This Article Full Text Full Text (PDF) All Versions of this Article: 109/22/2786    most recent 01.CIR.0000131940.19833.85v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abella, B. S. Articles by Becker, L. B. Search for Related Content PubMed PubMed Citation Articles by Abella, B. S. Articles by Becker, L. B. Related Collections Animal models of human disease Ischemic biology - basic studies CPR and emergency cardiac care

(Circulation. 2004;109:2786-2791.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Intra-Arrest Cooling Improves Outcomes in a Murine Cardiac Arrest Model

Benjamin S. Abella, MD, MPhil; Danhong Zhao, MD, PhD; Jason Alvarado, BA; Kim Hamann, PhD; Terry L. Vanden Hoek, MD; Lance B. Becker, MD

From the Emergency Resuscitation Center, Section of Emergency Medicine (B.S.A., D.Z., J.A., T.L.V.H., L.B.B.), and the Section of Pulmonary and Critical Care, Department of Medicine (K.H.), The University of Chicago, Chicago, Ill.

Correspondence to Lance B. Becker, MD, Section of Emergency Medicine-MC 5068, The University of Chicago Hospitals, 5841 S Maryland Ave, Chicago, IL 60637. E-mail lbecker{at}medicine.bsd.uchicago.edu

Received April 3, 2003; de novo received November 13, 2003; revision received February 19, 2004; accepted February 25, 2004.

Background— Recent clinical studies have demonstrated that hypothermia to 32° to 34°C provides significant clinical benefit when induced after resuscitation from cardiac arrest. However, cooling during the postresuscitation period was slow, requiring 4 to 8 hours to achieve target temperatures after return of spontaneous circulation (ROSC). Whether more rapid cooling would further improve survival remains unclear. We sought to determine whether cooling during cardiac arrest before ROSC (ie, "intra-arrest" hypothermia) has survival benefit over more delayed post-ROSC cooling, using a murine cardiac arrest model.

Methods and Results— A model of potassium-induced cardiac arrest was established in C57BL/6 mice. After 8 minutes of untreated cardiac arrest, resuscitation was attempted with chest compression, ventilation, and intravenous fluid. Mice were randomized to 3 treatment groups (n=10 each): an intra-arrest hypothermia group, in which mice were cooled to 30°C just before attempted resuscitation, and then rewarmed after 1 hour; a post-ROSC hypothermia group, in which mice were kept at 37°C for 20 minutes after successful ROSC and then were cooled to 30°C for 1 hour; and a normothermic control group, in which mice were kept at 37°C. The intra-arrest hypothermia group demonstrated better 72-hour survival than delayed hypothermia and normothermia groups (6/10 versus 1/10 and 1/10 survivors, respectively, P<0.05), with similar differences seen at 6-hour survival and on neurological scoring.

Conclusions— Timing of hypothermia is a crucial determinant of survival in the murine arrest model. Early intra-arrest cooling appears to be significantly better than delayed post-ROSC cooling or normothermic resuscitation.

Key Words: cardiopulmonary resuscitation • heart arrest • death, sudden • circulation

This article has been cited by other articles:

				M.-S. Tsai, D. Barbut, W. Tang, H. Wang, J. Guan, T. Wang, S. Sun, B. Inderbitzen, and M. H. Weil Rapid Head Cooling Initiated Coincident With Cardiopulmonary Resuscitation Improves Success of Defibrillation and Post-Resuscitation Myocardial Function in a Porcine Model of Prolonged Cardiac Arrest J. Am. Coll. Cardiol., May 20, 2008; 51(20): 1988 - 1990. [Full Text] [PDF]

				F. Kim, M. Olsufka, W.T. Longstreth Jr, C. Maynard, D. Carlbom, S. Deem, P. Kudenchuk, M. K. Copass, and L. A. Cobb Pilot Randomized Clinical Trial of Prehospital Induction of Mild Hypothermia in Out-of-Hospital Cardiac Arrest Patients With a Rapid Infusion of 4{degrees}C Normal Saline Circulation, June 19, 2007; 115(24): 3064 - 3070. [Abstract] [Full Text] [PDF]

				Z.-H. Shao, W.-T. Chang, K. C. Chan, K. R. Wojcik, C.-W. Hsu, C.-Q. Li, J. Li, T. Anderson, Y. Qin, L. B. Becker, et al. Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1995 - H2003. [Abstract] [Full Text] [PDF]

				A. Nozari, P. Safar, S. W. Stezoski, X. Wu, S. Kostelnik, A. Radovsky, S. Tisherman, and P. M. Kochanek Critical Time Window for Intra-Arrest Cooling With Cold Saline Flush in a Dog Model of Cardiopulmonary Resuscitation Circulation, June 13, 2006; 113(23): 2690 - 2696. [Abstract] [Full Text] [PDF]

				V. Srinivasan, V. M. Nadkarni, D. Yannopoulos, B. S. Marino, G. Sigurdsson, S. H. McKnite, M. Zook, D. G. Benditt, and K. G. Lurie Rapid Induction of Cerebral Hypothermia Is Enhanced With Active Compression-Decompression Plus Inspiratory Impedance Threshold Device Cardiopulmonary Resusitation in a Porcine Model of Cardiac Arrest J. Am. Coll. Cardiol., February 21, 2006; 47(4): 835 - 841. [Abstract] [Full Text] [PDF]

				Part 4: Advanced Life Support Circulation, November 29, 2005; 112(22_suppl): III-25 - III-54. [Full Text] [PDF]

				F. Kim, M. Olsufka, D. Carlbom, S. Deem, W.T. Longstreth Jr, M. Hanrahan, C. Maynard, M. K. Copass, and L. A. Cobb Pilot Study of Rapid Infusion of 2 L of 4{degrees}C Normal Saline for Induction of Mild Hypothermia in Hospitalized, Comatose Survivors of Out-of-Hospital Cardiac Arrest Circulation, August 2, 2005; 112(5): 715 - 719. [Abstract] [Full Text] [PDF]

				K. A. Boddicker, Y. Zhang, M. B. Zimmerman, L. R. Davies, and R. E. Kerber Hypothermia Improves Defibrillation Success and Resuscitation Outcomes From Ventricular Fibrillation Circulation, June 21, 2005; 111(24): 3195 - 3201. [Abstract] [Full Text] [PDF]