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Widespread endotheliopathy in adults with cyanotic congenital heart disease

Published online by Cambridge University Press:  25 March 2014

Rachael L. Cordina ,
Shirley Nakhla ,
Shamus O’Meagher ,
John Leaney ,
Stuart Graham  and
David S. Celermajer
Rachael L. Cordina
Affiliation:
Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia Department of Cardiology, Sydney Medical School, Sydney, Australia Heart Research Institute, Sydney, Australia
Shirley Nakhla
Affiliation:
Heart Research Institute, Sydney, Australia
Shamus O’Meagher
Affiliation:
Department of Cardiology, Sydney Medical School, Sydney, Australia
John Leaney
Affiliation:
Department of Ophthalmology, Australian School of Advanced Medicine, Sydney, Australia
Stuart Graham
Affiliation:
Department of Ophthalmology, Australian School of Advanced Medicine, Sydney, Australia
David S. Celermajer*
Affiliation:
Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia Department of Cardiology, Sydney Medical School, Sydney, Australia Heart Research Institute, Sydney, Australia
*
Correspondence: D. S. Celermajer, Department of Cardiology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW 2050, Australia. Tel: +612 9515 6111; Fax: +612 9550 6262; E-mail: [email protected]
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Abstract

Introduction: 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.

Keywords

Cyanosisendotheliumendothelial dysfunctioncongenital heart diseaseretina
Type
Original Articles
Information
Cardiology in the Young , Volume 25 , Issue 3 , March 2015 , pp. 511 - 519
Copyright
© Cambridge University Press 2014 

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