Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and Disease    2018, Vol. 9 Issue (1) : 31-39     DOI: 10.14336/AD.2017.0221
Orginal Article |
Novel Modification of Potassium Chloride Induced Cardiac Arrest Model for Aged Mice
Huaqin Liu1,2,Zhui Yu1,3,Ying Li1,4,Bin Xu1,5,Baihui Yan1,6,Wulf Paschen1,David S Warner1,Wei Yang1,Huaxin Sheng1,*
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
Download: PDF(1158 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    

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.

Keywords cardiac arrest      resuscitation      mouse model      aging     
Corresponding Authors: Huaxin Sheng   
Issue Date: 01 February 2018
E-mail this article
E-mail Alert
Articles by authors
Huaqin Liu
Zhui Yu
Ying Li
Bin Xu
Baihui Yan
Wulf Paschen
David S Warner
Wei Yang
Huaxin Sheng
Cite this article:   
Huaqin Liu,Zhui Yu,Ying Li, et al. Novel Modification of Potassium Chloride Induced Cardiac Arrest Model for Aged Mice[J]. A&D, 2018, 9(1): 31-39.
URL:     OR
[1] Patil KD, Halperin HR, Becker LB (2015). Cardiac arrest: resuscitation and reperfusion. Circ Res, 116:2041-9.
[2] Becker LB, Han BH, Meyer PM, Wright FA, Rhodes KV, Smith DW,et al. (1993). Racial differences in the incidence of cardiac arrest and subsequent survival. The CPR Chicago Project. N Engl J Med, 329:600-6.
[3] Group S-KS (2015). Changes in treatments and outcomes among elderly patients with out-of-hospital cardiac arrest between 2002 and 2012: A post hoc analysis of the SOS-KANTO 2002 and 2012. Resuscitation, 97:76-82.
[4] Churpek MM, Yuen TC, Winslow C, Hall J, Edelson DP (2015). Differences in vital signs between elderly and nonelderly patients prior to ward cardiac arrest. Crit Care Med, 43:816-22.
[5] Grimaldi D, Dumas F, Perier MC, Charpentier J, Varenne O, Zuber B,et al. (2014). Short- and long-term outcome in elderly patients after out-of-hospital cardiac arrest: a cohort study. Crit Care Med, 42:2350-7.
[6] Kitamura T, Morita S, Kiyohara K, Nishiyama C, Kajino K, Sakai T,et al. (2014). Trends in survival among elderly patients with out-of-hospital cardiac arrest: a prospective, population-based observation from 1999 to 2011 in Osaka. Resuscitation, 85:1432-8.
[7] Sandroni C, Caricato A (2014). Outcomes in elderly patients resuscitated from cardiac arrest: is age an independent predictor?. Crit Care Med, 42:453-4.
[8] Van Hoeyweghen RJ, Bossaert LL, Mullie A, Martens P, Delooz HH, Buylaert WA,et al. (1992). Survival after out-of-hospital cardiac arrest in elderly patients. Belgian Cerebral Resuscitation Study Group. Ann Emerg Med, 21:1179-84.
[9] Reynolds JC, Frisch A, Rittenberger JC, Callaway CW (2013). Duration of resuscitation efforts and functional outcome after out-of-hospital cardiac arrest: when should we change to novel therapies?. Circulation, 128:2488-94.
[10] Xu Y, Liachenko SM, Tang P, Chan PH (2009). Faster recovery of cerebral perfusion in SOD1-overexpressed rats after cardiac arrest and resuscitation. Stroke, 40:2512-8.
[11] Zoerner F, Wiklund L, Miclescu A, Martijn C (2013). Therapeutic hypothermia activates the endothelin and nitric oxide systems after cardiac arrest in a pig model of cardiopulmonary resuscitation. PLoS One, 8:e64792.
[12] Zhao D, Abella BS, Beiser DG, Alvarado JP, Wang H, Hamann KJ,et al. (2008) Intra-arrest cooling with delayed reperfusion yields higher survival than earlier normothermic resuscitation in a mouse model of cardiac arrest. Resuscitation, 77:242-9.
[13] Vasileiou PV, Xanthos T, Barouxis D, Pantazopoulos C, Papalois AE, Lelovas P,et al. (2014). Erythropoietin administration facilitates return of spontaneous circulation and improves survival in a pig model of cardiac arrest. Am J Emerg Med, 32:871-7.
[14] Xu K, Puchowicz MA, LaManna JC (2016). Aging Effect on Post-recovery Hypofusion and Mortality Following Cardiac Arrest and Resuscitation in Rats. Adv Exp Med Biol, 876:265-70.
[15] Xu K, Puchowicz MA, Sun X, LaManna JC (2010). Decreased brainstem function following cardiac arrest and resuscitation in aged rat. Brain Res, 1328:181-9.
[16] Ikeda M, Swide T, Vayl A, Lahm T, Anderson S, Hutchens MP (2015). Estrogen administered after cardiac arrest and cardiopulmonary resuscitation ameliorates acute kidney injury in a sex- and age-specific manner. Crit Care, 19:332.
[17] Fisher M, Feuerstein G, Howells DW, Hurn PD, Kent TA, Savitz SI,et al. (2009). Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke, 40:2244-50.
[18] Cohan CH, Neumann JT, Dave KR, Alekseyenko A, Binkert M, Stransky K,et al. (2015). Effect of cardiac arrest on cognitive impairment and hippocampal plasticity in middle-aged rats. PLoS One, 10:e0124918.
[19] Combs DJ, D’Alecy LG (1987). Motor performance in rats exposed to severe forebrain ischemia: effect of fasting and 1,3-butanediol. Stroke, 18:503-11.
[20] Sheng H, Laskowitz DT, Mackensen GB, Kudo M, Pearlstein RD, Warner DS (1999). Apolipoprotein E deficiency worsens outcome from global cerebral ischemia in the mouse. Stroke, 30:1118-24.
[21] Sheng H, Laskowitz DT, Pearlstein RD, Warner DS (1999). Characterization of a recovery global cerebral ischemia model in the mouse. J Neurosci Methods, 88:103-9.
[22] Liu S, Sheng H, Yu Z, Paschen W, Yang W (2016). O-linked beta-n-acetylglucosamine modification of proteins is activated in post-ischemic brains of young but not aged mice: Implications for impaired functional recovery from ischemic stress. J Cereb Blood Flow Metab, 36(2):393-8.
[23] Katz L, Ebmeyer U, Safar P, Radovsky A, Neumar R (1995). Outcome model of asphyxial cardiac arrest in rats. J Cereb Blood Flow Metab, 15:1032-9.
[24] McCaul CL, McNamara PJ, Engelberts D, Wilson GJ, Romaschin A, Redington AN,et al. (2006). Epinephrine increases mortality after brief asphyxial cardiac arrest in an in vivo rat model. Anesth Analg, 102:542-8.
[25] Xiao F, Safar P, Radovsky A (1998). Mild protective and resuscitative hypothermia for asphyxial cardiac arrest in rats. Am J Emerg Med, 16:17-25.
[26] Zhang YE, Fu SZ, Li XQ, Chen P, Wang JL, Che J,et al. (2011). PEP-1-SOD1 protects brain from ischemic insult following asphyxial cardiac arrest in rats. Resuscitation, 82:1081-6.
[27] Hachimi-Idrissi S, Corne L, Huyghens L (2001). The effect of mild hypothermia and induced hypertension on long term survival rate and neurological outcome after asphyxial cardiac arrest in rats. Resuscitation, 49:73-82.
[28] Vaagenes P, Safar P, Moossy J, Rao G, Diven W, Ravi C,et al. (1997). Asphyxiation versus ventricular fibrillation cardiac arrest in dogs. Differences in cerebral resuscitation effects--a preliminary study. Resuscitation, 35:41-52.
[29] Pernat A, Weil MH, Sun S, Tang W, Yamaguchi H, Bisera J (2000). Atrial function during cardiac arrest caused by ventricular fibrillation. Chest, 117:1118-23.
[30] Dave KR, Della-Morte D, Saul I, Prado R, Perez-Pinzon MA (2013). Ventricular fibrillation-induced cardiac arrest in the rat as a model of global cerebral ischemia. Transl Stroke Res, 4:571-8.
[31] Janata A, Magnet IA, Uray T, Stezoski JP, Janesko-Feldman K, Tisherman SA,et al. (2014). Regional TNFalpha mapping in the brain reveals the striatum as a neuroinflammatory target after ventricular fibrillation cardiac arrest in rats. Resuscitation, 85:694-701.
[32] Ikeda K, Liu X, Kida K, Marutani E, Hirai S, Sakaguchi M,et al. (2016). Thiamine as a neuroprotective agent after cardiac arrest. Resuscitation, 105:138-44.
[33] Yang W, Paschen W (2016). Unfolded protein response in brain ischemia: A timely update. J Cereb Blood Flow Metab, 36(12):2044-2050.
[34] Ikeda K, Marutani E, Hirai S, Wood ME, Whiteman M, Ichinose F (2015). Mitochondria-targeted hydrogen sulfide donor AP39 improves neurological outcomes after cardiac arrest in mice. Nitric Oxide, 49:90-6.
[35] Wang J, Fujiyoshi T, Kosaka Y, Raybuck JD, Lattal KM, Ikeda M,et al. (2013). Inhibition of soluble epoxide hydrolase after cardiac arrest/cardiopulmonary resuscitation induces a neuroprotective phenotype in activated microglia and improves neuronal survival. J Cereb Blood Flow Metab, 33:1574-81.
[36] Deng G, Yonchek JC, Quillinan N, Strnad FA, Exo J, Herson PS,et al. (2014). A novel mouse model of pediatric cardiac arrest and cardiopulmonary resuscitation reveals age-dependent neuronal sensitivities to ischemic injury. J Neurosci Methods, 222:34-41.
[37] Teschendorf P, Albertsmeier M, Vogel P, Padosch SA, Spohr F, Kirschfink M,et al. (2008). Neurological outcome and inflammation after cardiac arrest--effects of protein C in rats. Resuscitation, 79:316-24.
[38] Hutchens MP, Kosaka Y, Zhang W, Fujiyoshi T, Murphy S, Alkayed N,et al. (2014). Estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation is robust to GPR30 gene deletion. PLoS One, 9:e99910.
[39] Schmitz B, Bock C, Hoehn-Berlage M, Kerskens CM, Bottiger BW, Hossmann KA (1998). Recovery of the rodent brain after cardiac arrest: a functional MRI study. Magn Reson Med, 39:783-8.
[1] Feng Tang,Meng-Hao Pan,Yujie Lu,Xiang Wan,Yu Zhang,Shao-Chen Sun. Involvement of Kif4a in Spindle Formation and Chromosome Segregation in Mouse Oocytes[J]. A&D, 2018, 9(4): 623-633.
[2] J. Thomas Mock,Sherilynn G Knight,Philip H Vann,Jessica M Wong,Delaney L Davis,Michael J Forster,Nathalie Sumien. Gait Analyses in Mice: Effects of Age and Glutathione Deficiency[J]. A&D, 2018, 9(4): 634-646.
[3] Jiayu Wu,Weiying Ren,Li Li,Man Luo,Kan Xu,Jiping Shen,Jia Wang,Guilin Chang,Yi Lu,Yiming Qi,Binger Xu,Yuting He,Yu Hu. Effect of Aging and Glucagon-like Peptide 2 on Intestinal Microbiota in SD Rats[J]. A&D, 2018, 9(4): 566-577.
[4] Carmen G Vinagre,Fatima R Freitas,Carlos H de Mesquita,Juliana C Vinagre,Ana Carolina Mariani,Roberto Kalil-Filho,Raul C Maranhão. Removal of Chylomicron Remnants from the Bloodstream is Delayed in Aged Subjects[J]. A&D, 2018, 9(4): 748-754.
[5] Aurore Marie,Johann Meunier,Emilie Brun,Susanna Malmstrom,Veronique Baudoux,Elodie Flaszka,Gaëlle Naert,François Roman,Sylvie Cosnier-Pucheu,Sergio Gonzalez-Gonzalez. N-acetylcysteine Treatment Reduces Age-related Hearing Loss and Memory Impairment in the Senescence-Accelerated Prone 8 (SAMP8) Mouse Model[J]. A&D, 2018, 9(4): 664-673.
[6] Yali Chen,Mengmei Yin,Xuejin Cao,Gang Hu,Ming Xiao. Pro- and Anti-inflammatory Effects of High Cholesterol Diet on Aged Brain[J]. A&D, 2018, 9(3): 374-390.
[7] Wenzhi Sun,Jiewen Tan,Zhuo Li,Shibao Lu,Man Li,Chao Kong,Yong Hai,Chunjin Gao,Xuehua Liu. Evaluation of Hyperbaric Oxygen Treatment in Acute Traumatic Spinal Cord Injury in Rats Using Diffusion Tensor Imaging[J]. A&D, 2018, 9(3): 391-400.
[8] Changjun Yang,Kelly M. DeMars,Eduardo Candelario-Jalil. Age-Dependent Decrease in Adropin is Associated with Reduced Levels of Endothelial Nitric Oxide Synthase and Increased Oxidative Stress in the Rat Brain[J]. A&D, 2018, 9(2): 322-330.
[9] Lin-Yuan Zhang,Pan Lin,Jiaji Pan,Yuanyuan Ma,Zhenyu Wei,Lu Jiang,Liping Wang,Yaying Song,Yongting Wang,Zhijun Zhang,Kunlin Jin,Qian Wang,Guo-Yuan Yang. CLARITY for High-resolution Imaging and Quantification of Vasculature in the Whole Mouse Brain[J]. A&D, 2018, 9(2): 262-272.
[10] Weiming Hu,Junwu Wu,Wenjing Jiang,Jianguo Tang. MicroRNAs and Presbycusis[J]. A&D, 2018, 9(1): 133-142.
[11] Barbara Strasser,Konstantinos Volaklis,Dietmar Fuchs,Martin Burtscher. Role of Dietary Protein and Muscular Fitness on Longevity and Aging[J]. A&D, 2018, 9(1): 119-132.
[12] Fangyu Peng,Fang Xie,Otto Muzik. Alteration of Copper Fluxes in Brain Aging: A Longitudinal Study in Rodent Using 64CuCl2-PET/CT[J]. A&D, 2018, 9(1): 109-118.
[13] Nathalie K Zgheib,Fatima Sleiman,Lara Nasreddine,Mona Nasrallah,Nancy Nakhoul,Hussain Isma’eel,Hani Tamim. Short Telomere Length is Associated with Aging, Central Obesity, Poor Sleep and Hypertension in Lebanese Individuals[J]. A&D, 2018, 9(1): 77-89.
[14] Mari L. Sbardelotto,Giulia S. Pedroso,Fernanda T. Pereira,Helen R. Soratto,Stella MS. Brescianini,Pauline S. Effting,Anand Thirupathi,Renata T. Nesi,Paulo CL. Silveira,Ricardo A. Pinho. The Effects of Physical Training are Varied and Occur in an Exercise Type-Dependent Manner in Elderly Men[J]. A&D, 2017, 8(6): 887-898.
[15] Veronika Cakova,Frederic Bonte,Annelise Lobstein. Dendrobium: Sources of Active Ingredients to Treat Age-Related Pathologies[J]. A&D, 2017, 8(6): 827-849.
Full text



Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail:
Powered by Beijing Magtech Co. Ltd