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Endothelial nitric oxide synthase gene polymorphism (Glu298Asp) and acute pulmonary hypertension post cardiopulmonary bypass in children with congenital cardiac diseases

Published online by Cambridge University Press:  10 December 2010

Tsvetomir Loukanov ,
Katharina Hoss ,
Pentcho Tonchev ,
Homa Klimpel ,
Raul Arnold ,
Christian Sebening ,
Matthias Karck  and
Matthias Gorenflo
Tsvetomir Loukanov*
Affiliation:
Department of Cardiac Surgery, Surgical Clinic, University of Heidelberg, Germany
Katharina Hoss
Affiliation:
Department of Paediatric Cardiology, University of Heidelberg, Germany
Pentcho Tonchev
Affiliation:
Department of General Surgery, University of Pleven, Bulgaria
Homa Klimpel
Affiliation:
Department of Paediatric Cardiology, University of Heidelberg, Germany
Raul Arnold
Affiliation:
Department of Paediatric Cardiology, University of Heidelberg, Germany
Christian Sebening
Affiliation:
Department of Cardiac Surgery, Surgical Clinic, University of Heidelberg, Germany
Matthias Karck
Affiliation:
Department of Cardiac Surgery, Surgical Clinic, University of Heidelberg, Germany
Matthias Gorenflo
Affiliation:
Department of Paediatric Cardiology, University of Heidelberg, Germany
*
Correspondence to: Dr T. Loukanov, Department of Cardiac Surgery, Surgical Clinic, University of Heidelberg, D-69120 Heidelberg, INF 110, Germany. Tel: 004962215636274; Fax: 00496221565919; E-mail: [email protected]
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Abstract

Background

Intra-cardiac repair of congenital cardiac diseases in children with left–right shunt is often associated with acute elevation of pulmonary artery pressure following cardiopulmonary bypass. We studied the correlation between the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene and pulmonary hypertension in children with congenital cardiac diseases.

Methods and results

A total of 80 children with congenital cardiac diseases at a median age of 3.8 years, ranged 0.1–36.2 years, and 136 controls were enrolled. Most patients presented with significant left-to-right shunt – pulmonary-to-systemic blood flow of 2.8, with a range from 0.6 to 7.5. In all, 40 out of 80 children showed pulmonary hypertension with mean pressure of 42, ranged 26–82, millimetres of mercury. Thirty-one out of 40 children underwent intra-cardiac repair and 15 out of 31 operated patients were found to have an acute elevation of pulmonary artery pressure after cardiopulmonary bypass. The Glu298Asp polymorphism was identified using polymerase chain reaction and restriction fragment length polymorphism. Both in patients and in controls, the genotype distribution corresponded to the Hardy–Weinberg equilibrium. The gene frequency for Glu298Glu, Glu298Asp and Asp298Asp was not different in the control group compared to the patients (Armitage trend test: p = 0.37). The endothelial nitric oxide synthase polymorphism was related to acute post-operative elevation of pulmonary artery pressure (genotypic frequency 53.3 versus 25%; Armitage trend test: p = 0.038). In addition, the allelic frequency of the Glu298Asp was related to post-operative pulmonary hypertension (Fischer’s exact test: p = 0.048). The positive predictive value was 71.43%.

Conclusion

Patients with left-to-right shunt are more likely to develop acute elevation of pulmonary artery pressure after cardiopulmonary bypass when presenting with the Glu298Asp polymorphism of the gene endothelial nitric oxide synthase. This could be used as a genetic marker for the predisposition for the development of pulmonary hypertension after intra-cardiac repair.

Keywords

Cardiac surgerypost-operative complicationsprognostic factors
Type
Original Articles
Information
Cardiology in the Young , Volume 21 , Issue 2 , April 2011 , pp. 161 - 169
Copyright
Copyright © Cambridge University Press 2010

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