Novel Modification of Potassium Chloride Induced Cardiac Arrest Model for Aged Mice
Liu Huaqin1,2, Yu Zhui1,3, Li Ying1,4, Xu Bin1,5, Yan Baihui1,6, Paschen Wulf1, Warner David S1, Yang Wei1, Sheng Huaxin1,*
1The Multidisciplinary Neuroprotection Laboratories, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA 2Department of Anesthesiology, The 4th Hospital of Hebei Medical University, Shijiazhuang, China 3Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China 4Department of Cardiology, The 5th Hospital of Tianjin, Tianjin, China 5Department of Environmental Health, China Medical University, Shenyang, China 6Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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.
Figure 1. Diagram of the modified mouse cardiac arrest model
The difference from other models is that blood was withdrawn from jugular vein before onset of cardiac arrest to enable use of a small amount of KCl (30 µl 0.5 M) to induce cardiac arrest. Blood was re-infused 3 minutes following cardiac arrest onset. LDF = laser Doppler flow, MAP = mean arterial blood pressure and EKG = electrocardiography.
Figure 2. Electrocardiography (EKG) and mean arterial blood pressure (MAP) changes in cardiac arrest
(A) pre-injury phase, (B) cardiac arrest onset, (C) initial resuscitation phase (D) resuscitation phase with absent blood pressure, (E) late resuscitation phase, (F) recovery phase following resuscitation. For the x-axis in A-F, each square = 0.25 sec.
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