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Experimental Hyperthermia during Cardiac Arrest and CPR Is Associated with Severe Spontaneous Hypothermia in Mice

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DOI: 10.4236/nm.2012.33035    3,783 Downloads   5,560 Views   Citations


Background: Since genetically engineered mice are becoming more and more available, these animals become of high interest to study physiologic and pathophysiologic pathways of brain ischemia. The aim of this study was to examine body temperature (Tb), physical activity variation and neurohistopathology in mice exposed to normothermic and hyperthermic cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Methods: Male C57Bl/6 mice weighing 22 - 27 g were implanted intraperitoneally with a radio telemeter and subjected to 10 min cardiac arrest followed by cardiopulmonary resuscitation. Normothermia (37.5°C) or hyperthermia (39.0°C) was induced by controlling pericranial temperature during the arrest period. Results: Hyperthermia during the arrest resulted in a Tb decrease during early recovery to a nadir of 28°C ± 0.8°C (mean ± SE) and partially recovered to 34.4°C ± 1°C 36 hrs after CA/CPR. With normothermia during the arrest, Tb depression was less pronounced (nadir of 32.3°C ± 0.3°C) and recovered to physiologic levels within 24 hrs. Coupling of physical activity and body temperature was absent in all animals after CA/CPR. Neuronal injury in the caudoputamen was greater in the hyperthermia group. Conclusions: This study demonstrates that CA/CPR eliminates normal connectivity between body temperature and physical activity and induces long-lasting hypothermia, the depth of which is related to severity of brain injury. Long term temperature monitoring is required in survival murine experiments, if body temperature is a study variable.

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R. Noppens, J. Kofler and R. Traystman, "Experimental Hyperthermia during Cardiac Arrest and CPR Is Associated with Severe Spontaneous Hypothermia in Mice," Neuroscience and Medicine, Vol. 3 No. 3, 2012, pp. 306-313. doi: 10.4236/nm.2012.33035.


[1] S. A. Bernard and M. Buist, “Induced Hypothermia in Critical Care Medicine: A review,” Critical Care Medicine, Vol. 31, No. 7, 2003, pp. 2041-2051. doi:10.1097/01.CCM.0000069731.18472.61
[2] L. J. Morrison, C. D. Deakin, P. T. Morley, et al., “Part 8: Advanced Life Support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations,” Circulation, Vol. 122, No. 16, 2010, pp. S345-S421. doi:10.1161/CIRCULATIONAHA.110.971051
[3] M. D. Ginsberg and R. Busto, “Combating hyperthermia in Acute Stroke: A Significant Clinical Concern,” Stroke, Vol. 29, No. 2, 1998, pp. 529-534. doi:10.1161/01.STR.29.2.529
[4] D. W. Marion, “Controlled Normothermia in Neurologic Intensive Care,” Critical Care Medicine, Vol. 32, No. 2, 2004, pp. S43-S45. doi:10.1097/01.CCM.0000110731.69637.16
[5] P. A. Barber, L. Hoyte, F. Colbourne and A. M. Buchan, “Temperatureregulated Model of Focal Ischemia in the Mouse: A Study with Histopathological and Behavioral Outcomes,” Stroke, Vol. 35, No. 7, 2004, pp. 1720-1725. doi:10.1161/01.STR.0000129653.22241.d7
[6] F. Li, T. Omae and M. Fisher, “Spontaneous Hyperthermia and Its Mechanism in the Intraluminal Suture Middle Cerebral Artery Occlusion Model of Rats,” Stroke, Vol. 30, No. 11, 1999, pp. 2464-2471. doi:10.1161/01.STR.30.11.2464
[7] Q. Zhao, H. Memezawa, M.-L. Smith and B. K. Siesj?, “Hyperthermia Complicates Middle Cerebral Artery Occlusion Induced by an Intraluminal Filament,” Brain Research, Vol. 649, No. 1-2, 1994, pp. 253-259. doi:10.1016/0006-8993(94)91071-5
[8] R. W. Hickey, H. Ferimer, H. L. Alexander, et al., “Delayed, Spontaneous Hypothermia Reduces Neuronal Damage after Asphyxial Cardiac Arrest in Rats,” Crit Care Medicine, Vol. 28, No. 10, 2000, pp. 3511-3516. doi:10.1097/00003246-200010000-00027
[9] W. C. Plahta, D. L. Clark and F. Colbourne, “17 β-Estradiol Pretreatment Reduces Ca1 Sector Cell Death and the Spontaneous Hyperthermia that Follows Forebrain Ischemia in the Gerbil,” Neuroscience, Vol. 129, No. 1, 2004, pp. 187-193. doi:10.1016/j.neuroscience.2004.07.037
[10] G. Wei and S. Doré, “Importance of Normothermia Control in Investigating Delayed Neuronal Injury in a Mouse Global Ischemia Model,” Journal of Neuroscience Methods, Vol. 185, No. 2, 2010, pp. 230-235. doi:10.1016/j.jneumeth.2009.09.026
[11] J. Kofler, K. Hattori, M. Sawada, et al., “Histopathological and Behavioral Characterization of a Novel Model of Cardiac Arrest and Cardiopulmonary Resuscitation in Mice,” Journal of Neuroscience Methods, Vol. 136, No. 1, 2004, pp. 33-44. doi:10.1016/j.jneumeth.2003.12.024
[12] R. R. Noppens, J. Kofler, M. R. Grafe, P. D. Hurn and R. J. Traystman, “Estradiol after Cardiac Arrest and Cardiopulmonary Resuscitation Is Neuroprotective and Mediated through Estrogen Receptor-β,” Journal of Cerebral Blood Flow & Metabolism, Vol. 29, No. 2, 2009, pp. 277-286. doi:10.1038/jcbfm.2008.116
[13] A. Harkin, T. J. Connor, J. M. O’Donnell and J. P. Kelly, “Physiological and Behavioral Responses to Stress: What Does a Rat Find Stressful?” Lab Animal (NY), Vol. 31, No. 4, 2002, pp. 42-50.
[14] B. A. Rikke, J. E. Yerg, M. E. Battaglia, T. R. Nagy, D. B. Allison and T. E. Johnson, “Strain Variation in the Response of Body Temperature to Dietary Restriction,” Mechanisms of Ageing and Development, Vol. 124, No. 5, 2003, pp. 663-678. doi:10.1016/S0047-6374(03)00003-4
[15] C. G. Tankersley, R. Irizarry, S. Flanders and R. Rabold, “Circadian Rhythm Variation in Activity, Body Temperature, and Heart Rate Between C3H/HeJ and C57BL/6J Inbred Strains,” Journal of Applied Physiology, Vol. 92, No. 2, 2002, pp. 870-877.
[16] E. Kilic, U. Kilic, M. Bacigaluppi, et al., “Delayed Melatonin Administration Promotes Neuronal Survival, Neurogenesis and Motor Recovery, and Attenuates Hyperactivity and Anxiety after Mild Focal Cerebral Ischemia in Mice,” Journal of Pineal Research, Vol. 45, No. 2, 2008, pp. 142-148. doi:10.1111/j.1600-079X.2008.00568.x
[17] B. Winter, G. Juckel, I. Viktorov, et al., “Anxious and Hyperactive Phenotype Following Brief Ischemic Episodes in Mice,” Biological Psychiatry, Vol. 57, No. 10, 2005, pp. 1166-1175. doi:10.1016/j.biopsych.2005.02.010
[18] U. Ebmeyer, G. Keilhoff, G. Wolf and W. R?se, “Strain Specific Differences in a Cardio-Pulmonary Resuscitation Rat Model,” Resuscitation, Vol. 53, No. 2, 2002, pp. 189-200. doi:10.1016/S0300-9572(02)00003-5
[19] F. Colbourne, H. Li, and A. M. Buchan, “Indefatigable CA1 Sector Neuroprotection with Mild Hypothermia Induced 6 Hours after Severe Forebrain Ischemia in Rats,” Journal of Cerebral Blood Flow and Metabolism, Vol. 19, No. 7, 1999, pp. 742-749. doi:10.1097/00004647-199907000-00003
[20] C. Coimbra, F. Boris-M?ller, M. Drake and T. Wieloch, “Diminished Neuronal Damage in the Rat Brain By Late Treatment with the Antipyretic Drug Dipyrone or Cooling Following Cerebral Ischemia,” Acta Neuropathologica, Vol. 92, No. 5, 1996, pp. 447-453. doi:10.1007/s004010050545
[21] D. L. Clark, M. DeButte-Smith and F. Colbourne, “Spontaneous Temperature Changes in the 2-Vessel Occlusion Model of Cerebral Ischemia in Rats,” Canadian Journal of Physiology Pharmacology, Vol. 85, No. 12, 2007, pp. 1263-1268. doi:10.1139/Y07-119
[22] S. J. Spencer, A. Mouihate and Q. J. Pittman, “Peripheral Inflammation Exacerbates Damage after Global Ischemia Independently of Temperature and Acute Brain Inflammation,” Stroke, Vol. 38, No. 5, 2007, pp. 1570-1577. doi:10.1161/STROKEAHA.106.476507
[23] D. W. Marion, Y. Leonov, M. Ginsberg, et al., “Resuscitative Hypothermia,” Critical Care Medicine, Vol. 24, No. 2, 1996, pp. S81-S89. doi:10.1097/00003246-199602000-00050
[24] W. D. Dietrich, R. Busto, I. Valdes and Y. Loor, “Effects of Normothermic Versus Mild Hyperthermic Forebrain Ischemia in Rats,” Stroke, Vol. 21, No. 9, 1990, pp. 1318-1325. doi:10.1161/01.STR.21.9.1318
[25] R. W. Hickey, P. M. Kochanek, H. Ferimer, H. L. Alexander, R. H. Garman and S. H. Graham, “Induced Hyperthermia Exacerbates Neurologic Neuronal Histologic Damage after Asphyxial Cardiac Arrest in Rats,” Critical Care Medicine, Vol. 31, No. 2, 2003, pp. 531-535. doi:10.1097/01.CCM.0000050323.84293.11
[26] O. Gavrilova, L. R. Leon, B. Marcus-Samuels, et al., “Torpor in Mice Is Induced by Both Leptindependent and Independent Mechanisms,” Proceedings of the National Academy of Science of the USA, * 7 December 1999, pp. 14623-14628. doi:10.1073/pnas.96.25.14623
[27] D. L. Clark, S. B. DeBow, M. D. Iseke and F. Colbourne, “Stress-Induced Fever after Postischemic Rectal Temperature Measurements in the Gerbil,” Canadian Journal of Physiology and Pharmacology, Vol. 81, No. 9, 2003, pp. 880-883. doi:10.1139/y03-083
[28] S. DeBow and F. Colbourne, “Brain Temperature Measurement and Regulation in Awake and Freely Moving Rodents,” Methods, Vol. 30, No. 2, 2003, pp. 167-171. doi:10.1016/S1046-2023(03)00080-X
[29] D. Corbett, S. Evans, C. Thomas, D. Wang and R. A. Jonas, “MK-801 Reduced Cerebral Ischemic Injury by Inducing Hypothermia,” Brain Research, Vol. 514, No. 2, 1990, pp. 300-304. doi:10.1016/0006-8993(90)91424-F
[30] S. Nurse and D. Corbett, “Neuroprotection after Several Days of Mild, Drug-Induced Hypothermia,” Journal of Cerebral Blood Flow and Metabolism, Vol. 16, No. 3, 1996, pp. 474-480. doi:10.1097/00004647-199605000-00014
[31] H. Zhu, B. P. Meloni, S. R. Moore, B. T. Majda and N. W. Knuckey, “Intravenous Administration of Magnesium Is Only Neuroprotective Following Transient Global Ischemia When Present with Post-Ischemic Mild Hypothermia,” Brain Research, Vol. 1014, No. 1-2, 2004, pp. 53- 60. doi:10.1016/j.brainres.2004.03.073
[32] F. Colbourne, G. R. Sutherland and R. N. Auer, “An Automated System for Regulating Brain Temperature in Awake and Freely Moving Rodents,” Journal of Neuro-science Methods, Vol. 67, No. 2, 1996, pp. 185-190. doi:10.1016/0165-0270(96)00047-7
[33] C. L. MacLellan, D. L. Clark, G. Silasi and F. Colbourne, “Use of Prolonged Hypothermia to Treat Ischemic and Hemorrhagic Stroke,” Journal of Neurotrauma, Vol. 26, No. 3, 2009, pp. 313-323. doi:10.1089/neu.2008.0580

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