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Molecular Mechanism of Reperfusion Injury

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Therapeutic Hypothermia After Cardiac Arrest

Abstract

In the 1950s, hypothermia was induced prior to surgery to assist procedures that caused prolonged ischemia, including heart surgery [1–3] and organ transplants [4]. Within its first decade, hypothermia was applied to emergent medical situations that were characterized by cerebral ischemia and stroke [5, 6] myocardial infarction (MI) [7, 8], and cardiac arrest patients [9, 10]_ENREF_10.

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References

  1. Lewis FJ. Hypothermia in cardiac and general surgery. Minn Med. 1955;38:77–81.

    PubMed  CAS  Google Scholar 

  2. Sealy WC, Brown Jr IW, Young Jr WG. A report on the use of both extracorporeal circulation and hypothermia for open heart surgery. Ann Surg. 1958;147:603–13.

    Article  PubMed  CAS  Google Scholar 

  3. Swan H. Hypothermia for general and cardiac surgery; with techniques of some open intracardiac procedures under hypothermia. Surg Clin North Am. 1956:1009–24.

    Google Scholar 

  4. Moossa AR, Zarins CK, Skinner DB. In situ kidney preservation for transplantation with use of profound hypothermia (5 to 20 degrees C.) with an intact circulation. Surgery. 1976;79:60–4.

    PubMed  CAS  Google Scholar 

  5. De Georgia MA, Krieger DW, Abou-Chebl A, et al. Cooling for Acute Ischemic Brain Damage (COOL AID): a feasibility trial of endovascular cooling. Neurology. 2004;63:312–7.

    Article  PubMed  Google Scholar 

  6. Hemmen TM, Raman R, Guluma KZ, et al. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke. 2010;41:2265–70.

    Article  PubMed  Google Scholar 

  7. Dae MW, Gao DW, Sessler DI, Chair K, Stillson CA. Effect of endovascular cooling on myocardial temperature, infarct size, and cardiac output in human-sized pigs. Am J Physiol Heart Circ Physiol. 2002;282:H1584–91.

    PubMed  CAS  Google Scholar 

  8. Miki T, Liu GS, Cohen MV, Downey JM. Mild hypothermia reduces infarct size in the beating rabbit heart: a practical intervention for acute myocardial infarction? Basic Res Cardiol. 1998;93:372–83.

    Article  PubMed  CAS  Google Scholar 

  9. Abella BS, Zhao D, Alvarado J, Hamann K, Vanden Hoek TL, Becker LB. Intra-arrest cooling improves outcomes in a murine cardiac arrest model. Circulation. 2004;109:2786–91.

    Article  PubMed  Google Scholar 

  10. Janata A, Holzer M. Hypothermia after cardiac arrest. Prog Cardiovasc Dis. 2009;52:168–79.

    Article  PubMed  Google Scholar 

  11. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–56.

    Article  Google Scholar 

  12. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557–63.

    Article  PubMed  Google Scholar 

  13. Tissier R, Hamanaka K, Kuno A, Parker JC, Cohen MV, Downey JM. Total liquid ventilation provides ultra-fast cardioprotective cooling. J Am Coll Cardiol. 2007;49:601–5.

    Article  PubMed  Google Scholar 

  14. Olivecrona GK, Gotberg M, Harnek J, Van der Pals J, Erlinge D. Mild hypothermia reduces cardiac post-ischemic reactive hyperemia. BMC Cardiovasc Disord. 2007;7:5.

    Article  PubMed  Google Scholar 

  15. Weisser J, Martin J, Bisping E, et al. Influence of mild hypothermia on myocardial contractility and circulatory function. Basic Res Cardiol. 2001;96:198–205.

    Article  PubMed  CAS  Google Scholar 

  16. Azmoon S, Demarest C, Pucillo AL, et al. Neurologic and cardiac benefits of therapeutic hypothermia. Cardiol Rev. 2011;19:108–14.

    Article  PubMed  Google Scholar 

  17. Heiss WD, Rosner G. Functional recovery of cortical neurons as related to degree and duration of ischemia. Ann Neurol. 1983;14:294–301.

    Article  PubMed  CAS  Google Scholar 

  18. Reimer KA, Jennings RB. The “wavefront phenomenon” of myocardial ischemic cell death. II. Transmural progression of necrosis within the framework of ­ischemic bed size (myocardium at risk) and collateral flow. Lab Invest. 1979;40:633–44.

    PubMed  CAS  Google Scholar 

  19. Braunwald E, Kloner RA. Myocardial reperfusion: a double-edged sword? J Clin Invest. 1985;76:1713–9.

    Article  PubMed  CAS  Google Scholar 

  20. Hallenbeck JM, Dutka AJ. Background review and current concepts of reperfusion injury. Arch Neurol. 1990;47:1245–54.

    Article  PubMed  CAS  Google Scholar 

  21. Ames 3rd A, Wright RL, Kowada M, Thurston JM, Majno G. Cerebral ischemia. II. The no-reflow phenomenon. Am J Pathol. 1968;52:437–53.

    PubMed  Google Scholar 

  22. Dietrich WD. Morphological manifestations of reperfusion injury in brain. Ann N Y Acad Sci. 1994;723:15–24.

    Article  PubMed  CAS  Google Scholar 

  23. Jennings RB, Sommers HM, Smyth GA, Flack HA, Linn H. Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Arch Pathol. 1960;70:68–78.

    PubMed  CAS  Google Scholar 

  24. Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007;357:1121–35.

    Article  PubMed  CAS  Google Scholar 

  25. Braunwald E, Kloner RA. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation. 1982;66:1146–9.

    Article  PubMed  CAS  Google Scholar 

  26. Krug A, Du Mesnil de Rochemont R, Korb G. Blood supply of the myocardium after temporary coronary occlusion. Circ Res. 1966;19:57–62.

    Article  PubMed  CAS  Google Scholar 

  27. Ito H. No-reflow phenomenon and prognosis in patients with acute myocardial infarction. Nat Clin Pract Cardiovasc Med. 2006;3:499–506.

    Article  PubMed  Google Scholar 

  28. Manning AS, Hearse DJ. Reperfusion-induced arrhythmias: mechanisms and prevention. J Mol Cell Cardiol. 1984;16:497–518.

    Article  PubMed  CAS  Google Scholar 

  29. Kloner RA. Does reperfusion injury exist in humans? J Am Coll Cardiol. 1993;21:537–45.

    Article  PubMed  CAS  Google Scholar 

  30. Piper HM, Garcia-Dorado D, Ovize M. A fresh look at reperfusion injury. Cardiovasc Res. 1998;38:291–300.

    Article  PubMed  CAS  Google Scholar 

  31. Yellon DM, Baxter GF. Reperfusion injury revisited: is there a role for growth factor signaling in limiting lethal reperfusion injury? Trends Cardiovasc Med. 1999;9:245–9.

    Article  PubMed  CAS  Google Scholar 

  32. Lampe JW, Becker LB. State of the art in therapeutic hypothermia. Annu Rev Med. 2011;62:79–93.

    Article  PubMed  CAS  Google Scholar 

  33. Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med. 2009;37:S186–202.

    Article  PubMed  Google Scholar 

  34. Badruddin A, Taqi MA, Abraham MG, Dani D, Zaidat OO. Neurocritical care of a reperfused brain. Curr Neurol Neurosci Rep. 2011;11:104–10.

    Article  PubMed  CAS  Google Scholar 

  35. Simon RP. Acidotoxicity trumps excitotoxicity in ischemic brain. Arch Neurol. 2006;63:1368–71.

    Article  PubMed  Google Scholar 

  36. Wahlgren NG, Ahmed N. Neuroprotection in cerebral ischaemia: facts and fancies – the need for new approaches. Cerebrovasc Dis. 2004;17 Suppl 1:153–66.

    Article  PubMed  CAS  Google Scholar 

  37. Leker RR, Shohami E. Cerebral ischemia and trauma-different etiologies yet similar mechanisms: neuroprotective opportunities. Brain Res Brain Res Rev. 2002;39:55–73.

    Article  PubMed  Google Scholar 

  38. Brennan AM, Suh SW, Won SJ, et al. NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation. Nat Neurosci. 2009;12:857–63.

    Article  PubMed  CAS  Google Scholar 

  39. Eldadah BA, Faden AI. Caspase pathways, neuronal apoptosis, and CNS injury. J Neurotrauma. 2000;17:811–29.

    Article  PubMed  CAS  Google Scholar 

  40. Tuttolomondo A, Di Sciacca R, Di Raimondo D, et al. Neuron protection as a therapeutic target in acute ischemic stroke. Curr Top Med Chem. 2009;9:1317–34.

    Article  PubMed  CAS  Google Scholar 

  41. Bolli R, Jeroudi MO, Patel BS, et al. Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion. Evidence that myocardial “stunning” is a manifestation of reperfusion injury. Circ Res. 1989;65:607–22.

    Article  PubMed  CAS  Google Scholar 

  42. Khalid MA, Ashraf M. Direct detection of endogenous hydroxyl radical production in cultured adult cardiomyocytes during anoxia and reoxygenation. Is the hydroxyl radical really the most damaging radical species? Circ Res. 1993;72:725–36.

    Article  PubMed  CAS  Google Scholar 

  43. Halliwell B. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet. 1994;344:721–4.

    Article  PubMed  CAS  Google Scholar 

  44. Sugawara T, Chan PH. Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia. Antioxid Redox Signal. 2003;5:597–607.

    Article  PubMed  CAS  Google Scholar 

  45. Wong CH, Crack PJ. Modulation of neuro-inflammation and vascular response by oxidative stress following cerebral ischemia-reperfusion injury. Curr Med Chem. 2008;15:1–14.

    Article  PubMed  CAS  Google Scholar 

  46. Huang Y, Rabb H, Womer KL. Ischemia-reperfusion and immediate T cell responses. Cell Immunol. 2007;248:4–11.

    Article  PubMed  CAS  Google Scholar 

  47. Jung JE, Kim GS, Chen H, et al. Reperfusion and neurovascular dysfunction in stroke: from basic mechanisms to potential strategies for neuroprotection. Mol Neurobiol. 2010;41:172–9.

    Article  PubMed  CAS  Google Scholar 

  48. Lu XC, Hartings JA, Si Y, Balbir A, Cao Y, Tortella FC. Electrocortical pathology in a rat model of penetrating ballistic-like brain injury. J Neurotrauma. 2011;28:71–83.

    Article  PubMed  Google Scholar 

  49. Bernard SA, Buist M. Induced hypothermia in critical care medicine: a review. Crit Care Med. 2003;31:2041–51.

    Article  PubMed  Google Scholar 

  50. Howes D, Green R, Gray S, Stenstrom R, Easton D. Evidence for the use of hypothermia after cardiac arrest. CJEM. 2006;8:109–15.

    PubMed  Google Scholar 

  51. Shao ZH, Sharp WW, Wojcik KR, et al. Therapeutic hypothermia cardioprotection via Akt- and nitric oxide-mediated attenuation of mitochondrial oxidants. Am J Physiol Heart Circ Physiol. 2010;298:H2164–73.

    Article  PubMed  CAS  Google Scholar 

  52. Yang D, Guo S, Zhang T, Li H. Hypothermia attenuates ischemia/reperfusion-induced endothelial cell apoptosis via alterations in apoptotic pathways and JNK signaling. FEBS Lett. 2009;583:2500–6.

    Article  PubMed  CAS  Google Scholar 

  53. Erecinska M, Thoresen M, Silver IA. Effects of hypothermia on energy metabolism in Mammalian central nervous system. J Cereb Blood Flow Metab. 2003;23:513–30.

    Article  PubMed  CAS  Google Scholar 

  54. Gadzinski DS, White BC, Hoehner PJ, Hoehner T, Krome C, White JD. Canine cerebral cortical blood flow and vascular resistance post cardiac arrest. Ann Emerg Med. 1982;11:58–63.

    Article  PubMed  CAS  Google Scholar 

  55. Snyder JV, Nemoto EM, Carroll RG, Safar P. Global ischemia in dogs: intracranial pressures, brain blood flow and metabolism. Stroke. 1975;6:21–7.

    Article  PubMed  CAS  Google Scholar 

  56. Drewes LR, Gilboe DD, Betz AL. Metabolic alterations in brain during anoxic-anoxia and subsequent recovery. Arch Neurol. 1973;29:385–90.

    Article  PubMed  CAS  Google Scholar 

  57. Kowada M, Ames 3rd A, Majno G, Wright RL. Cerebral ischemia. I. An improved experimental method for study; cardiovascular effects and demonstration of an early vascular lesion in the rabbit. J Neurosurg. 1968;28:150–7.

    Article  PubMed  CAS  Google Scholar 

  58. Van Nueten JM, Vanhoutte PM. Improvement of tissue perfusion with inhibitors of calcium ion influx. Biochem Pharmacol. 1980;29:479–81.

    Article  PubMed  Google Scholar 

  59. Shen AC, Jennings RB. Myocardial calcium and magnesium in acute ischemic injury. Am J Pathol. 1972;67:417–40.

    PubMed  CAS  Google Scholar 

  60. Cavero I, Boudot JP, Feuvray D. Diltiazem protects the isolated rabbit heart from the mechanical and ultrastructural damage produced by transient hypoxia, low-flow ischemia and exposure to Ca++-free medium. J Pharmacol Exp Ther. 1983;226:258–68.

    PubMed  CAS  Google Scholar 

  61. Nayler WG, Ferrari R, Williams A. Protective effect of pretreatment with verapamil, nifedipine and propranolol on mitochondrial function in the ischemic and reperfused myocardium. Am J Cardiol. 1980;46:242–8.

    Article  PubMed  CAS  Google Scholar 

  62. Nayler WG, Panagiotopoulos S, Elz JS, Daly MJ. Calcium-mediated damage during post-ischaemic reperfusion. J Mol Cell Cardiol. 1988;20 Suppl 2:41–54.

    Article  PubMed  CAS  Google Scholar 

  63. Talukder MA, Zweier JL, Periasamy M. Targeting calcium transport in ischaemic heart disease. Cardiovasc Res. 2009;84:345–52.

    Article  PubMed  CAS  Google Scholar 

  64. Dirksen MT, Laarman GJ, Simoons ML, Duncker DJ. Reperfusion injury in humans: a review of clinical trials on reperfusion injury inhibitory strategies. Cardiovasc Res. 2007;74:343–55.

    Article  PubMed  CAS  Google Scholar 

  65. Bush LR, Romson JL, Ash JL, Lucchesi BR. Effect of diltiazem on extent of ultimate myocardial injury resulting from temporary coronary artery occlusion in dogs. J Cardiovasc Pharmacol. 1982;4:285–96.

    Article  PubMed  CAS  Google Scholar 

  66. Standefer M, Little JR. Improved neurological outcome in experimental focal cerebral ischemia treated with propranolol. Neurosurgery. 1986;18:136–40.

    Article  PubMed  CAS  Google Scholar 

  67. Lamping KA, Gross GJ. Improved recovery of myocardial segment function following a short coronary occlusion in dogs by nicorandil, a potential new antianginal agent, and nifedipine. J Cardiovasc Pharmacol. 1985;7:158–66.

    Article  PubMed  CAS  Google Scholar 

  68. Przyklenk K, Ghafari GB, Eitzman DT, Kloner RA. Nifedipine administered after reperfusion ablates ­systolic contractile dysfunction of postischemic “stunned” myocardium. J Am Coll Cardiol. 1989;13:1176–83.

    Article  PubMed  CAS  Google Scholar 

  69. Gross GJ, Farber NE, Pieper GM. Effects of ­amlodipine on myocardial ischemia-reperfusion injury in dogs. Am J Cardiol. 1989;64:94I–100.

    Article  PubMed  CAS  Google Scholar 

  70. Blaustein MP, Lederer WJ. Sodium/calcium exchange: its physiological implications. Physiol Rev. 1999;79:763–854.

    PubMed  CAS  Google Scholar 

  71. Ohtsuka M, Takano H, Suzuki M, et al. Role of Na+-Ca2+ exchanger in myocardial ischemia/reperfusion injury: evaluation using a heterozygous Na+-Ca2+ exchanger knockout mouse model. Biochem Biophys Res Commun. 2004;314:849–53.

    Article  PubMed  CAS  Google Scholar 

  72. Inserte J, Garcia-Dorado D, Ruiz-Meana M, et al. Effect of inhibition of Na(+)/Ca(2+) exchanger at the time of myocardial reperfusion on hypercontracture and cell death. Cardiovasc Res. 2002;55:739–48.

    Article  PubMed  CAS  Google Scholar 

  73. Vittone L, Mundina-Weilenmann C, Mattiazzi A. Phospholamban phosphorylation by CaMKII under pathophysiological conditions. Front Biosci. 2008;13:5988–6005.

    Article  PubMed  CAS  Google Scholar 

  74. Karmazyn M. Pharmacology and clinical assessment of cariporide for the treatment coronary artery diseases. Expert Opin Investig Drugs. 2000;9:1099–108.

    Article  PubMed  CAS  Google Scholar 

  75. Avkiran M, Marber MS. Na(+)/H(+) exchange inhibitors for cardioprotective therapy: progress, problems and prospects. J Am Coll Cardiol. 2002;39:747–53.

    Article  PubMed  CAS  Google Scholar 

  76. Murphy E, Allen DG. Why did the NHE inhibitor clinical trials fail? J Mol Cell Cardiol. 2009;46:137–41.

    Article  PubMed  CAS  Google Scholar 

  77. Shi Y, Chanana V, Watters JJ, Ferrazzano P, Sun D. Role of sodium/hydrogen exchanger isoform 1 in microglial activation and proinflammatory respon­ses in ischemic brains. J Neurochem. 2011;119:124–35.

    Article  PubMed  CAS  Google Scholar 

  78. Barry WH, Zhang XQ, Halkos ME, et al. Nonanticoagulant heparin reduces myocyte Na+ and Ca2+ loading during simulated ischemia and decreases reperfusion injury. Am J Physiol Heart Circ Physiol. 2010;298:H102–11.

    Article  PubMed  CAS  Google Scholar 

  79. Opie LH. Reperfusion injury and its pharmacologic modification. Circulation. 1989;80:1049–62.

    Article  PubMed  CAS  Google Scholar 

  80. Myers CL, Weiss SJ, Kirsh MM, Shlafer M. Involvement of hydrogen peroxide and hydroxyl radical in the ‘oxygen paradox’: reduction of creatine kinase release by catalase, allopurinol or deferoxamine, but not by superoxide dismutase. J Mol Cell Cardiol. 1985;17:675–84.

    Article  PubMed  CAS  Google Scholar 

  81. Ambrosio G, Weisfeldt ML, Jacobus WE, Flaherty JT. Evidence for a reversible oxygen radical-mediated component of reperfusion injury: reduction by recombinant human superoxide dismutase administered at the time of reflow. Circulation. 1987;75:282–91.

    Article  PubMed  CAS  Google Scholar 

  82. Bolli R, Patel BS, Jeroudi MO, Lai EK, McCay PB. Demonstration of free radical generation in “stunned” myocardium of intact dogs with the use of the spin trap alpha-phenyl N-tert-butyl nitrone. J Clin Invest. 1988;82:476–85.

    Article  PubMed  CAS  Google Scholar 

  83. Bolli R, Zhu WX, Hartley CJ, et al. Attenuation of ­dysfunction in the postischemic ‘stunned’ myocardium by dimethylthiourea. Circulation. 1987;76:458–68.

    Article  PubMed  CAS  Google Scholar 

  84. Grieb P, Ryba MS, Debicki GS, Gordon-Krajcer W, Januszewski S, Chrapusta SJ. Changes in oxidative stress in the rat brain during post-cardiac arrest reperfusion, and the effect of treatment with the free radical scavenger idebenone. Resuscitation. 1998;39:107–13.

    Article  PubMed  CAS  Google Scholar 

  85. Taniguchi M, Uchinami M, Doi K, et al. Edaravone reduces ischemia-reperfusion injury mediators in rat liver. J Surg Res. 2007;137:69–74.

    Article  PubMed  CAS  Google Scholar 

  86. Watanabe T, Tahara M, Todo S. The novel antioxidant edaravone: from bench to bedside. Cardiovasc Ther. 2008;26:101–14.

    Article  PubMed  CAS  Google Scholar 

  87. Amaro S, Chamorro A. Translational stroke research of the combination of thrombolysis and antioxidant therapy. Stroke. 2011;42:1495–9.

    Article  PubMed  CAS  Google Scholar 

  88. Jain KK. Neuroprotection in cerebrovascular disease. Expert Opin Investig Drugs. 2000;9:695–711.

    Article  PubMed  CAS  Google Scholar 

  89. Zhang YE, Fu SZ, Li XQ, et al. PEP-1-SOD1 protects brain from ischemic insult following asphyxial cardiac arrest in rats. Resuscitation. 2011;82:1081–6.

    Article  PubMed  CAS  Google Scholar 

  90. Yamazaki K, Miwa S, Toyokuni S, et al. Effect of edaravone, a novel free radical scavenger, supplemented to cardioplegia on myocardial function after cardioplegic arrest: in vitro study of isolated rat heart. Heart Vessels. 2009;24:228–35.

    Article  PubMed  Google Scholar 

  91. Wiklund L, Sharma HS, Basu S. Circulatory arrest as a model for studies of global ischemic injury and neuroprotection. Ann N Y Acad Sci. 2005;1053:205–19.

    Article  PubMed  Google Scholar 

  92. Tang XN, Liu L, Yenari MA. Combination therapy with hypothermia for treatment of cerebral ischemia. J Neurotrauma. 2009;26:325–31.

    Article  PubMed  Google Scholar 

  93. Meybohm P, Gruenewald M, Albrecht M, et al. Hypothermia and postconditioning after cardiopulmonary resuscitation reduce cardiac dysfunction by modulating inflammation, apoptosis and remodeling. PLoS One. 2009;4:e7588.

    Article  PubMed  CAS  Google Scholar 

  94. Schwiebert C, Huhn R, Heinen A, et al. Postconditioning by xenon and hypothermia in the rat heart in vivo. Eur J Anaesthesiol. 2010;27:734–9.

    PubMed  CAS  Google Scholar 

  95. Schmid-Elsaesser R, Hungerhuber E, Zausinger S, Baethmann A, Reulen HJ. Combination drug therapy and mild hypothermia: a promising treatment strategy for reversible, focal cerebral ischemia. Stroke. 1999;30:1891–9.

    Article  PubMed  CAS  Google Scholar 

  96. Zausinger S, Scholler K, Plesnila N, Schmid-Elsaesser R. Combination drug therapy and mild hypothermia after transient focal cerebral ischemia in rats. Stroke. 2003;34:2246–51.

    Article  PubMed  CAS  Google Scholar 

  97. Scholler K, Zausinger S, Baethmann A, Schmid-Elsaesser R. Neuroprotection in ischemic stroke – combination drug therapy and mild hypothermia in a rat model of permanent focal cerebral ischemia. Brain Res. 2004;1023:272–8.

    Article  PubMed  CAS  Google Scholar 

  98. Aronowski J, Strong R, Shirzadi A, Grotta JC. Ethanol plus caffeine (caffeinol) for treatment of ischemic stroke: preclinical experience. Stroke. 2003;34:1246–51.

    Article  PubMed  CAS  Google Scholar 

  99. Martin-Schild S, Hallevi H, Shaltoni H, et al. Combined neuroprotective modalities coupled with thrombolysis in acute ischemic stroke: a pilot study of caffeinol and mild hypothermia. J Stroke Cerebrovasc Dis. 2009;18:86–96.

    Article  PubMed  Google Scholar 

  100. Nito C, Kamiya T, Ueda M, Arii T, Katayama Y. Mild hypothermia enhances the neuroprotective effects of FK506 and expands its therapeutic window following transient focal ischemia in rats. Brain Res. 2004;1008:179–85.

    Article  PubMed  CAS  Google Scholar 

  101. Dietrich WD, Busto R, Alonso O, Globus MY, Ginsberg MD. Intraischemic but not postischemic brain hypothermia protects chronically following global forebrain ischemia in rats. J Cereb Blood Flow Metab. 1993;13:541–9.

    Article  PubMed  CAS  Google Scholar 

  102. Green EJ, Dietrich WD, van Dijk F, et al. Protective effects of brain hypothermia on behavior and histopathology following global cerebral ischemia in rats. Brain Res. 1992;580:197–204.

    Article  PubMed  CAS  Google Scholar 

  103. Dietrich WD, Busto R, Bethea JR. Postischemic hypothermia and IL-10 treatment provide long-lasting neuroprotection of CA1 hippocampus following transient global ischemia in rats. Exp Neurol. 1999;158:444–50.

    Article  PubMed  CAS  Google Scholar 

  104. Meybohm P, Gruenewald M, Zacharowski KD, et al. Mild hypothermia alone or in combination with anesthetic post-conditioning reduces expression of inflammatory cytokines in the cerebral cortex of pigs after cardiopulmonary resuscitation. Crit Care. 2010;14:R21.

    Article  PubMed  Google Scholar 

  105. Holzer M. Targeted temperature management for comatose survivors of cardiac arrest. N Engl J Med. 2010;363:1256–64.

    Article  PubMed  CAS  Google Scholar 

  106. Holzer M, Bernard SA, Hachimi-Idrissi S, Roine RO, Sterz F, Mullner M. Hypothermia for neuroprotection after cardiac arrest: systematic review and individual patient data meta-analysis. Crit Care Med. 2005;33:414–8.

    Article  PubMed  Google Scholar 

  107. Abendschein DR, Tacker Jr WA, Babbs CF. Protection of ischemic myocardium by whole-body hypothermia after coronary artery occlusion in dogs. Am Heart J. 1978;96:772–80.

    Article  PubMed  CAS  Google Scholar 

  108. Ly HQ, Denault A, Dupuis J, et al. A pilot study: the Noninvasive Surface Cooling Thermoregulatory System for Mild Hypothermia Induction in Acute Myocardial Infarction (the NICAMI Study). Am Heart J. 2005;150:933.

    Article  PubMed  Google Scholar 

  109. Kandzari DE, Chu A, Brodie BR, et al. Feasibility of endovascular cooling as an adjunct to primary percutaneous coronary intervention (results of the LOWTEMP pilot study). Am J Cardiol. 2004;93:636–9.

    Article  PubMed  Google Scholar 

  110. Stone GW, Dixon SR, Grines CL, et al. Predictors of infarct size after primary coronary angioplasty in acute myocardial infarction from pooled analysis from four contemporary trials. Am J Cardiol. 2007;100:1370–5.

    Article  PubMed  Google Scholar 

  111. O’Neill WW, Dixon SR, Grines CL. The year in interventional cardiology. J Am Coll Cardiol. 2005;45:1117–34.

    Article  PubMed  Google Scholar 

  112. Tissier R, Chenoune M, Ghaleh B, Cohen MV, Downey JM, Berdeaux A. The small chill: mild hypothermia for cardioprotection? Cardiovasc Res. 2010;88:406–14.

    Article  PubMed  CAS  Google Scholar 

  113. Busl KM, Greer DM. Hypoxic-ischemic brain injury: pathophysiology, neuropathology and mechanisms. NeuroRehabilitation. 2010;26:5–13.

    PubMed  Google Scholar 

  114. Greer DM. Mechanisms of injury in hypoxic-ischemic encephalopathy: implications to therapy. Semin Neurol. 2006;26:373–9.

    Article  PubMed  Google Scholar 

  115. Hoesch RE, Koenig MA, Geocadin RG. Coma after global ischemic brain injury: pathophysiology and emerging therapies. Crit Care Clin. 2008;24:25–44. vii–viii.

    Article  PubMed  Google Scholar 

  116. Redmond JM, Gillinov AM, Zehr KJ, et al. Glutamate excitotoxicity: a mechanism of neurologic injury associated with hypothermic circulatory arrest. J Thorac Cardiovasc Surg. 1994;107:776–86. discussion 86–7.

    PubMed  CAS  Google Scholar 

  117. Szydlowska K, Tymianski M. Calcium, ischemia and excitotoxicity. Cell Calcium. 2010;47:122–9.

    Article  PubMed  CAS  Google Scholar 

  118. Bokesch PM, Halpin DP, Ranger WR, et al. Immediate-early gene expression in ovine brain after hypothermic circulatory arrest: effects of aptiganel. Ann Thorac Surg. 1997;64:1082–7. discussion 8.

    Article  PubMed  CAS  Google Scholar 

  119. Nolan JP, Neumar RW, Adrie C, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke. Resuscitation. 2008;79:350–79.

    Article  PubMed  Google Scholar 

  120. Sterz F, Leonov Y, Safar P, et al. Multifocal cerebral blood flow by Xe-CT and global cerebral metabolism after prolonged cardiac arrest in dogs. Reperfusion with open-chest CPR or cardiopulmonary bypass. Resuscitation. 1992;24:27–47.

    Article  PubMed  CAS  Google Scholar 

  121. Ernster L. Biochemistry of reoxygenation injury. Crit Care Med. 1988;16:947–53.

    Article  PubMed  CAS  Google Scholar 

  122. McCullough JN, Zhang N, Reich DL, et al. Cerebral metabolic suppression during hypothermic circulatory arrest in humans. Ann Thorac Surg. 1999;67:1895–9. discussion 919–21.

    Article  PubMed  CAS  Google Scholar 

  123. D’Cruz BJ, Fertig KC, Filiano AJ, Hicks SD, DeFranco DB, Callaway CW. Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation. J Cereb Blood Flow Metab. 2002;22:843–51.

    Article  PubMed  Google Scholar 

  124. Hachimi-Idrissi S, Van Hemelrijck A, Michotte A, et al. Postischemic mild hypothermia reduces neurotransmitter release and astroglial cell proliferation during reperfusion after asphyxial cardiac arrest in rats. Brain Res. 2004;1019:217–25.

    Article  PubMed  CAS  Google Scholar 

  125. Maier CM, Sun GH, Cheng D, Yenari MA, Chan PH, Steinberg GK. Effects of mild hypothermia on superoxide anion production, superoxide dismutase expression, and activity following transient focal cerebral ischemia. Neurobiol Dis. 2002;11:28–42.

    Article  PubMed  CAS  Google Scholar 

  126. Lei B, Tan X, Cai H, Xu Q, Guo Q. Effect of ­moderate hypothermia on lipid peroxidation in canine brain tissue after cardiac arrest and resuscitation. Stroke. 1994;25:147–52.

    Article  PubMed  CAS  Google Scholar 

  127. Eberspacher E, Werner C, Engelhard K, et al. Long-term effects of hypothermia on neuronal cell death and the concentration of apoptotic proteins after incomplete cerebral ischemia and reperfusion in rats. Acta Anaesthesiol Scand. 2005;49:477–87.

    Article  PubMed  CAS  Google Scholar 

  128. Webster CM, Kelly S, Koike MA, Chock VY, Giffard RG, Yenari MA. Inflammation and NFkappaB ­activation is decreased by hypothermia following global cerebral ischemia. Neurobiol Dis. 2009;33:301–12.

    Article  PubMed  CAS  Google Scholar 

  129. Karibe H, Zarow GJ, Graham SH, Weinstein PR. Mild intraischemic hypothermia reduces postischemic hyperperfusion, delayed postischemic hypoperfusion, blood–brain barrier disruption, brain edema, and neuronal damage volume after temporary focal cerebral ischemia in rats. J Cereb Blood Flow Metab. 1994;14:620–7.

    Article  PubMed  CAS  Google Scholar 

  130. Sakurai A. Therapeutic hypothermia. Nihon Rinsho. 2011;69:642–7.

    PubMed  Google Scholar 

  131. Hoehn T, Hansmann G, Buhrer C, et al. Therapeutic hypothermia in neonates. Review of current clinical data, ILCOR recommendations and suggestions for implementation in neonatal intensive care units. Resuscitation. 2008;78:7–12.

    Article  PubMed  Google Scholar 

  132. Wolfrum S, Radke PW, Pischon T, Willich SN, Schunkert H, Kurowski V. Mild therapeutic hypothermia after cardiac arrest – a nationwide survey on the implementation of the ILCOR guidelines in German intensive care units. Resuscitation. 2007;72:207–13.

    Article  PubMed  Google Scholar 

  133. van der Worp HB, Sena ES, Donnan GA, Howells DW, Macleod MR. Hypothermia in animal models of acute ischaemic stroke: a systematic review and meta-analysis. Brain. 2007;130:3063–74.

    Article  PubMed  Google Scholar 

  134. Den Hertog HM, van der Worp HB, Tseng MC, Dippel DW. Cooling therapy for acute stroke. Cochrane Database Syst Rev. 2009: CD001247.

    Google Scholar 

  135. Hemmen TM, Lyden PD. Induced hypothermia for acute stroke. Stroke. 2007;38:794–9.

    Article  PubMed  Google Scholar 

  136. Dietrich WD, Alonso O, Busto R, et al. Posttraumatic cerebral ischemia after fluid percussion brain injury: an autoradiographic and histopathological study in rats. Neurosurgery. 1998;43:585–93. discussion 93–4.

    Article  PubMed  CAS  Google Scholar 

  137. Chesnut RM, Marshall SB, Piek J, Blunt BA, Klauber MR, Marshall LF. Early and late systemic hypotension as a frequent and fundamental source of cerebral ischemia following severe brain injury in the Traumatic Coma Data Bank. Acta Neurochir Suppl (Wien). 1993;59:121–5.

    CAS  Google Scholar 

  138. Matsushita Y, Bramlett HM, Alonso O, Dietrich WD. Posttraumatic hypothermia is neuroprotective in a model of traumatic brain injury complicated by a secondary hypoxic insult. Crit Care Med. 2001;29:2060–6.

    Article  PubMed  CAS  Google Scholar 

  139. Muizelaar JP. Cerebral ischemia-reperfusion injury after severe head injury and its possible treatment with polyethyleneglycol-superoxide dismutase. Ann Emerg Med. 1993;22:1014–21.

    Article  PubMed  CAS  Google Scholar 

  140. Miller JD, Bullock R, Graham DI, Chen MH, Teasdale GM. Ischemic brain damage in a model of acute subdural hematoma. Neurosurgery. 1990;27:433–9.

    Article  PubMed  CAS  Google Scholar 

  141. Kuroda Y, Bullock R. Local cerebral blood flow mapping before and after removal of acute subdural hematoma in the rat. Neurosurgery. 1992;30:687–91.

    Article  PubMed  CAS  Google Scholar 

  142. Burger R, Bendszus M, Vince GH, Solymosi L, Roosen K. Neurophysiological monitoring, magnetic resonance imaging, and histological assays confirm the beneficial effects of moderate hypothermia after epidural focal mass lesion development in rodents. Neurosurgery. 2004;54:701–11. discussion 11–2.

    Article  PubMed  Google Scholar 

  143. Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med. 2001;344:556–63.

    Article  PubMed  CAS  Google Scholar 

  144. Clifton GL, Valadka A, Zygun D, et al. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol. 2011;10:131–9.

    Article  PubMed  Google Scholar 

  145. Farkas O, Povlishock JT. Cellular and subcellular change evoked by diffuse traumatic brain injury: a complex web of change extending far beyond focal damage. Prog Brain Res. 2007;161:43–59.

    Article  PubMed  CAS  Google Scholar 

  146. Jieyong B, Zhong W, Shiming Z, et al. Decompressive craniectomy and mild hypothermia reduces infarction size and counterregulates Bax and Bcl-2 expression after permanent focal ischemia in rats. Neurosurg Rev. 2006;29:168–72.

    Article  PubMed  Google Scholar 

  147. Liu MC, Akinyi L, Scharf D, et al. Ubiquitin C-terminal hydrolase-L1 as a biomarker for ischemic and traumatic brain injury in rats. Eur J Neurosci. 2010;31:722–32.

    Article  PubMed  Google Scholar 

  148. Papa L, Akinyi L, Liu MC, et al. Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury. Crit Care Med. 2010;38:138–44.

    Article  PubMed  CAS  Google Scholar 

  149. Okauchi M, Kawai N, Nakamura T, Kawanishi M, Nagao S. Effects of mild hypothermia and alkalizing agents on brain injuries in rats with acute subdural hematomas. J Neurotrauma. 2002;19:741–51.

    Article  PubMed  Google Scholar 

  150. Bederson JB, Pitts LH, Germano SM, Nishimura MC, Davis RL, Bartkowski HM. Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. Stroke. 1986;17:1304–8.

    Article  PubMed  CAS  Google Scholar 

  151. Colbourne F, Corbett D. Delayed and prolonged post-ischemic hypothermia is neuroprotective in the gerbil. Brain Res. 1994;654:265–72.

    Article  PubMed  CAS  Google Scholar 

  152. Logue ES, McMichael MJ, Callaway CW. Comparison of the effects of hypothermia at 33 degrees C or 35 degrees C after cardiac arrest in rats. Acad Emerg Med. 2007;14:293–300.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, Japan

    Shoji Yokobori M.D., Ph.D.

  2. Department of Neurosurgery, Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA

    Shoji Yokobori M.D., Ph.D., M. Ross Bullock M.D., Ph.D. & W. Dalton Dietrich Ph.D.

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  1. Shoji Yokobori M.D., Ph.D.
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  2. M. Ross Bullock M.D., Ph.D.
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  3. W. Dalton Dietrich Ph.D.
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Correspondence to W. Dalton Dietrich Ph.D. .

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  1. , School of Medicine, University of Connecticut, Hartford, 06102-5037, Connecticut, USA

    Justin B. Lundbye

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Yokobori, S., Bullock, M.R., Dietrich, W.D. (2012). Molecular Mechanism of Reperfusion Injury. In: Lundbye, J. (eds) Therapeutic Hypothermia After Cardiac Arrest. Springer, London. https://doi.org/10.1007/978-1-4471-2951-6_3

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