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.

Deciphering of Mitochondrial Cardiolipin Oxidative Signaling in Cerebral Ischemia-Reperfusion

“…We assessed motor function with the well-established beam balance and inclined platform tests and evaluated cognitive performance using Morris water maze task, which are sensitive to motor and cognitive dysfunction after CA. 21 There were no statistically significant differences between the two sham groups thus they were pooled into one group for analysis. Balancing ability or inclined platform performance did not differ among groups before surgery ( Figures 8A and 8B).…”

Polynitroxyl Albumin and Albumin Therapy after Pediatric Asphyxial Cardiac Arrest: Effects on Cerebral Blood Flow and Neurologic Outcome

“…Further studies are required before a definitive conclusion can be drawn regarding the influence of blunting or augmenting early hyperemia on neuronal death. We selected the CA 1 hippocampus given its vulnerability in this model and the capacity to quantify neuronal counts through stereology (Fink et al, 2005). Quantification of neuronal death in other anatomic areas after CA is warranted.…”

“…We assessed the ability of rats to balance on a suspended, narrow wooden beam for 60 seconds (beam balance test). We measured the maximum angle (45 to 851) at which the rat maintained its position on an inclined plane for 10 seconds (inclined plane test) (Fink et al, 2005). We tested spatial memory acquisition and retention using the Morris water maze on days 7 to 14 after asphyxia or sham surgery.…”

Brain Resuscitation in the Drowning Victim

“…Several therapies have shown promise in this model, e.g., mild hypothermia, glucose and insulin, and neurotensin [223,[226][227][228][229]. There also are pediatric analogs [230][231][232][233], which use post-natal Day 17 rats. Promising results have been obtained with hypothermia and minocycline [231,233].…”

“…There also are pediatric analogs [230][231][232][233], which use post-natal Day 17 rats. Promising results have been obtained with hypothermia and minocycline [231,233]. Mouse ACA models have not been developed.…”