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Normoxic Management during Cardiopulmonary Bypass Does Not Reduce Cerebral Mitochondrial Dysfunction in Neonatal Swine.

Authors :
Aronowitz DI
Geoffrion TR
Piel S
Morton SR
Starr J
Melchior RW
Gaudio HA
Degani R
Widmann NJ
Weeks MK
Ranieri NR
Benson E
Ko TS
Licht DJ
Hefti M
Gaynor JW
Kilbaugh TJ
Mavroudis CD
Source :
International journal of molecular sciences [Int J Mol Sci] 2024 May 17; Vol. 25 (10). Date of Electronic Publication: 2024 May 17.
Publication Year :
2024

Abstract

Optimal oxygen management during pediatric cardiopulmonary bypass (CPB) is unknown. We previously demonstrated an increase in cortical mitochondrial reactive oxygen species and decreased mitochondrial function after CPB using hyperoxic oxygen management. This study investigates whether controlled oxygenation (normoxia) during CPB reduces cortical mitochondrial dysfunction and oxidative injury. Ten neonatal swine underwent three hours of continuous CPB at 34 °C (flow > 100 mL/kg/min) via cervical cannulation targeting a partial pressure of arterial oxygen (PaO <subscript>2</subscript> ) goal < 150 mmHg (normoxia, n = 5) or >300 mmHg (hyperoxia, n = 5). The animals underwent continuous hemodynamic monitoring and serial arterial blood sampling. Cortical microdialysate was serially sampled to quantify the glycerol concentration (represents neuronal injury) and lactate-to-pyruvate ratio (represents bioenergetic dysfunction). The cortical tissue was analyzed via high-resolution respirometry to quantify mitochondrial oxygen consumption and reactive oxygen species generation, and cortical oxidized protein carbonyl concentrations were quantified to assess for oxidative damage. Serum PaO <subscript>2</subscript> was higher in hyperoxia animals throughout CPB ( p < 0.001). There were no differences in cortical glycerol concentration between groups ( p > 0.2). The cortical lactate-to-pyruvate ratio was modestly elevated in hyperoxia animals ( p < 0.03) but the values were not clinically significant (<30). There were no differences in cortical mitochondrial respiration ( p = 0.48), protein carbonyls ( p = 0.74), or reactive oxygen species generation ( p = 0.93) between groups. Controlled oxygenation during CPB does not significantly affect cortical mitochondrial function or oxidative injury in the acute setting. Further evaluation of the short and long-term effects of oxygen level titration during pediatric CPB on cortical tissue and other at-risk brain regions are needed, especially in the presence of cyanosis.

Details

Language :
English
ISSN :
1422-0067
Volume :
25
Issue :
10
Database :
MEDLINE
Journal :
International journal of molecular sciences
Publication Type :
Academic Journal
Accession number :
38791504
Full Text :
https://doi.org/10.3390/ijms25105466