Histopathological and behavioral characterization of a novel model of cardiac arrest and cardiopulmonary resuscitation in mice

Cardiac arrest is associated with high mortality and poor neurological outcome. We characterized functional and histological outcome in a novel mouse model of cardiac arrest and cardiopulmonary resuscitation (CPR) in order to study neuroprotective mechanisms. Cardiac arrest was induced in male C57Bl/6 and 129SVEV mice by i.v. injection of KCl. After 10 min cardiac standstill, CPR was initiated by administration of epinephrine, ventilation with 100% oxygen and chest compressions. Twenty-four hours before and 3 or 7 days after CPR, mice were subjected to behavioral testing using a passive avoidance task, locomotor activity in an open field, and spontaneous alternation in a T-maze. Hippocampal and caudoputamen injury was quantified 3 or 7 days after CPR. At both time points, caudoputamen injury was worse in 129SVEV mice. Post-ischemic mice of both strains showed a reduced number of correct choices in the T-maze up to 7 days after CPR, and were temporarily impaired in learning the passive avoidance task with a retention deficit on day 3 but not on day 7. Locomotor activity showed strain differences with C57Bl/6 mice being more active, but little ischemia-related effects. A dissociation between functional and histological outcome was found emphasizing the importance of combining both outcome measures for evaluation of neuroprotective strategies.