ArticlePediatric research2024
Arginine-NO metabolites are associated with morbidity in single ventricle infants undergoing stage 2 palliation.
Article in Pediatric research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
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4 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.
- Metabolomic profiling of infants undergoing cardiopulmonary bypass and association with clinical outcomes: a systematic review.Frontiers in cardiovascular medicine · 2024Pooled it
- L-Citrulline: Novel Pharmacotherapy to Improve Outcomes in Infants and Children at Risk of Systemic or Pulmonary Vascular Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Altered Arginine Metabolism in Children Undergoing Fontan Palliation: A Prospective Cohort Study.Pulmonary circulation · 2025Article
- Circulating amino acid levels in infants undergoing congenital heart disease surgery: near global decrease following cardiopulmonary bypass and impact of perioperative feeding patterns.Metabolomics : Official journal of the Metabolomic Society · 2025Article
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11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundInfants with single ventricle heart disease (SVHD) suffer morbidity from insufficient pulmonary blood flow, which may be related to impaired arginine metabolism. No prior study has reported quantitative mapping of arginine metabolites to evaluate the relationship between circulating metabolite levels and outcomes.
methodsProspective cohort study of 75 SVHD cases peri-Stage 2 and 50 healthy controls. We targeted pre- and post-op absolute serum quantification of 9 key members of the arginine metabolism pathway by tandem mass spectrometry. Primary outcomes were length of stay (LOS) and post-Stage 2 hypoxemia.
resultsPre-op cases showed alteration in 6 metabolites including decreased arginine and increased asymmetric dimethyl arginine (ADMA) levels compared to controls. Post-op cases demonstrated decreased arginine and citrulline levels persisting through 48 h. Adjusting for clinical variables, lower pre-op and 2 h post-op concentrations of multiple metabolites, including arginine and citrulline, were associated with longer post-op LOS (p < 0.01). Increased ADMA at 24 h was associated with greater post-op hypoxemia burden (p < 0.05).
conclusionArginine metabolism is impaired in interstage SVHD infants and is further deranged following Stage 2 palliation. Patients with greater metabolite alterations experience greater post-op morbidity. Decreased arginine metabolism may be an important driver of pathology in SVHD. IMPACT: Interstage infants with SVHD have significantly altered arginine-nitric oxide metabolism compared to healthy children with deficiency of multiple pathway intermediates persisting through 48 h post-Stage 2 palliation. After controlling for clinical covariates and classic catheterization-derived predictors of Stage 2 readiness, both lower pre-operation and lower post-operation circulating metabolite levels were associated with longer post-Stage 2 LOS while increased post-Stage 2 ADMA concentration was associated with greater post-op hypoxemia. Arginine metabolism mapping offers potential for development using personalized medicine strategies as a biomarker of Stage 2 readiness and therapeutic target to improve pulmonary vascular health in infants with SVHD.
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