Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-15T09:20:17.216Z Has data issue: false hasContentIssue false
  • English
  • Français

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: david.celermajer@email.cs.nsw.gov.au
Get access Rights & Permissions [Opens in a new window]

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 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Engelfriet, P, Boersma, E, Oechslin, E, et al. The spectrum of adult congenital heart disease in Europe: morbidity and mortality in a 5 year follow-up period. The Euro Heart Survey on adult congenital heart disease. Eur Heart J 2005; 26: 2325–2333.CrossRefGoogle Scholar
2. Deanfield, JE, Halcox, JP, Rabelink, TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation 2007; 115: 1285–1295.Google Scholar
3. Katz, SD, Hryniewicz, K, Hriljac, I, et al. Vascular endothelial dysfunction and mortality risk in patients with chronic heart failure. Circulation 2005; 111: 310–314.Google Scholar
4. Schmidt-Lucke, C, Rossig, L, Fichtlscherer, S, et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 2005; 111: 2981–2987.CrossRefGoogle ScholarPubMed
5. Hill, JM, Zalos, G, Halcox, JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003; 348: 593–600.Google Scholar
6. Diller, GP, van Eijl, S, Okonko, DO, et al. Circulating endothelial progenitor cells in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension. Circulation 2008; 117: 3020–3030.CrossRefGoogle ScholarPubMed
7. Polak, K, Dorner, G, Kiss, B, et al. Evaluation of the Zeiss retinal vessel analyser. Br J Ophthalmol 2000; 84: 1285–1290.Google Scholar
8. Dorner, GT, Garhofer, G, Kiss, B, et al. Nitric oxide regulates retinal vascular tone in humans. Am J Physiol Heart Circ Physiol 2003; 285: H631–H636.Google Scholar
9. Celermajer, DS. Reliable endothelial function testing: at our fingertips? Circulation 2008; 117: 2428–2430.Google Scholar
10. Vallance, P, Leone, A, Calver, A, Collier, J, Moncada, S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992; 339: 572–575.Google Scholar
11. Hasdai, D, Holmes, DR Jr., Garratt, KN, Edwards, WD, Lerman, A. Mechanical pressure and stretch release endothelin-1 from human atherosclerotic coronary arteries in vivo. Circulation 1997; 95: 357–362.CrossRefGoogle ScholarPubMed
12. Halliwell, B, Zhao, K, Whiteman, M. Nitric oxide and peroxynitrite. The ugly, the uglier and the not so good: a personal view of recent controversies. Free Radic Res 1999; 31: 651–669.Google Scholar
13. Anand, IS, Latini, R, Florea, VG, et al. C-reactive protein in heart failure: prognostic value and the effect of valsartan. Circulation 2005; 112: 1428–1434.Google Scholar
14. Lin, Y, Weisdorf, DJ, Solovey, A, Hebbel, RP. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 2000; 105: 71–77.Google Scholar
15. Hochberg, Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika 1988; 75: 800–802.CrossRefGoogle Scholar
16. Ammash, N, Warnes, CA. Cerebrovascular events in adult patients with cyanotic congenital heart disease. J Am Coll Cardiol 1996; 28: 768–772.Google Scholar
17. Perloff, JK, Hart, EM, Greaves, SM, Miner, PD, Child, JS. Proximal pulmonary arterial and intrapulmonary radiologic features of Eisenmenger syndrome and primary pulmonary hypertension. Am J Cardiol 2003; 92: 182–187.CrossRefGoogle ScholarPubMed
18. Lerman, A, Zeiher, AM. Endothelial function: cardiac events. Circulation 2005; 111: 363–368.Google Scholar
19. Fischer, D, Rossa, S, Landmesser, U, et al. Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death. Eur Heart J 2005; 26: 65–69.Google Scholar
20. Andrews, NP, Prasad, A, Quyyumi, AA. N-acetylcysteine improves coronary and peripheral vascular function. J Am Coll Cardiol 2001; 37: 117–123.Google Scholar
21. Rector, TS, Bank, AJ, Mullen, KA, et al. Randomized, double-blind, placebo-controlled study of supplemental oral l-arginine in patients with heart failure. Circulation 1996; 93: 2135–2141.Google Scholar
22. Oechslin, E, Kiowski, W, Schindler, R, Bernheim, A, Julius, B, Brunner-La Rocca, HP. Systemic endothelial dysfunction in adults with cyanotic congenital heart disease. Circulation 2005; 112: 1106–1112.CrossRefGoogle ScholarPubMed
23. Pedersen, CM, Schmidt, MR, Mortensen, B, et al. Preserved flow-mediated dilation in adults with cyanotic congenital heart disease. Pediatr Cardiol 2009; 30: 965–970.CrossRefGoogle ScholarPubMed
24. Nguyen, TT, Kawasaki, R, Wang, JJ, et al. Flicker light-induced retinal vasodilation in diabetes and diabetic retinopathy. Diabetes Care 2009; 32: 2075–2080.CrossRefGoogle ScholarPubMed
25. Schiel, R, Vilser, W, Kovar, F, Kramer, G, Braun, A, Stein, G. Retinal vessel response to flicker light in children and adolescents with type 1 diabetes mellitus and overweight or obesity. Diabetes Res Clin Pract 2009; 83: 358–364.Google Scholar
26. Fadini, GP, Baesso, I, Albiero, M, Sartore, S, Agostini, C, Avogaro, A. Technical notes on endothelial progenitor cells: ways to escape from the knowledge plateau. Atherosclerosis 2008; 197: 496–503.CrossRefGoogle ScholarPubMed
27. Han, TH, Perloff, JK, Liao, JC. Nitric oxide metabolism in adults with cyanotic congenital heart disease. Am J Cardiol 2007; 99: 691–695.CrossRefGoogle ScholarPubMed
28. Wolff, B, Lodziewski, S, Bollmann, T, Opitz, CF, Ewert, R. Impaired peripheral endothelial function in severe idiopathic pulmonary hypertension correlates with the pulmonary vascular response to inhaled iloprost. Am Heart J 2007; 153: e1–e7.Google Scholar
29. Armstead, WM. Opioids and nitric oxide contribute to hypoxia-induced pial arterial vasodilation in newborn pigs. Am J Physiol 1995; 268: H226–H232.Google Scholar
30. Pape, D, Beuchard, J, Guillo, P, Allain, H, Bellissant, E. Hypoxic contractile response in isolated rat thoracic aorta: role of endothelium, extracellular calcium and endothelin. Fundam Clin Pharmacol 1997; 11: 121–126.Google Scholar
31. Toporsian, M, Govindaraju, K, Nagi, M, Eidelman, D, Thibault, G, Ward, ME. Downregulation of endothelial nitric oxide synthase in rat aorta after prolonged hypoxia in vivo. Circ Res 2000; 86: 671–675.Google Scholar
32. Tsai, AG, Friesenecker, B, McCarthy, M, Sakai, H, Intaglietta, M. Plasma viscosity regulates capillary perfusion during extreme hemodilution in hamster skinfold model. Am J Physiol 1998; 275: H2170–H2180.Google Scholar
33. Pries, AR, Neuhaus, D, Gaehtgens, P. Blood viscosity in tube flow: dependence on diameter and hematocrit. Am J Physiol 1992; 263: H1770–H1778.Google Scholar
34. Ogunshola, OO, Djonov, V, Staudt, R, Vogel, J, Gassmann, M. Chronic excessive erythrocytosis induces endothelial activation and damage in mouse brain. Am J Physiol Regul Integr Comp Physiol 2006; 290: R678–R684.CrossRefGoogle ScholarPubMed
35. Belhassen, L, Pelle, G, Sediame, S, et al. Endothelial dysfunction in patients with sickle cell disease is related to selective impairment of shear stress-mediated vasodilation. Blood 2001; 97: 1584–1589.Google Scholar
Supplementary material: File

Cordina Supplementary Material

Supplementary Material

Download Cordina Supplementary Material(File)
File 513.1 KB