Arginine-NO metabolites are associated with morbidity in single ventricle infants undergoing stage 2 palliation.

Autor: Frank BS; University of Colorado Department of Pediatrics, Section of Cardiology, Denver, CO, USA. Benjamin.Frank@childrenscolorado.org., Niemiec S; University of Colorado Department of Biostatistics and Informatics, Denver, CO, USA., Khailova L; University of Colorado Department of Pediatrics, Section of Cardiology, Denver, CO, USA., Mancuso CA; University of Colorado Department of Biostatistics and Informatics, Denver, CO, USA., Lehmann T; University of Colorado Department of Pediatrics, Section of Cardiology, Denver, CO, USA., Mitchell MB; University of Colorado Department of Surgery, Denver, CO, USA., Morgan GJ; University of Colorado Department of Pediatrics, Section of Cardiology, Denver, CO, USA., Twite M; University of Colorado Department of Anesthesiology, Denver, CO, USA., DiMaria MV; University of Colorado Department of Pediatrics, Section of Cardiology, Denver, CO, USA., Klawitter J; University of Colorado Department of Anesthesiology, Denver, CO, USA., Davidson JA; University of Colorado Department of Pediatrics, Section of Cardiology, Denver, CO, USA.
Jazyk: angličtina
Zdroj: Pediatric research [Pediatr Res] 2024 Jul; Vol. 96 (2), pp. 347-355. Date of Electronic Publication: 2024 Apr 02.
DOI: 10.1038/s41390-024-03162-y
Abstrakt: Background: Infants 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.
Methods: Prospective 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.
Results: Pre-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).
Conclusion: Arginine 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.
(© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)
Databáze: MEDLINE
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