Haemodynamic-directed cardiopulmonary resuscitation promotes mitochondrial fusion and preservation of mitochondrial mass after successful resuscitation in a pediatric porcine model

Kumaran Senthil; Ryan W Morgan; Marco M Hefti; Michael Karlsson; Andrew J Lautz; Constantine D Mavroudis; Tiffany Ko; Vinay M Nadkarni; Johannes Ehinger; Robert A Berg; Robert M Sutton; Francis X McGowan; Todd J Kilbaugh

doi:10.1016/j.resplu.2021.100124

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Haemodynamic-directed cardiopulmonary resuscitation promotes mitochondrial fusion and preservation of mitochondrial mass after successful resuscitation in a pediatric porcine model

Journal article

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Haemodynamic-directed cardiopulmonary resuscitation promotes mitochondrial fusion and preservation of mitochondrial mass after successful resuscitation in a pediatric porcine model

Kumaran Senthil, Ryan W Morgan, Marco M Hefti, Michael Karlsson, Andrew J Lautz, Constantine D Mavroudis, Tiffany Ko, Vinay M Nadkarni, Johannes Ehinger, Robert A Berg, …

Resuscitation Plus, Vol.6, p.100124

06/2021

DOI: 10.1016/j.resplu.2021.100124

PMCID: PMC8244484

PMID: 34223382

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Abstract

Cerebral mitochondrial dysfunction is a key mediator of neurologic injury following cardiac arrest (CA) and is regulated by the balance of fusion and fission (mitochondrial dynamics). Under stress, fission can decrease mitochondrial mass and signal apoptosis, while fusion promotes oxidative phosphorylation efficiency. This study evaluates mitochondrial dynamics and content in brain tissue 24h after CA between two cardiopulmonary resuscitation (CPR) strategies. Piglets (1 month), previously randomized to three groups: (1) Std-CPR (n=5); (2) HD-CPR (n=5; goal systolic blood pressure 90mmHg, goal coronary perfusion pressure 20mmHg); (3) Shams (n=7). Std-CPR and HD-CPR groups underwent 7min of asphyxia, 10min of CPR, and standardized post-resuscitation care. Primary outcomes: (1) cerebral cortical mitochondrial protein expression for fusion (OPA1, OPA1 long to short chain ratio, MFN2) and fission (DRP1, FIS1), and (2) mitochondrial mass by citrate synthase activity. Secondary outcomes: (1) intra-arrest haemodynamics and (2) cerebral performance category (CPC) at 24h. HD-CPR subjects had higher total OPA1 expression compared to Std-CPR (1.52; IQR 1.02–1.69 vs 0.67; IQR 0.54−0.88, p=0.001) and higher OPA1 long to short chain ratio than both Std-CPR (0.63; IQR 0.46−0.92 vs 0.26; IQR 0.26−0.31, p=0.016) and shams. Citrate synthase activity was lower in Std-CPR than sham (11.0; IQR 10.15–12.29 vs 13.4; IQR 12.28–15.66, p=0.047), but preserved in HD-CPR. HD-CPR subjects had improved intra-arrest haemodynamics and CPC scores at 24h compared to Std-CPR. Following asphyxia-associated CA, HD-CPR exhibits increased pro-mitochondrial fusion protein expression, preservation of mitochondrial mass, improved haemodynamics and superior neurologic scoring compared to Std-CPR. IAC 16-001023.

Mitochondria

Dynamics

Cardiopulmonary resuscitation

Cardiac arrest

Fusion

Neurologic outcomes

Fission

Details

Title: Subtitle: Haemodynamic-directed cardiopulmonary resuscitation promotes mitochondrial fusion and preservation of mitochondrial mass after successful resuscitation in a pediatric porcine model
Creators: Kumaran Senthil - Children’s Hospital of Philadelphia and Perelman School of Medicine at University of Pennsylvania, Department of Anesthesiology and Critical Care Medicine, United States
Ryan W Morgan - Children’s Hospital of Philadelphia and Perelman School of Medicine at University of Pennsylvania, Department of Anesthesiology and Critical Care Medicine, United States
Marco M Hefti - University of Iowa, Division of Pathology, United States
Michael Karlsson - Department of Neurosurgery, Righospitalet, Copenhagen, Denmark
Andrew J Lautz - Cincinnati Children’s Hospital Medical Center, Division of Critical Care Medicine, United States
Constantine D Mavroudis - Department of Neurosurgery, Righospitalet, Copenhagen, Denmark
Tiffany Ko - Children’s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Division of Neurology, United States
Vinay M Nadkarni - Children’s Hospital of Philadelphia and Perelman School of Medicine at University of Pennsylvania, Department of Anesthesiology and Critical Care Medicine, United States
Johannes Ehinger - Lund University, Mitochondrial Medicine, Sweden
Robert A Berg - Children’s Hospital of Philadelphia and Perelman School of Medicine at University of Pennsylvania, Department of Anesthesiology and Critical Care Medicine, United States
Robert M Sutton - Children’s Hospital of Philadelphia and Perelman School of Medicine at University of Pennsylvania, Department of Anesthesiology and Critical Care Medicine, United States
Francis X McGowan - Children’s Hospital of Philadelphia and Perelman School of Medicine at University of Pennsylvania, Department of Anesthesiology and Critical Care Medicine, United States
Todd J Kilbaugh - Children’s Hospital of Philadelphia and Perelman School of Medicine at University of Pennsylvania, Department of Anesthesiology and Critical Care Medicine, United States
Resource Type: Journal article
Publication Details: Resuscitation Plus, Vol.6, p.100124
DOI: 10.1016/j.resplu.2021.100124
PMID: 34223382
PMCID: PMC8244484
NLM abbreviation: Resusc Plus
ISSN: 2666-5204
Publisher: Elsevier B.V
Grant note: DOI: 10.13039/100000050, name: National Heart Lung and Blood Institute
Language: English
Date published: 06/2021
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984071606002771

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