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Published on: May 21, 2019
Transcriptome and metabolome after porcine hemodynamic-directed CPR compared with standard CPR and sham controls
Kumaran Senthil1, Marco M Hefti2, Larry N Singh1
1Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Department of Anesthesiology and Critical Care Medicine, United States.
Insights
Hemodynamic-directed CPR (HD-CPR) preserves brain gene expression and metabolites after cardiac arrest compared to standard CPR. This neuroprotective effect suggests HD-CPR may be a superior resuscitation strategy.
Area of Science:
- Neuroscience
- Biochemistry
- Cardiology
Background:
- Cardiac arrest (CA) impacts cerebral transcriptomics and metabolomics.
- Hemodynamic-directed CPR (HD-CPR) shows improved survival and neurologic outcomes over standard CPR (Std-CPR).
Purpose of the Study:
- To investigate the effect of HD-CPR versus Std-CPR on cerebral transcriptomics and metabolomics post-cardiac arrest.
- To determine if HD-CPR preserves brain molecular profiles compared to Std-CPR.
Main Methods:
- A randomized pre-clinical animal trial using 1-month-old piglets.
- Three groups: HD-CPR, Std-CPR, and sham (no CPR).
- Analysis of cerebral cortex transcriptomics (1727 genes) and metabolomics (27 metabolites) 24 hours post-resuscitation.
Main Results:
- Std-CPR altered the cerebral transcriptome and metabolome compared to both HD-CPR and sham groups.
- 65 genes differed between HD-CPR and Std-CPR; 72 genes between Std-CPR and sham; only 5 between HD-CPR and sham.
- Std-CPR increased specific amino acids, including branched-chain amino acids (BCAA), unlike HD-CPR.
Conclusions:
- HD-CPR preserves the cerebral transcriptome and metabolome 24 hours after cardiac arrest.
- HD-CPR demonstrates neuroprotective effects, suggesting its superiority over Std-CPR.
- Global molecular analyses can assess intervention efficacy and identify therapeutic targets in resuscitation.
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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