Abstract
Experimental cardiac arrest (CA) in aging research is infrequently studied in part due to the limitation of animal models. We aimed to develop an easily performed mouse CA model to meet this need. A standard mouse KCl-induced CA model using chest compressions and intravenous epinephrine for resuscitation was modified by blood withdrawal prior to CA onset, so as to decrease the requisite KCl dose to induce CA by decreasing the circulating blood volume. The modification was then compared to the standard model in young adult mice subjected to 8 min CA. 22-month old mice were then subjected to 8 min CA, resuscitated, and compared to young adult mice. Post-CA functional recovery was evaluated by measuring spontaneous locomotor activity pre-injury, and on post-CA days 1, 2, and 3. Neurological score and brain histology were examined on day 3. Brain elF2α phosphorylation levels were measured at 1 h to verify tissue stress. Compared to the standard model, the modification decreased cardiopulmonary resuscitation duration and increased 3-day survival in young mice. For aged mice, survival was 100 % at 24 h and 54% at 72 h. Neurological deficit was present 3 days post-CA, although more severe versus young mice. Mild neuronal necrosis was present in the cortex and hippocampus. The modified model markedly induced elF2α phosphorylation in both age groups. This modified procedure makes the CA model feasible in aged mice and provides a practical platform for understanding injury mechanisms and developing therapeutics for elderly patients.
Highlights
The American Heart Association reports that there are >350,000 cases of cardiac arrest (CA) per year in the United States, accounting for 50% of all cardiovascular deaths [1]
This study was approved by the Duke University Animal Care and Use Committee, and complied with the Guide for the Care and Use of Animals published by the National Institutes of Health. 8-10-week old and 22-month old male C57Bl/6 mice were purchased from Jackson Laboratory and the National Institute on Aging
All mice were successfully resuscitated from 8 min CA
Summary
The American Heart Association reports that there are >350,000 cases of cardiac arrest (CA) per year in the United States, accounting for 50% of all cardiovascular deaths [1]. Clinical investigations recently analyzed factors associated with outcome and long-term survival in elderly patients with out-of-hospital CA [3,4,5,6], as well as the effect of age on survival and outcome [7, 8]. Cardiac arrest model for aged mice therapy to improve clinical outcome. Compared to 3-6-month-old rats, overall survival rate, hypoxic ventilatory response, and brain mitochondrial respiratory function were decreased in 24-month old rats following CA and resuscitation, while hippocampal CA1 injury was increased [15]. A major factor discouraging investigators from using aged animal models is poor post-CA survival [18]. The purpose of this study was to develop an improved CA model in aged mice to address this limitation
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