Kumaran Senthil, Marco M Hefti, Larry N Singh, Ryan W Morgan, Constantine D Mavroudis, Tiffany Ko, Hunter Gaudio, Vinay M Nadkarni, Johannes Ehinger, Robert A Berg, Robert M Sutton, Francis X McGowan, Todd J Kilbaugh
Resuscitation plus 2022 JunThe 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. Randomized pre-clinical animal trial. Large animal resuscitation laboratory at an academic children's hospital. Four-week-old female piglets (8-11 kg). 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. 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. 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. IAC 16-001023. © 2022 The Author(s).
Kumaran Senthil, Marco M Hefti, Larry N Singh, Ryan W Morgan, Constantine D Mavroudis, Tiffany Ko, Hunter Gaudio, Vinay M Nadkarni, Johannes Ehinger, Robert A Berg, Robert M Sutton, Francis X McGowan, Todd J Kilbaugh. Transcriptome and metabolome after porcine hemodynamic-directed CPR compared with standard CPR and sham controls. Resuscitation plus. 2022 Jun;10:100243
PMID: 35592874
View Full Text