Increased cerebral mitochondrial dysfunction and reactive oxygen species with cardiopulmonary bypass

Lindsay E Volk; Constantine D Mavroudis; Tiffany Ko; Thomas Hallowell; Nile Delso; Anna L Roberts; Jonathan Starr; William Landis; Yuxi Lin; Marco Hefti; Ryan W Morgan; Richard W Melchior; Tami M Rosenthal; Alexander Chappell; Douglas Fisher; Molly Dreher; Daniel J Licht; Jonathan Chen; J. William Gaynor; Christopher E Mascio; Todd J Kilbaugh

doi:10.1093/ejcts/ezaa439

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Increased cerebral mitochondrial dysfunction and reactive oxygen species with cardiopulmonary bypass

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Increased cerebral mitochondrial dysfunction and reactive oxygen species with cardiopulmonary bypass

Lindsay E Volk, Constantine D Mavroudis, Tiffany Ko, Thomas Hallowell, Nile Delso, Anna L Roberts, Jonathan Starr, William Landis, Yuxi Lin, Marco Hefti, …

European journal of cardio-thoracic surgery, Vol.59(6), pp.1256-1264

06/14/2021

DOI: 10.1093/ejcts/ezaa439

PMCID: PMC8203249

PMID: 33367535

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Abstract

Abstract OBJECTIVES Neurodevelopmental injury after cardiac surgery using cardiopulmonary bypass (CPB) for congenital heart defects is common, but the mechanism behind this injury is unclear. This study examines the impact of CPB on cerebral mitochondrial reactive oxygen species (ROS) generation and mitochondrial bioenergetics. METHODS Twenty-three piglets (mean weight 4.2 ± 0.5 kg) were placed on CPB for either 1, 2, 3 or 4 h (n = 5 per group) or underwent anaesthesia without CPB (sham, n = 3). Microdialysis was used to measure metabolic markers of ischaemia. At the conclusion of CPB or 4 h of sham, brain tissue was harvested. Utilizing high-resolution respirometry, with simultaneous fluorometric analysis, mitochondrial respiration and ROS were measured. RESULTS There were no significant differences in markers of ischaemia between sham and experimental groups. Sham animals had significantly higher mitochondrial respiration than experimental animals, including maximal oxidative phosphorylation capacity of complex I (OXPHOSCI) (3.25 ± 0.18 vs 4-h CPB: 1.68 ± 0.10, P < 0.001) and maximal phosphorylating respiration capacity via convergent input through complexes I and II (OXPHOSCI+CII) (7.40 ± 0.24 vs 4-h CPB: 3.91 ± 0.20, P < 0.0001). At 4-h, experimental animals had significantly higher ROS related to non-phosphorylating respiration through complexes I and II (ETSCI+CII) than shams (1.08 ± 0.13 vs 0.64 ± 0.04, P = 0.026). CONCLUSIONS Even in the absence of local markers of ischaemia, CPB is associated with decreased mitochondrial respiration relative to shams irrespective of duration. Exposure to 4 h of CPB resulted in a significant increase in cerebral mitochondrial ROS formation compared to shorter durations. Further study is needed to improve the understanding of cerebral mitochondrial health and its effects on the pathophysiology of neurological injury following exposure to CPB.

Details

Title: Subtitle: Increased cerebral mitochondrial dysfunction and reactive oxygen species with cardiopulmonary bypass
Creators: Lindsay E Volk - Division of Cardiothoracic Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Constantine D Mavroudis - Division of Cardiothoracic Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Tiffany Ko - Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Thomas Hallowell
Nile Delso - Division of Anesthesia and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Anna L Roberts - Division of Anesthesia and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Jonathan Starr - Division of Anesthesia and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
William Landis - Division of Anesthesia and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Yuxi Lin - Division of Anesthesia and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Marco Hefti - University of Iowa, Pathology
Ryan W Morgan - Division of Anesthesia and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Richard W Melchior - Division of Perfusion Services, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Tami M Rosenthal - Division of Perfusion Services, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Alexander Chappell - Children's Hospital of Philadelphia
Douglas Fisher - Children's Hospital of Philadelphia
Molly Dreher - Children's Hospital of Philadelphia
Daniel J Licht - Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Jonathan Chen - Children's Hospital of Philadelphia
J. William Gaynor - Division of Cardiothoracic Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Christopher E Mascio - Division of Cardiothoracic Surgery, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Todd J Kilbaugh - Division of Anesthesia and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Resource Type: Journal article
Publication Details: European journal of cardio-thoracic surgery, Vol.59(6), pp.1256-1264
DOI: 10.1093/ejcts/ezaa439
PMID: 33367535
PMCID: PMC8203249
NLM abbreviation: Eur J Cardiothorac Surg
ISSN: 1010-7940
eISSN: 1873-734X
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: T32-HL007915, P41-EB015893; name: Children’s Hospital of Philadelphia, Department of Anesthesiology and Critical Care and funds from the Alice Langdon Warner and Daniel S; name: Tabas Endowed Chairs in Paediatric Cardiac Surgery at the Children’s Hospital of Philadelphia
Language: English
Date published: 06/14/2021
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984186497202771

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