Journal article
Transcriptome and metabolome after porcine hemodynamic-directed CPR compared with standard CPR and sham controls
Resuscitation plus, Vol.10, p.100243
06/01/2022
DOI: 10.1016/j.resplu.2022.100243
PMCID: PMC9111986
PMID: 35592874
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 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.
Details
- Title: Subtitle
- Transcriptome and metabolome after porcine hemodynamic-directed CPR compared with standard CPR and sham controls
- Creators
- Kumaran Senthil - University of PennsylvaniaMarco M. Hefti - University of IowaLarry N. Singh - University of PennsylvaniaRyan W. Morgan - University of PennsylvaniaConstantine D. Mavroudis - University of PennsylvaniaTiffany Ko - University of PennsylvaniaHunter Gaudio - University of PennsylvaniaVinay M. Nadkarni - University of PennsylvaniaJohannes Ehinger - Lund University, Mitochondrial Medicine, Sweden; Skåne University Hospital, Department of Otorhinolaryngology, Head and Neck Surgery, SwedenRobert A. Berg - University of PennsylvaniaRobert M. Sutton - University of PennsylvaniaFrancis X. McGowan - University of PennsylvaniaTodd J. Kilbaugh - University of Pennsylvania
- Resource Type
- Journal article
- Publication Details
- Resuscitation plus, Vol.10, p.100243
- DOI
- 10.1016/j.resplu.2022.100243
- PMID
- 35592874
- PMCID
- PMC9111986
- NLM abbreviation
- Resusc Plus
- ISSN
- 2666-5204
- eISSN
- 2666-5204
- Publisher
- Elsevier
- Language
- English
- Date published
- 06/01/2022
- Academic Unit
- Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984258560202771
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