Eur J Cardiothorac Surg. 2025 Sep 23:ezaf311. doi: 10.1093/ejcts/ezaf311. Online ahead of print.
ABSTRACT
OBJECTIVES: 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).
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
PMID:40985729 | DOI:10.1093/ejcts/ezaf311
