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Urinary metabolomics reveals kynurenine pathway perturbation in newborns with transposition of great arteries after surgical repair.

ABSTRACT: INTRODUCTION: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. The use of CPB in open heart surgery results in brain hypoperfusion and in a powerful systemic inflammatory response and oxidative stress. OBJECTIVE:We aimed to develop a novel untargeted metabolomics approach to detect early postoperative changes in metabolic profile following neonatal cardiac surgery. METHODS:We 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. 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. 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. CONCLUSIONS:This 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.

SUBMITTER: Simonato M

PROVIDER: S-EPMC6817811 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Urinary metabolomics reveals kynurenine pathway perturbation in newborns with transposition of great arteries after surgical repair.

Simonato Manuela M Fochi Igor I Vedovelli Luca L Giambelluca Sonia S Carollo Cristiana C Padalino Massimo M Carnielli Virgilio P VP Cogo Paola P

Metabolomics : Official journal of the Metabolomic Society 20191028 11

<h4>Introduction</h4>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. The use of CPB in open heart surgery results in brain hypoperfusion and in a powerful systemic inflammatory response and oxidative stress.<h4>Objective</h4>We aimed to develop a novel untargeted metabolomics approach to detect early postoperative changes in metabolic profile following ...[more]

PMID: 31659512

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Project description:ObjectivesTo use 4D-flow MRI to describe systemic and non-systemic ventricular flow organisation and energy loss in patients with repaired d-transposition of the great arteries (d-TGA) and normal subjects.MethodsPathline tracking of ventricular volumes was performed using 4D-flow MRI data from a 1.5-T GE Discovery MR450 scanner. D-TGA patients following arterial switch (n = 17, mean age 14 ± 5 years) and atrial switch (n = 15, 35 ± 6 years) procedures were examined and compared with subjects with normal cardiac anatomy and ventricular function (n = 12, 12 ± 3 years). Pathlines were classified by their passage through the ventricles as direct flow, retained inflow, delayed ejection flow, and residual volume and visually and quantitatively assessed. Additionally, viscous energy losses (ELv) were calculated.ResultsIn normal subjects, the ventricular flow paths were well ordered following similar trajectories through the ventricles with very little mixing of flow components. The flow paths in all atrial and some arterial switch patients were more irregular with high mixing. Direct flow and delayed ejection flow were decreased in atrial switch patients' systemic ventricles with a corresponding increase in residual volume compared with normal subjects (p = 0.003 and p < 0.001 respectively) and arterial switch patients (p < 0.0001 and p < 0.001 respectively). In non-systemic ventricles, arterial switch patients had increased direct flow and decreased delayed ejection fractions compared to normal (p = 0.007 and p < 0.001 respectively) and atrial switch patients (p = 0.01 and p < 0.001 respectively). Regions of high levels of mixing of ventricular flow components showed elevated ELv.Conclusions4D-flow MRI pathline tracking reveals disordered ventricular flow patterns and associated ELv in d-TGA patients.Key points• 4D-flow MRI can be used to assess intraventricular flow dynamics in d-TGA patients. • d-TGA arterial switch patients mostly show intraventricular flow dynamics representative of normal subjects, while atrial switch patients show increased flow disorder and different proportions of intraventricular flow volumes. • Flow disruption and disorder increase viscous energy losses.

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Urinary metabolomics reveals kynurenine pathway perturbation in newborns with transposition of great arteries after surgical repair.

Publications

Urinary metabolomics reveals kynurenine pathway perturbation in newborns with transposition of great arteries after surgical repair.

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