,Royal Prince Alfred Hospital,Sydney,Australia.
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Cordina
authors.affiliation: 3Heart Research Institute,Sydney,Australia.
authors.forename: Shirley
authors.initials: S
authors.lastname: Nakhla
authors.affiliation: 2Department of Cardiology,Sydney Medical School,Sydney,Australia.
authors.forename: Shamus
authors.initials: S
authors.lastname: O'Meagher
authors.affiliation: 4Department of Ophthalmology,Australian School of Advanced Medicine,Sydney,Australia.
authors.forename: John
authors.initials: J
authors.lastname: Leaney
authors.affiliation: 4Department of Ophthalmology,Australian School of Advanced Medicine,Sydney,Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Graham
authors.affiliation: 1Department of Cardiology,Royal Prince Alfred Hospital,Sydney,Australia.
authors.forename: David S
authors.initials: DS
authors.lastname: Celermajer
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001916:Brachial Artery / Q000503:physiopathology; D016022:Case-Control Studies; D002452:Cell Count; D003490:Cyanosis / Q000209:etiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006330:Heart Defects, Congenital / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D012161:Retinal Artery / Q000503:physiopathology; D012169:Retinal Vein / Q000503:physiopathology; D012307:Risk Factors
chemical_list: D019332:Endothelin-1; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: retina