Elevated serum neurologic biomarker profiles after cardiac arrest in a porcine model

Kumaran Senthil; Abhay Ranganathan; Sarah Piel; Marco M. Hefti; Ron W. Reeder; Matthew P. Kirschen; Jonathan Starr; Sarah Morton; Hunter A. Gaudio; Julia C. Slovis; Jeremy R. Herrmann; Robert A. Berg; Todd J. Kilbaugh; Ryan W. Morgan

doi:10.1016/j.resplu.2024.100726

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Elevated serum neurologic biomarker profiles after cardiac arrest in a porcine model

Journal article

Open access

Peer reviewed

Elevated serum neurologic biomarker profiles after cardiac arrest in a porcine model

Kumaran Senthil, Abhay Ranganathan, Sarah Piel, Marco M. Hefti, Ron W. Reeder, Matthew P. Kirschen, Jonathan Starr, Sarah Morton, Hunter A. Gaudio, Julia C. Slovis, …

Resuscitation plus, Vol.19, 100726

09/2024

DOI: 10.1016/j.resplu.2024.100726

PMCID: PMC11325790

PMID: 39149222

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Abstract

Swine exhibit cerebral cortex mitochondrial dysfunction and neuropathologic injury after hypoxic cardiac arrest treated with hemodynamic-directed CPR (HD-CPR) despite normal Cerebral Performance Category scores. We analyzed the temporal evolution of plasma protein biomarkers of brain injury and inflammatory cytokines, as well as cerebral cortical mitochondrial injury and neuropathology for five days following pediatric asphyxia-associated cardiac arrest treated with HD-CPR. One-month-old swine underwent asphyxia associated cardiac arrest, 10–20 min of HD-CPR (goal SBP 90 mmHg, coronary perfusion pressure 20 mmHg), and randomization to post-ROSC survival duration (24, 48, 72, 96, 120 h; n = 3 per group) with standardized post-resuscitation care. Plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and cytokine levels were collected pre-injury and 1, 6, 24, 48, 72, 96, and 120 h post-ROSC. Cerebral cortical tissue was assessed for: mitochondrial respirometry, mass, and dynamic proteins; oxidative injury; and neuropathology. Relative to pre-arrest baseline (9.4 pg/ml [6.7–12.6]), plasma NfL was increased at all post-ROSC time points. Each sequential NfL measurement through 48 h was greater than the previous value {1 h (12.7 pg/ml [8.4–14.6], p = 0.01), 6 h (30.9 pg/ml [17.7–44.0], p = 0.0004), 24 h (59.4 pg/ml [50.8–96.1], p = 0.0003) and 48 h (85.7 pg/ml [61.9–118.7], p = 0.046)}. Plasma GFAP, inflammatory cytokines or cerebral cortical tissue measurements were not demonstrably different between time points. In a swine model of pediatric cardiac arrest, plasma NfL had an upward trajectory until 48 h post-ROSC after which it remained elevated through five days, suggesting it may be a sensitive marker of neurologic injury following pediatric cardiac arrest.

Biomarkers

Pediatrics

Cardiac arrest

Neurologic injury

Details

Title: Subtitle: Elevated serum neurologic biomarker profiles after cardiac arrest in a porcine model
Creators: Kumaran Senthil - University of Pennsylvania
Abhay Ranganathan - Children's Hospital of Philadelphia
Sarah Piel - Children's Hospital of Philadelphia
Marco M. Hefti - University of Iowa
Ron W. Reeder - University of Utah
Matthew P. Kirschen - University of Pennsylvania
Jonathan Starr - Children's Hospital of Philadelphia
Sarah Morton - Children's Hospital of Philadelphia
Hunter A. Gaudio - Children's Hospital of Philadelphia
Julia C. Slovis - University of Pennsylvania
Jeremy R. Herrmann - University of Pennsylvania
Robert A. Berg - University of Pennsylvania
Todd J. Kilbaugh - University of Pennsylvania
Ryan W. Morgan - University of Pennsylvania
Resource Type: Journal article
Publication Details: Resuscitation plus, Vol.19, 100726
DOI: 10.1016/j.resplu.2024.100726
PMID: 39149222
PMCID: PMC11325790
NLM abbreviation: Resusc Plus
ISSN: 2666-5204
eISSN: 2666-5204
Publisher: Elsevier B.V
Language: English
Date published: 09/2024
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984687787302771

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