Journal article
Normoxic Management during Cardiopulmonary Bypass Does Not Reduce Cerebral Mitochondrial Dysfunction in Neonatal Swine
International journal of molecular sciences, Vol.25(10), 5466
05/15/2024
DOI: 10.3390/ijms25105466
PMCID: PMC11122014
PMID: 38791504
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 (PaO2) 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 PaO2 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
- Title: Subtitle
- Normoxic Management during Cardiopulmonary Bypass Does Not Reduce Cerebral Mitochondrial Dysfunction in Neonatal Swine
- Creators
- Danielle Aronowitz - Children's Hospital of PhiladelphiaTracy Geoffrion - Children's Hospital of PhiladelphiaSarah Piel - Children's Hospital of PhiladelphiaSarah Morton - Children's Hospital of PhiladelphiaJonathan Starr - Children's Hospital of PhiladelphiaRichard Melchior - Children's Hospital of PhiladelphiaHunter Gaudio - Children's Hospital of PhiladelphiaRinat Degani - Children's Hospital of PhiladelphiaNicholas Widmann - Children's Hospital of PhiladelphiaM WeeksNicolina Ranieri - Children's Hospital of PhiladelphiaEmilie Benson - Children's Hospital of PhiladelphiaTiffany Ko - University of PennsylvaniaDaniel Licht - Children's Hospital of PhiladelphiaMarco Hefti - University of IowaJ GaynorTodd Kilbaugh - Children's Hospital of PhiladelphiaConstantine Mavroudis - Children's Hospital of Philadelphia
- Resource Type
- Journal article
- Publication Details
- International journal of molecular sciences, Vol.25(10), 5466
- Publisher
- MDPI AG
- DOI
- 10.3390/ijms25105466
- PMID
- 38791504
- PMCID
- PMC11122014
- ISSN
- 1661-6596
- eISSN
- 1422-0067
- Language
- English
- Date published
- 05/15/2024
- Academic Unit
- Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984628217902771
Metrics
7 Record Views