Brief Induced Hypothermia Improves Outcome after Asphyxial Cardiopulmonary Arrest in Juvenile Rats

Abstract

The American Heart Association has endorsed the use of mild hypothermia for adults after cardiopulmonary arrest. However, there are no contemporary trials testing hypothermia in children after cardiopulmonary arrest and extrapolation from adult studies is problematic given differences in brain development and primary etiology (asphyxia in children vs. ventricular arrhythmia in adults). Accordingly, we tested the effects of mild postresuscitative hypothermia on functional and histopathological outcome after asphyxial cardiac arrest in juvenile rats. Postnatal day 17 rats were subjected to 8 min of asphyxia-induced cardiac arrest followed by resuscitation. Rats were randomized to normothermic (37°C), hypothermic (32°C), or unregulated temperature groups (n = 7–8/group) to begin after return of spontaneous circulation for a duration of 1 h. Brain temperature in the unregulated group dropped to 34.0 ± 0.4°C at 1 h. The hypothermic group had improved motor function assessed using beam balance and inclined plane tests vs. the normothermic group. The depth of hypothermia was associated with increased CA1 hippocampal neuron survival at 5 weeks. Neurodegeneration in the CA1 hippocampus assessed using Fluoro-Jade B labeling at 5 weeks was not detected in the 32°C group, whereas 2/7 and 4/7 rats in the 34 and 37°C groups, respectively, showed neurodegeneration. Brief treatment with moderate induced hypothermia improved functional outcome and prevented long-term neurodegeneration in a model that mimics the clinical and histopathological scenario of pediatric cardiac arrest. Similar to adults, infants and children may benefit from induced hypothermia after cardiopulmonary arrest, warranting further study.