Endothelial function following the Fontan operation

Abstract

Outcomes for children with most forms of congenital heart disease continue to improve. Nonetheless, long-term morbidity—such as progressive ventricular dysfunction and congestive heart failure—for patients with single ventricular lesions remains high. 1 Gentles T.L. Gauvreau K. Mayer Jr, J.E. Fishberger S.B. Burnett J. Colan S.D. Newburger J.W. Wernovsky G. Fontan operation in five hundred consecutive patients factors influencing early and late outcome. J Thorac Cardiovasc Surg. 1997; 114: 376-391 Abstract Full Text Full Text PDF PubMed Scopus (496) Google Scholar The factors that contribute to hemodynamic compromise are incompletely understood. Although abnormal mechanics of the single ventricle have been well documented, recent evidence suggests that there may be a complex interplay between the heart and the peripheral and pulmonary vasculature in patients after the Fontan operation. 2 Yang S.G. Rychik J. Mesenteric blood flow patterns a link to protein-losing enteropathy after the Fontan operation. Am J Cardiol. 2002; 90: 672-674 Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar , 3 Hiramatsu T. Imai Y. Takanashi Y. Seo K. Terada M. Aoki M. Nakazawa M. Time course of endothelin-1 and adrenomedullin after the Fontan procedure. Ann Thorac Surg. 1999; 68: 169-172 Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar In adults with congestive heart failure, endothelial dysfunction is common. 4 Katz S.D. Biasucci L. Sabba C. Strom J.A. Jondeau G. Galvao M. Solomon S. Nikolic S.D. Forman R. LeJemtel T.H. Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure. J Am Coll Cardiol. 1992; 19: 918-925 Abstract Full Text PDF PubMed Scopus (372) Google Scholar Perturbations of the nitric oxide pathway are believed to play a critical role in endothelial dysfunction in these patients, and therapies directed at enhancing nitric oxide production have been proposed. 5 Kubo S.H. Rector T.S. Bank A.J. Williams R.E. Heifetz S.M. Endothelium-dependent vasodilation is attenuated in patients with heart failure. Circulation. 1991; 84: 1589-1596 Crossref PubMed Scopus (700) Google Scholar , 6 Drexler H. Kästner S. Strobel A. Studer R. Brodde O.E. Hasenfuss G. Expression, activity and functional significance of inducible nitric oxide synthase in the failing human heart. J Am Coll Cardiol. 1998; 32: 955-963 Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar Several previous studies have suggested that the nitric oxide pathway is also abnormal in patients after the Fontan procedure. 3 Hiramatsu T. Imai Y. Takanashi Y. Seo K. Terada M. Aoki M. Nakazawa M. Time course of endothelin-1 and adrenomedullin after the Fontan procedure. Ann Thorac Surg. 1999; 68: 169-172 Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar , 7 Gorenflo M. Zheng C. Werle E. Fiehn W. Ulmer H.E. Plasma levels of asymmetrical dimethyl-L-arginine in patients with congenital heart disease and pulmonary hypertension. J Cardiovasc Pharmacol. 2001; 37: 489-492 Crossref PubMed Scopus (134) Google Scholar These findings have particular importance because improving the endothelial response in Fontan patients has the potential to reduce of the risk of developing congestive heart failure. In the present study, we studied the endothelial function in a group of asymptomatic patients who underwent the Fontan operation. In addition, we examined factors that influence endothelial function, including abnormalities of the nitric oxide pathway.