Abstract
IntroductionTransposition of the great arteries (TGA) is a cyanotic congenital heart defect that requires surgical correction, with the use of cardiopulmonary-bypass (CPB), usually within 3 weeks of life. The use of CPB in open heart surgery results in brain hypoperfusion and in a powerful systemic inflammatory response and oxidative stress.ObjectiveWe aimed to develop a novel untargeted metabolomics approach to detect early postoperative changes in metabolic profile following neonatal cardiac surgery.MethodsWe studied 14 TGA newborns with intact ventricular septum undergoing arterial switch operation with the use of CPB. Urine samples were collected preoperatively and at the end of the surgery and were analyzed using an untargeted metabolomics approach based on UHPLC-high resolution mass spectrometry.ResultsSince post surgery metabolic spectra were heavily contaminated by metabolites derived from administered drugs, we constructed a list of drugs used during surgery and their related metabolites retrieved from urine samples. This library was applied to our samples and 1255 drugs and drug metabolites were excluded from the analysis. Afterward, we detected over 39,000 unique compounds and 371 putatively annotated metabolites were different between pre and post-surgery samples. Among these metabolites, 13 were correctly annotated or identified. Metabolites linked to kynurenine pathway of tryptophan degradation displayed the highest fold change.ConclusionsThis is the first report on metabolic response to cardiac surgery in TGA newborns. We developed an experimental design that allowed the identification of perturbed metabolic pathways and potential biomarkers of brain damage, limiting drugs interference in the analysis.
Highlights
Transposition of the great arteries (TGA) is a cyanotic congenital heart defect that requires surgical correction, with the use of cardiopulmonary-bypass (CPB), usually within 3 weeks of life
Because the dynamics of the human body are mirrored in the metabolome, we hypothesize that CPB-induced neuroinflammation/oxidative damage could be associated with an altered urine metabolite composition.To address this hypothesis, we performed high resolution mass spectrometry-based untargeted metabolomic of urine samples collected before and after CPB from newborns with TGA and we developed a novel data analysis workflow useful to clear the metabolites deriving from administered drugs out of the urinary metabolic profile
Fourteen newborns with TGA undergoing elective arterial switch operation (ASO) were included in this study
Summary
Transposition of the great arteries (TGA) is a cyanotic congenital heart defect that requires surgical correction, with the use of cardiopulmonary-bypass (CPB), usually within 3 weeks of life. Results Since post surgery metabolic spectra were heavily contaminated by metabolites derived from administered drugs, we constructed a list of drugs used during surgery and their related metabolites retrieved from urine samples. The first one sends deoxygenated systemic venous blood to the right atrium and back to the systemic circulation via the right ventricle and aorta; the second one sends oxygenated pulmonary venous blood to the left atrium and back to the lungs via the left ventricle and pulmonary artery This will lead to profound hypoxic state pre- and postnatally until cardiac surgery is accomplished. Neonatal arterial switch operation (ASO) is the treatment of choice for infants with D-TGA and it is usually performed within 3 weeks of life (Authors/Task Force et al 2017)
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