Abstract 19664: Pharmacological Induction of Torpor/Hypothermia as a Novel Strategy for Improving Cardiac Arrest Resuscitation Outcomes
Introduction: Torpor is the process by which some small species of animals induce a state of hypo-metabolism/hypothermia by decreasing their metabolic rate in order to increase their chances of survival during periods of increased environmental stress. Recently it has been demonstrated that a state of torpor can be induced rapidly and reversibly by 5’adenosine monophosphate (5’AMP) injection in mice. We hypothesized that torpor induction by 5’AMP is a promising therapy for reducing ischemic cellular injury and improving survival following sudden cardiac arrest.
Methods and Results: C57BL/6 wild type mice injected intraperitoneal with 0.5 mg/g or 0.7 mg/g 5’AMP demonstrated a rapid lowering of core body temperature from 37°C to 32°C within 20 minutes and reached a nadir of 28°C by 60 minutes. The duration of this effect was dose dependent lasting 2.5 hours (0.5 mg/g) and 3.5 hours (0.7 mg/g). Mice remained awake but were lethargic during this time, showed no ill effects, and completely recovered following treatment. Next, we tested 5’AMP pre-treatment in a murine model of asystolic cardiac arrest. Anesthetized and ventilated adult female C57BL/6 wild-type mice were injected 30 min prior to cardiac arrest (CA) with 5’AMP or PBS (control). Mice underwent a 16 min KCl-induced CA followed by cardiopulmonary resuscitation. 5’AMP (0.5mg/g) treated mice demonstrated improved myocardial function (%Fractional Shortening (%FS), 45% vs. 28%) and increased survival (100% vs. 30% at 2 hours, n=10, p<0.01). 5’AMP also improved myocardial function and survival when administered at the time of cardiopulmonary resuscitation following a 12 min CA. Unexpectedly, core body temperatures of mice following CA were not significantly different between the two groups at 1hour post-CA, indicating the protective effects of 5’AMP may be independent of its effects on temperature.
Conclusions: Induction of torpor by 5’AMP is protective against ischemic injury and improves survival following sudden cardiac arrest. Torpor induction is promising as a therapeutic strategy for improving post-cardiac arrest outcomes.
Author Disclosures: W.W. Sharp: None. L. Piao: None. Y. Fang: None.
- © 2016 by American Heart Association, Inc.