Journal article
Branched-chain amino acids accumulate and glutamate decreases in cerebral interstitial fluid following cardiopulmonary bypass in neonatal swine
European journal of cardio-thoracic surgery, Vol.67(10), ezaf311
10/02/2025
DOI: 10.1093/ejcts/ezaf311
PMID: 40985729
Abstract
Dysregulated metabolism of the branched-chain amino acids (BCAAs-leucine, isoleucine, valine) can cause irreversible neurologic injury in neonates. BCAA metabolism is tightly linked to glutamate synthesis. Glutamate excitotoxicity has been implicated as a mechanism of neuronal injury following deep hypothermic circulatory arrest. This investigation explores glutamate and BCAA homeostasis following continuous cardiopulmonary bypass (CPB).
Fifteen neonatal swine underwent 3 hrs of continuous CPB and five animals each were survived for 12 hrs, 18 hrs, or 24 hrs post-CPB (N = 15). Three additional piglets underwent similar sham procedures and identical monitoring for 3 hrs without CPB (N = 3). Liquid chromatography-mass spectrometry was used to quantify metabolites in plasma, extracellular cerebral interstitial fluid (CIF), and cortical brain tissue samples collected at similar timepoints of analysis. Between-group and multiple comparisons tests were performed to identify differences in metabolomic profiles post-CPB.
Glutamate concentrations in CIF were lower than baseline at 12-24 hrs post-CPB (P = 0.015), but tended to increase in cortical brain tissue compared to sham animals (P = 0.095). In contrast, BCAAs were significantly elevated in extracellular CIF following CPB, and increased relative to plasma concentrations at 24 hrs post-CPB (leucine: P = 0.079; isoleucine: P = 0.044; valine: P = 0.043). However, BCAAs in cortical brain tissue were unchanged or tended to decrease compared to sham animals at 12-24 hrs CPB (leucine: P = 0.607; isoleucine: P = 0.067; valine: P = 0.912).
Following continuous CPB, BCAAs increase and glutamate decreases in extracellular CIF. Further investigations are warranted to elucidate how CPB and various neuroprotection strategies affect regional and cell type-specific changes in cerebral metabolism during critical periods of neurodevelopment.
Details
- Title: Subtitle
- Branched-chain amino acids accumulate and glutamate decreases in cerebral interstitial fluid following cardiopulmonary bypass in neonatal swine
- Creators
- Benjamin Smood - University of PennsylvaniaDanielle I Aronowitz - Children's Hospital of PhiladelphiaMichael Noji - Cardiovascular Institute HospitalClarissa Shoffler - Cardiovascular Institute HospitalDina Abbasian - Cardiovascular Institute HospitalChristopher Petucci - Cardiovascular Institute HospitalKimberly L Fiock - University of IowaMarco Hefti - University of IowaRinat Degani - Children's Hospital of PhiladelphiaRichard W Melchior - Children's Hospital of PhiladelphiaMichael Catalano - University of PennsylvaniaZoltan Arany - University of PennsylvaniaMarc Yudkoff - Children's Hospital of PhiladelphiaJ William Gaynor - University of PennsylvaniaTodd Kilbaugh - Children's Hospital of PhiladelphiaConstantine D Mavroudis - University of Pennsylvania
- Resource Type
- Journal article
- Publication Details
- European journal of cardio-thoracic surgery, Vol.67(10), ezaf311
- DOI
- 10.1093/ejcts/ezaf311
- PMID
- 40985729
- NLM abbreviation
- Eur J Cardiothorac Surg
- ISSN
- 1873-734X
- eISSN
- 1873-734X
- Publisher
- Oxford University Press
- Grant note
- Thoracic Surgery Foundation Nina Starr Braunwald Research Fellowship AwardChildren's Hospital of PhiladelphiaUniversity of Pennsylvania Institute for Translational Medicine and TherapeuticsNIH: TL1TR001880, F31CA261041
This study was supported by the Thoracic Surgery Foundation Nina Starr Braunwald Research Fellowship Award, as well as the Daniel M. Tabas, Thomas L. Spray, and William J. Greeley Endowed Chairs at the Children's Hospital of Philadelphia. Additional support was provided by the University of Pennsylvania Institute for Translational Medicine and Therapeutics, and the NIH (TL1TR001880; F31CA261041). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
- Language
- English
- Electronic publication date
- 09/23/2025
- Date published
- 10/02/2025
- Academic Unit
- Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984966335802771
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