Experimental model of pediatric asphyxial cardiopulmonary arrest in rats

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Abstract
Objective Develop a clinically relevant model of pediatric asphyxial cardiopulmonary arrest in rats. Design Prospective interventional study. Setting University research laboratory. Subjects Postnatal day 16–18 rats (n = 9/group). Interventions Anesthetized rats were endotracheally intubated and mechanically ventilated, and vascular catheters were inserted. Vecuronium was administered, and the ventilator was disconnected from the rats for 8 mins, whereupon rats were resuscitated with epinephrine, sodium bicarbonate, and chest compressions until spontaneous circulation returned. Shams underwent all procedures except asphyxia. Measurements and Main Results Asphyxial arrest typically occurred by 1 min after the ventilator was disconnected. Return of spontaneous circulation typically occurred p < .05). Spatial memory acquisition measured using the Morris-water maze on days 7–14 and 28–35 was also impaired in rats after asphyxia vs. sham injury (total latency 379 ± 28 vs. 501 ± 40 secs, respectively, p < .05). DNA fragmentation was detected in CA1 hippocampal neurons bilaterally 3–7 days after asphyxia. Neurodegeneration detected using Fluorojade B was seen in bilateral CA1 hippocampi and layer V cortical neurons 3–7 days after asphyxia, with persistent neurodegeneration in CA1 hippocampus detected up to 5 wks after asphyxia. CA1 hippocampal neuron survival after asphyxia was 39–43% (p < .001 vs. sham). Evidence of DNA or cellular injury was not detected in sham rats. Conclusions This model of asphyxial cardiopulmonary arrest in postnatal day 17 rats produces many of the clinical manifestations of pediatric hypoxic-ischemic encephalopathy. This model may be useful for the preclinical testing of novel and currently available interventions aimed at improving neurologic outcome in infants and children after cardiopulmonary arrest.