Journal article
Abstract 203: Exploratory Study Of The Time Course Of Post-arrest Neurologic Injury In A Porcine Model Of Pediatric Cardiac Arrest
Circulation (New York, N.Y.), Vol.146(S_1), p.A203
11/08/2022
DOI: 10.1161/circ.146.suppl_1.203
Abstract
Byline: Kumaran Senthil, Anesthesiology and Critical Care Medicine, Children's Hosp of Philadelphia, Philadelphia, PA; Abhay Ranganathan, Anesthesiology and Critical Care Medicine, Children's Hosp of Philadelphia, Philadelphia, PA; Sarah Piel, Anesthesiology and Critical Care Medicine, Children's Hosp of Philadelphia, Philadelphia, PA; Marco M Hefti, Pathology, Univ of Iowa, Iowa City, IA; Julia C Slovis, Anesthesiology and Critical Care Medicine, Children's Hosp of Philadelphia, Philadelphia, PA; Robert A Berg, CHILDRENS HOSPITAL OF PHILADELPHIA, Philadelphia, PA; Todd J Kilbaugh, Anesthesiology and Critical Care Medicine, Children's Hosp of Philadelphia, Philadelphia, PA; Ryan W Morgan, Anesthesiology and Critical Care Medicine, Children's Hosp of Philadelphia, Philadelphia, PA Introduction: In preclinical models, hemodynamic-directed CPR (HD-CPR) mitigates post-arrest neurofunctional impairment and cerebral mitochondrial dysfunction. We aimed to explore the temporal evolution of markers of neurologic injury over five days following cardiac arrest treated with HD-CPR. Methods: Pigs (1-month-old) underwent 7min asphyxia, induction of ventricular fibrillation, 10-20min of HD-CPR (goal SBP 90 mmHg, coronary perfusion pressure 20mmHg), randomization to post-ROSC survival duration (24, 48, 72, 96, 120h; n=3 per group) with standardized post-resuscitation care. Plasma neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) were collected at 0, 6, 24, 48, 72, 96, 120h and compared by mixed effects analysis. At terminal endpoints, cerebral cortical tissue was assessed for: mitochondrial electron transport system function; citrate synthase quantification (mitochondrial mass); immunoblot quantification of mitochondrial dynamic proteins (Opa-1, MFN-2, DRP-1, FIS-1); ELISA for 4-HNE and protein carbonyls (oxidative injury); and neuropathologic examination for IBA-1 (microglial activation) and GFAP (reactive astrocytes), all compared via ANOVA. Results: All animals had swine cerebral performance category score of 1 (grossly normal) by 24h after injury. Plasma NFL was significantly elevated at 24, 48, 72, 96 (p<0.001) and 120h (p=0.009) compared to baseline. No significant differences were identified between time points for GFAP, mitochondrial measures, or neuropathological outcomes. Discussion: Despite grossly normal neurofunctional status, plasma NFL was elevated from baseline at multiple timepoints. No significant temporal differences were identified in other markers of neurologic injury. NFL may be a sensitive marker of mild neurologic injury post-arrest.
Details
- Title: Subtitle
- Abstract 203: Exploratory Study Of The Time Course Of Post-arrest Neurologic Injury In A Porcine Model Of Pediatric Cardiac Arrest
- Creators
- Kumaran SenthilAbhay RanganathanSarah PielMarco M HeftiJulia C SlovisRobert A BergTodd J Kilbaugh
- Resource Type
- Journal article
- Publication Details
- Circulation (New York, N.Y.), Vol.146(S_1), p.A203
- Publisher
- Lippincott Williams & Wilkins, WK Health
- DOI
- 10.1161/circ.146.suppl_1.203
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/08/2022
- Description audience
- Professional
- Academic Unit
- Iowa Neuroscience Institute; Pathology
- Record Identifier
- 9984353410002771
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