Abstract 12475: Mechanisms of Akt1-mediated Hypothermia Protection After Cardiac Arrest: Metabolism, Inflammation and Contractile Function
Introduction: Induction of intra-arrest cooling (IC) improves cardiac, neurological and survival outcomes in preclinical models of cardiac arrest. Previous studies demonstrate that IC protection is mediated by Akt1 activation through initiating survival signaling.
Hypothesis: We hypothesize that IC-induced Akt1 activation modulates protective calcium cycling proteins, metabolic, and inflammatory pathways.
Methods: Adult female Akt1+/- underwent 8 min of KCl-induced asystolic arrest and were randomized to receive IC (30 ± 0.5°C) or normothermia (NT) before CPR (n = 10 per group). 72 h survival and mean blood pressure (MAP) were measured. Indicators of glucose utilization, inflammatory responses and contractile function in heart and brain of Akt1+/+ and Akt1+/- mice were assessed (n=5 per group).
Results: No difference on survival was seen for IC and NT treated Akt1+/- mice. IC induced transient improvement in MAP at 30 min following resuscitation (53.6 ± 2.2 vs 71.2 ± 2.6 mmHg p<0.05) and increased phospholamban phosphorylation in the heart of Akt1+/+ mice which were not seen in Akt1+/- mice. Compared to IC-treated Akt1+/+, pyruvate dehydrogenase phosphorylation and sorbitol accumulation were significantly increased, and NAD and ATP contents were markedly reduced in the hearts and brains of Akt1+/- mice. IC significantly inhibited IκBα degradation and NF-κB nuclear translocation, and reduced concentrations of blood lactate and Pre-B cell Colony Enhancing Factor in Akt1+/+ mice, but not Akt1+/- mice.
Conclusion: Akt1 is a critical mediator for TH protection during early post resuscitation in heart and brain through regulating calcium regulatory proteins, enhancing glucose utilization and downregulating inflammatory responses.
Author Disclosures: J. Li: None. H. Wang: None. C. Lee: None. S. Chen: None. X. Zhu: None. Y. Qian: None. R.H. Bunney: None. D.G. Beiser: None. T.L. Vanden Hoek: None.
- © 2016 by American Heart Association, Inc.