Abstract 55: Intra-arrest Hypothermia Fails to Improve Long-Term Survival and Neurological Outcomes in Akt1-Deficient Mice Following Resuscitation
INTRODUCTION: In a mouse model of cardiac arrest, we have previously demonstrated that intra-arrest hypothermia (IH), cooling the body to 30 - 32°C, improves cardiac function and long-term neurologically intact survival rates in C57Bl/6J, wild-type (WT), mice following return of spontaneous circulation (ROSC). Heart Akt is also activated by IH at 4 h post-ROSC. By contrast, IH does not improve post-ROSC cardiac function or increase cardiac Akt activity in Akt1 deficient (Akt1+/-) mice. However, the effect of IH on long-term outcomes in Akt1+/- is unknown.
METHODS: Anesthetized adult female (n = 20) Akt1+/- mice underwent 8 min of KCl-induced asystolic cardiac arrest. After 6 min, mice were randomized to continued normothermia (NT, 37°C) or IH (30°C) followed by re-warming to 37°C at 60 min post-ROSC. Following ROSC, animals were ventilated and invasively monitored for 2 h. At 2 h, vascular catheters were removed, wounds surgically closed, and animals were weaned from positive pressure ventilation over 4 h. Neurologic assessments were performed at regular intervals over 72 h.
RESULTS: NT and IH groups were hemodynamically similar at baseline, during CPR, and at 2 h post-ROSC. ROSC rates were similar in the NT and IH groups (9/10 vs. 10/10, p=0.30). Survival rates (see figure) and neurologic function scores were similar between treatment groups at 6 h, 24 h, and 72 h.
CONCLUSION: The loss of an Akt1 allele abrogates long-term therapeutic benefits of IH in a mouse model of cardiac arrest. These results suggest that Akt1 signaling may play an important role in IH protection.
- © 2011 by American Heart Association, Inc.