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Transcriptome and metabolome after porcine hemodynamic-directed CPR compared with standard CPR and sham controls

Senthil, Kumaran ; Hefti, Marco M. ; Singh, Larry N. ; Morgan, Ryan W. ; Mavroudis, Constantine D. ; Ko, Tiffany ; Gaudio, Hunter ; Nadkarni, Vinay M. ; Ehinger, Johannes LU orcid and Berg, Robert A. , et al. (2022) In Resuscitation Plus 10.
Abstract

Objective: The effect of cardiac arrest (CA) on cerebral transcriptomics and metabolomics is unknown. We previously demonstrated hemodynamic-directed CPR (HD-CPR) improves survival with favorable neurologic outcomes versus standard CPR (Std-CPR). We hypothesized HD-CPR would preserve the cerebral transcriptome and metabolome compared to Std-CPR. Design: Randomized pre-clinical animal trial. Setting: Large animal resuscitation laboratory at an academic children's hospital. Subjects: Four-week-old female piglets (8–11 kg). Interventions: Pigs (1-month-old), three groups: 1) HD-CPR (compression depth to systolic BP 90 mmHg, vasopressors to coronary perfusion pressure 20 mmHg); 2) Std-CPR and 3) shams (no CPR). HD-CPR and Std-CPR underwent... (More)

Objective: The effect of cardiac arrest (CA) on cerebral transcriptomics and metabolomics is unknown. We previously demonstrated hemodynamic-directed CPR (HD-CPR) improves survival with favorable neurologic outcomes versus standard CPR (Std-CPR). We hypothesized HD-CPR would preserve the cerebral transcriptome and metabolome compared to Std-CPR. Design: Randomized pre-clinical animal trial. Setting: Large animal resuscitation laboratory at an academic children's hospital. Subjects: Four-week-old female piglets (8–11 kg). Interventions: Pigs (1-month-old), three groups: 1) HD-CPR (compression depth to systolic BP 90 mmHg, vasopressors to coronary perfusion pressure 20 mmHg); 2) Std-CPR and 3) shams (no CPR). HD-CPR and Std-CPR underwent asphyxia, induced ventricular fibrillation, 10–20 min of CPR and post-resuscitation care. Primary outcomes at 24 h in cerebral cortex: 1) transcriptomic analysis (n = 4 per treatment arm, n = 8 sham) of 1727 genes using differential gene expression and 2) metabolomic analysis (n = 5 per group) of 27 metabolites using one-way ANOVA, post-hoc Tukey HSD. Measurements and main results: 65 genes were differentially expressed between HD-CPR and Std-CPR and 72 genes between Std-CPR and sham, but only five differed between HD-CPR and sham. Std-CPR increased the concentration of five AA compared to HD-CPR and sham, including the branched chain amino acids (BCAA), but zero metabolites differed between HD-CPR and sham. Conclusions: In cerebral cortex 24 h post CA, Std-CPR resulted in a different transcriptome and metabolome compared with either HD-CPR or sham. HD-CPR preserves the transcriptome and metabolome, and is neuroprotective. Global molecular analyses may be a novel method to assess efficacy of clinical interventions and identify therapeutic targets. Institutional protocol number: IAC 16-001023.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiac arrest, Cardiopulmonary resuscitation, Metabolomics, RNA sequence, Transcriptome
in
Resuscitation Plus
volume
10
article number
100243
publisher
Elsevier
external identifiers
  • scopus:85129817500
  • pmid:35592874
ISSN
2666-5204
DOI
10.1016/j.resplu.2022.100243
language
English
LU publication?
yes
id
512da4df-60c1-4799-a7ad-4789f3655cda
date added to LUP
2022-09-02 15:14:08
date last changed
2024-05-29 18:28:45
@article{512da4df-60c1-4799-a7ad-4789f3655cda,
  abstract     = {{<p>Objective: The effect of cardiac arrest (CA) on cerebral transcriptomics and metabolomics is unknown. We previously demonstrated hemodynamic-directed CPR (HD-CPR) improves survival with favorable neurologic outcomes versus standard CPR (Std-CPR). We hypothesized HD-CPR would preserve the cerebral transcriptome and metabolome compared to Std-CPR. Design: Randomized pre-clinical animal trial. Setting: Large animal resuscitation laboratory at an academic children's hospital. Subjects: Four-week-old female piglets (8–11 kg). Interventions: Pigs (1-month-old), three groups: 1) HD-CPR (compression depth to systolic BP 90 mmHg, vasopressors to coronary perfusion pressure 20 mmHg); 2) Std-CPR and 3) shams (no CPR). HD-CPR and Std-CPR underwent asphyxia, induced ventricular fibrillation, 10–20 min of CPR and post-resuscitation care. Primary outcomes at 24 h in cerebral cortex: 1) transcriptomic analysis (n = 4 per treatment arm, n = 8 sham) of 1727 genes using differential gene expression and 2) metabolomic analysis (n = 5 per group) of 27 metabolites using one-way ANOVA, post-hoc Tukey HSD. Measurements and main results: 65 genes were differentially expressed between HD-CPR and Std-CPR and 72 genes between Std-CPR and sham, but only five differed between HD-CPR and sham. Std-CPR increased the concentration of five AA compared to HD-CPR and sham, including the branched chain amino acids (BCAA), but zero metabolites differed between HD-CPR and sham. Conclusions: In cerebral cortex 24 h post CA, Std-CPR resulted in a different transcriptome and metabolome compared with either HD-CPR or sham. HD-CPR preserves the transcriptome and metabolome, and is neuroprotective. Global molecular analyses may be a novel method to assess efficacy of clinical interventions and identify therapeutic targets. Institutional protocol number: IAC 16-001023.</p>}},
  author       = {{Senthil, Kumaran and Hefti, Marco M. and Singh, Larry N. and Morgan, Ryan W. and Mavroudis, Constantine D. and Ko, Tiffany and Gaudio, Hunter and Nadkarni, Vinay M. and Ehinger, Johannes and Berg, Robert A. and Sutton, Robert M. and McGowan, Francis X. and Kilbaugh, Todd J.}},
  issn         = {{2666-5204}},
  keywords     = {{Cardiac arrest; Cardiopulmonary resuscitation; Metabolomics; RNA sequence; Transcriptome}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Resuscitation Plus}},
  title        = {{Transcriptome and metabolome after porcine hemodynamic-directed CPR compared with standard CPR and sham controls}},
  url          = {{http://dx.doi.org/10.1016/j.resplu.2022.100243}},
  doi          = {{10.1016/j.resplu.2022.100243}},
  volume       = {{10}},
  year         = {{2022}},
}