Transcriptome and metabolome after porcine hemodynamic-directed CPR compared with standard CPR and sham controls.
Resusc Plus
; 10: 100243, 2022 Jun.
Article
em En
| MEDLINE
| ID: mdl-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 mainresults:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Clinical_trials
/
Guideline
Idioma:
En
Revista:
Resusc Plus
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos