Abstract
Despite more than 80 years of animal experiments and clinical practice, efficacy of hypothermia in improving treatment outcomes in patients suffering from cell and tissue damage caused by ischemia is still ongoing. This review will first describe the history of utilizing cooling in medical treatment, followed by chemical and biochemical mechanisms of cooling that can lead to neuroprotection often observed in animal studies and some clinical studies. The next sections will be focused on current cooling approaches/devices, as well as cooling parameters recommended by researchers and clinicians. Animal and clinical studies of implementing hypothermia to spinal cord and brain tissue injury patients are presented next. This section will review the latest outcomes of hypothermia in treating patients suffering from traumatic brain injury (TBI), spinal cord injury (SCI), stroke, cardiopulmonary surgery, and cardiac arrest, followed by a summary of available evidence regarding both demonstrated neuroprotection and potential risks of hypothermia. Contributions from bioengineers to the field of hypothermia in medical treatment will be discussed in the last section of this review. Overall, an accumulating body of clinical evidence along with several decades of animal research and mathematical simulations has documented that the efficacy of hypothermia is dependent on achieving a reduced temperature in the target tissue before or soon after the injury-precipitating event. Mild hypothermia with temperature reduction of several degrees Celsius is as effective as modest or deep hypothermia in providing therapeutic benefit without introducing collateral/systemic complications. It is widely demonstrated that the rewarming rate must be controlled to be lower than 0.5 °C/h to avoid mismatch between local blood perfusion and metabolism. In the past several decades, many different cooling methods and devices have been designed, tested, and used in medical treatments with mixed results. Accurately designing treatment protocols to achieve specific cooling outcomes requires collaboration among engineers, researchers, and clinicians. Although this problem is quite challenging, it presents a major opportunity for bioengineers to create methods and devices that quickly and safely produce hypothermia in targeted tissue regions without interfering with routine medical treatment.
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References
Abou-Chebl A, Sung G, Barbut D, Torbey M (2011) Local brain temperature reduction through intrnasal cooling with the RhinoChill device: preliminary safety data in brain-injured patients. Stroke 42:2164–2169
Andrews PJ, Harris B, Murray GD (2005) Randomized controlled trial of effects of the airflow through the upper respiratory tract of intubated brain-injured patients on brain temperature and selective brain cooling. Br J Anaesth 94:330–335
Andrews PJ, Sinclair HL, Rodriguez A, Harris BA, Battison CG, Rhodes JK et al (2015) Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med 373:2403–2412
Bachet J, Guilmet D (2002) Brain protection during surgery of the aortic arch. J Card Surg 17(2):115–124
Barone FC, Feuerstein GZ, White RF (1997) Brain cooling during transient focal ischemia provides complete neuroprotection. Neurosci Biobehav Rev 21:31–44
Batchelor PE, Kerr NF, Gatt AM, Aleksoska E, Cox SF, Ghasem-Zadeh A, Wills TE, Howells DW (2010) Hypothermia prior to decompression: buying time for treatment of acute spinal cord injury. J Neurotrauma 27:1357–1368
Belliard G, Catez E, Charron C et al (2007) Efficacy of therapeutic hypothermia after out-of-hospital cardiac arrest due to ventricular fibrillation. Resuscitation 75:252–259
Bernard SA, Gray TW, Buist MD, Jones BM, Silverster W et al (2002) Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346:557–563
Bernard S, Rosalion A (2008) Therapeutic hypothermia induced during cardiopulmonary resuscitation using large-volume, ice-cold intravenous fluid. Resuscitation 76:311–313
Bering E (1961) Effect of body temperature change on cerebral oxygen consumption of the intact monkey. Am J Phys 200:417–419
Berrouschot J, Sterker M, Bettin S, Koster J, Schneider D (1998) Mortality of space-occupying (“malignant”) middle cerebral artery infarction under conservative intensive care. Intensive Care Med 24:620–623
Bigelow WG, Callaghan JC, Hopps VA (1950) General hypothermia for experimental intracardiac surgery: use of artificial pacemaker for cardiac standstill and cardiac rewarming in general hypothermia. Ann Surg 132:531–543
Bohn DJ, Biggar WD, Smith CR, Conn AW, Baker GA (1986) Influence of hypothermia, barbiturate therapy, and intracranial pressure monitoring on morbidity and mortality after near-drowning. Crit Care Med 14:529–534
Bommadevera M, Zhu L (2002) Temperature difference between the body core and the arterial blood supplied to the brain during hyperthermia or hypothermia in humans. Biomech Model Mechanobiol 1(2):137–149
Bricolo A, Ore GD, da Pian R, Faccioli F (1976) Local cooling in spinal cord injury. Surg Neurol 6:101–106
Busija DW, Leffler CW (1987) Hypothermia reduces cerebral metabolic rate and cerebral blood flow in newborn pigs. Am J Phys 253:H869–H873
Busto R, Dietrich WD, Globus MY-T, Valdes I, Scheinberg P, Ginsberg MD (1987) Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab 7:729–738
Cappuccino A, Bisson LJ, Carpenter B, Marzo J, Dietrich WD, Cappuccino H (2010) The use of systemic hypothermia for the treatment of an acute cervical spinal cord injury in a professional football player. Spine 35:E57–E62
Chambers S (1999) Induced hypothermia for head injury. Nurs Crit Care 4:112–116
Carney N, Totten AM, O’Reilley C, Ullman JS, Havryluk GW Bell MJ et al (2017) Guidelines for the management of severe traumatic brain injury, 4th edition. Neurosurgery 80(1):6–15
Cheriyan T, Yoshihara H, Maier SP II, Ryan DJ, Weinreb JH, Errico TJ (2014) Neuroprotective effect of prophylactic intrathecal methylprednisolone in spinal cord injury in rat model. Spine J 14(11):S86–S87
Choi JH, Bateman BT, Mangla S, Marshall RS, Probhakaran S, Chong J et al (2006) Endovascular recanalization therapy in acute ischemic stroke. Stroke 37:419–424
Choi JH, Marshall RS, Neimark MA, Konstas AA, Lin E, Chiang YT et al (2010) Selective brain cooling with endovascular intracarotid infusion of cold saline: a pilot feasibility study. Am J Neuroradiol 31:928–934
Clifton GL, Allen S, Barrodale P, Plenger P, Berry J et al (1993) A phase II study of moderate hypothermia in severe brain injury. J Neurotrauma 10:263–271
Clifton GL, Miller ER, Choi SC, Levin HS, McCauley S et al (2001) Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 344:556–563
Clifton GL, Miller ER, Choi SC, Levin HS, McCauley S et al (2002) Hypothermia on admission in patients with severe brain injury. J Neurotrauma 19:293–301
Clifton GL, Valadka A, al ZD (2011) Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: hypothermia II): a randomised trial. Lancet Neurol 10(2):131–139
Colbourne F, Corbett D (1995) Delayed postischemic hypothermia: a six month survival study using behavioral and histological assessments of neuroprotection. J Neurosci 15:7250–7260
Covaciu L, Weis J, Bengtsson C, Allers M, Lunderquist A, Ahistrom H et al (2011) Brain temperature in volunteers subjected to intranasal cooling. Intensive Care Med 37:1277–1284
Dae MW, Gao DW, Ursell PC, Stillson CA, Sessler DI (2003) Safety and efficacy of endovascular cooling and rewarming for induction and reversal of hypothermia in human-sized pigs. Stroke 34:734–738
de Georgia MA, Krieger DW, Abou-Chebl A, Devlin TG, Jauss M et al (2004) Cooling for acute ischemic brain damage (COOL AID) a feasibility trial of endovascular cooling. Neurology 63:312–317
Dennis BH, Eberhart RC, Dulikravich GS, Radons SW (2003) Finite element simulation of cooling of realistic 3-D human head and neck. J Biomech Eng 125:832–840
Dididze M, Green BA, Dietrich WD, Vanni S, Wang MY, Levi AD (2013) Systemic hypothermia in acute cervical spinal cord injury: a case-controlled study. Spinal Cord 51:395–400
Diao C, Zhu L, Wang H (2003) Cooling and rewarming for brain ischemia or injury: theoretical analysis. Ann Biomed Eng 31:346–353
Diao C, Zhu L (2006) Temperature distribution and blood flow response in rat brain during selective brain cooling. Med Phys 33:2565–2573
Dixon SR, Whitbourn RJ, Dae MW, Grube E, Sherman W et al (2002) Induction of mild systemic hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction. J Am Coll Cardiol 40:1928–1934
Dietrich WD, Prado R, Halley M, Watson BD (1993) Microvascular and neuronal consequences of common carotid artery thrombosis and platelet embolization in rats. J Neuropathol Exp Neurol 52(4):351–360
Ding Y, Li J, Luan X, Lai Q, McAllister JP et al (2004) Local saline infusion into ischemic territory induces regional brain cooling and neuroprotection in rats with transient middle cerebral artery occlusion. Neurosurgery 54:956–965
Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischemia stroke: an integrated view. Trends Neurosci 22:391–397
Doufas AG, Akca O, Barry A, Petrusca DA, Suleman M et al (2002) Initial experience with a novel heat-exchanging catheter in neurosurgical patients. Anesth Analg 95:1752–1756
Drake CG, Jory TA (1962) Hypothermia in the treatment of critical head injury. Can Med Assoc J 87:887–891
Eginton ML (2007) Evaluation of the effectiveness of a commercial cooling collar in reducing body temperature during heat stress: theoretical modeling of body temperature distribution. Master’s thesis. University of Maryland, Baltimore County
Els T, Oehm E, Voigt S, Klisch J, Hetzel A, Kassubek J (2006) Safety and therapeutical benefit of hemicraniectomy combined with mild hypothermia in comparison with hemicraniectomy alone in patients with malignant ischemic stroke. Cerebrovasc Dis 21:79–85
Enomoto S, Hindman BJ, Dexter F, Smith T, Cutkomp J (1996) Rapid rewarming causes an increase in the cerebral metabolic rate for oxygen that is temporarily unmatched by cerebral blood flow. Anesthesiology 84:1392–1400
Esposito E, Ebner M, Ziemann U, Poli S (2014) In cold blood: intraarteral cold infusions for selective brain cooling in stroke. J Cereb Blood Flow Metab 34:743–752
Fay T (1945) Observations on generalized refrigeration in cases of severe cerebral trauma. Assoc Res Nerv Ment Dis Proc 4:611–619
Ferreira I, Schutte M, Oosterloo E et al (2009) Therapeutic hypothermia improves outcome after out-of-hospital cardiac arrest. Neth Heart J 17:378–384
Frank SM, Beattie C, Christopherson R et al (1993) Unintentional hypothermia is associated with postoperative myocardial ischemia. Anesthesiology 78:468–476
Fukuda T (2016) Targeted temperature management for adult out-of-hospital cardiac arrest: current concepts and clinical applications. J Intensive Care 4(1–8):30
Gal R, Cundrle I, Zimova I, Smrcka M (2002) Mild hypothermia therapy for patients with severe brain injury. Clin Neurol Neurosurg 104:318–321
Georgiadia D, Schwarz S, Kollmar R, Schwab S (2001) Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach. Stroke 32:2550–2553
Gillinov AM, Bator JM, Zehr KJ, Redmond JM, Burch RM et al (1993) Neutrophil adhesion molecule expression during cardiopulmonary bypass with bubble and membrane oxygenators. Ann Thorac Surg 56(4):847–853
Gong M, Ma W-G, Guan X-L, Wang L-F, Li J-C, Lan F, Sun L-Z, Zhang H-J (2016) Moderate hypothermic circulatory arrest in total arch repair for acute type a aortic dissection: clinical safety and efficacy. J Thorac Dis 8(5):925–933
Grahn DA, Brock-Utne JG, Watenpaugh DE, Heller HC (1998) Recovery from mild hypothermia can be accelerated by mechanically distending blood vessels in the hand. J Appl Physiol 85:1643–1648
Grahn DA, Cao VH, Heller HC (2005) Heat extraction through the palm of one hand improves aerobic exercise endurance in a hot environment. J Appl Physiol 99:972–978
Grahn D, Murray JLS, Watenpaugh DE, Heller HC (2008) Cooling via one hand improves physical performance in heat-sensitive individuals with Multiple Sclerosis: A preliminary study. BMC Neurol 8:14
Grulova I, Slovinska L, Nagyova M, Cizek M, Cizkova D (2013) The effect of hypothermia on sensory-motor function and tissue sparing after spinal cord injury. Spine J 13:1881–1891
Gunn AJ, Gunn TR (1998) The “pharmacology” of neuronal rescue with cerebral hypothermia. Early Hum Dev 53:19–35
Guo J, Wang Y, Zhu J, Cao J, Chen Z, Li Z, Qian X (2014) Right axillary and femoral artery perfusion with mild hypothermia for aortic arch replacement. J Cardiothorac Surg 9(1–6):94
Gutsche JT, Feinman J, Silvay G, Patel PA, Ghadimi K, Landoni G, Yue Y, augoustides JGT (2014) Practice variations in the conduct of hypothermic circulatory arrest for adult aortic arch repair: focus on an emerging European paradigm. Heart Lung Vessel 6(1):43–51
Ha KY, Kim YH (2008) Neuroprotective effect of moderate epidural hypothermia after spinal cord injury in rats. Spine 33:2059–2065
Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R (1996) “Malignant” middle cerebral artery territory infarction: clinical course and prognostic signs. Arch Neurol 53:309–315
Hansebout RR, Hansebout CR (2014) Local cooling for traumatic spinal cord injury: outcomes in 20 patients and review of the literature. J Neurosurg Spine 20(5):550–561
Harris BA, Andrews PJ, Murray GD (2007) Enhanced upper respiratory tract airflow and head fanning reduce brain temperature in brain-injured, mechanically ventilated patients: a randomized, crossover, factorial trial. Br J Anaesth 98:93–99
Hemmen TM, Raman R, Guluma KZ, Meyer BC, Gomes JA, Cruz-Flores S et al (2010) Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke(ICTuS-L): flinal results. Stroke 41:2265–2270
Hoffman W, Miletich DJ, Albrecht R (1982) Differential cerebral hypothermia. Cryobiology 19:392–401
Holzer M, Cerchiari E, Martens P, Roine R, Sterz F et al (2002) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346:549–556
Holzer M, Behringer W, Janata A, Bayegan K, Schima H et al (2005) Extracorporeal venovenous cooling for induction of mild hypothermia in human-sized swine. Crit Care Med 33:1346–1350
Hong JM, Lee JS, Song JH, Jeong HS, Choi HA et al (2014) Therapeutic hypothermia after recanalization in patients with acute ischemic stroke. Stroke 45:134–140
Hutchison JS, Ward RE, Lacroix J, Hébert PC, Barnes MA, Bohn DJ, Dirks PB, Doucette S, Fergusson D, Gottesman R, Joffe AR, Kirpalani HM, Meyer PG, Morris KP, Moher D, Singh RN, Skippen PW, for the Hypothermia Pediatric Head Injury Trial Investigators and the Canadian Critical Care Trials Group (2008) Hypothermia therapy after traumatic brain injury in children. N Engl J Med 358:2447–2456
Ibayashi S, Kakano K, Ooboshi H, Kitazono T (2000) Effect of selective brain hypothermia on regional cerebral blood flow and tissue metabolism using brain thermo-regulator in spontaneously hypertensive rats. Neurochem Res 25:369–375
Inderbitzen B, Yon S, Lasheras J, Dobak J, Perl J, Steinberg GK (2002) Safety and performance of a novel intravascular catheter for inducing and reversal of hypothermia in a porcine model. Neurosurgery 50:364–370
Jamieson SW, Kapelanski DP, Sakakibara N, Manecke GR, Thistlethwaite PA et al (2003) Coronary endarterectomy: experience and lessons learned in 1500 cases. Ann Thorac Surg 76(5):1457–1462
Janssen FEM, van Leeuwen GMJ, van Steenhoven AA (2005) Modeling of temperature and perfusion during scalp cooling. Phys Med Biol 50(17):4065–4073
Jiang JY, Yu MK, Zhu C (2000) Effect of long-term mild hypothermia therapy in patients with severe traumatic brain injury: 1-year follow-up review of 87 cases. J Neurosurg 93:546–549
Kabat H (1940) The greater resistance of very young animals to arrest of the brain circulation. Am J Phys 122:588–599
Kammersgaard LP, Rasmussen BH, Jorgensen HS, Reith J, Weber U, Olsen TS (2000) Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling: a case-control study. Stroke 31:2251–2256
Kasner SE, Wein T, Piryawat P, Villar-Cordove CE, Chalela JA et al (2002) Acetaminophen for altering body temperature in acute stroke: a randomized clinical trial. Editorial comment: a randomized clinical trial. Stroke 33:130–135
Kirkpatrick AW, Chun R, Brown R, Simons RK (1999) Hypothermia and the trauma patient. Can J Surg 42:333–343
Tisherman SA, Rodriguez A, Safar P (1999) Therapeutic hypothermia in traumatology. Surg Clin North Am 79:1269–1289
Kollmar R, Schellinger PD, Steigleder T, Kohrmann M, Schwab S (2009) Ice-cold saline for the induction of mild hypothermia in patients with acute ischemic stroke: a pilot study. Stroke 40:1907–1909
Konstas AA, Neimark MA, Laine AF, Pile-Spellman J (2007) A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain. J Appl Physiol 102:1329–1340
Kouchoukos NT, Daily BB, Wareing TH, Murphy SF (1994) Hypothermic circulatory arrest for cerebral protection during combined carotid and cardiac surgery in patients with bilateral carotid artery disease. Ann Surg 219(6):699–705
Krieger DW, De Georgia MA, Abou-Chebl A, Andrefsky JC, Sila CA et al (2001) Cooling for acute ischemic brain damage (COOL AID): an open pilot study of induced hypothermia in acute ischemic stroke. Stroke 32:1841–1854
Kuluz JW, Prado R, Chang J, Ginsberg MD, Schleien CL, Busto R (1993) Selective brain cooling increases cortical cerebral blood flow in rats. Am J Phys 265:H824–H827
Kurasako T, Zhan L, Pulsinelli WA, Nowak TS (2003) Transient cooling during early reperfusion attenuates delayed edema and infarct progression in the spontaneously hypertensive rat. Distribution and time course of regional brain temperature change in a model of postischemic hypothermic protection. J Cereb Blood Flow Metab 27:1919–1930
Laptook AR, Shalak L, Corbett RJT (2001) Differences in brain temperature and cerebral blood flow during selective head vs whole-body cooling. Pediatrics 108(5):1103–1110
Lauren I, Adrie C, vinsonneau C et al (2005) High-volume hemofiltration after out-of-hospital cardiac arrest: a randomized study. J Am Coll Cardiol 46:432–437
Lazorthes G, Campan L (1958) Hypothermia in the treatment of craniocerebral traumatism. J Neurosurg 15:162–167
Levi AD, Green BA, Wang MY, Dietrich WD, Brindle T, Vanni S et al (2009) Clinical application of modest intravascular hypothermia after spinal cord injury. J Neurotrauma 26:407–415
Levi AD, Casella G, Green BA, Dietrich WD, Vanni S, Jagid J et al (2010) Clinical outcomes using modest intrvascular hypothermia after acute cervical spinal cord injury. Neurosurgey 66:670–677
Ley O, Bayazitoglu Y (2003) Effect of physiology on the temperature distribution of a layered head with external convection. Int J Heat Mass Transf 46(17):3233–3241
Ley O, Bayazitoglu Y (2004) Temperature distribution in a realistic human head during selective and whole body cooling and during circulatory arrest. Proc. IMECE, IMECE2004–60733, Nov. 13–19. Anaheim, California
Li P, Yang C (2014) Moderate hypothermia treatment in adult patients with severe traumatic brain injury: a meta-analysis. Brain Inj 28:1036–1041
Liu WG, Qiu WS, Zhang Y, Wang WM, Lu F, Yang XF (2006) Effects of selective brain cooling in patients with severe traumatic brain injury: a preliminary study. J Int Med Res 34(1):58–64
Lo TP Jr, Cho KS, Garg MS, Lynch MP, Marcillo AE, Koivisto DL, Stagg M, Abril RM, Patel S, Dietrich WD (2009) Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats. J Comp Neurol 514:433–448
Mack WJ, Huang J, Winfree C, Kim G, Oppermann M et al (2003) Ultrarapid, convection-enhanced intravascular hypothermia: a feasibility study in nonhuman primate stroke. Stroke 34:1994–1999
Maekawa T, Yamashita S, Nagao S, Hayashi N, Ohashi Y, Brain-Hypothermia Study Group (2015) Prolonged mild therapeutic hypothermia versus fever control with tight hemodynamic monitoring and slow rewarming in patients with severe traumatic brain injury: a randomized controlled trial. J Neurotrauma 32:422–429
Markgraf CG, Clifton GL, Moody MR (2001) Treatment window for hypothermia in brain injury. J Neurosurg 95:979–983
Maier CM, Sun GH, Cheng D, Yenari MA, Chan PH, Steinberg GK (2002) Effects of mild hypothermia on superoxide anion production, superoxide dismutase expression, and activity following transient focal cerebral ischemia. Neurobiol Dis 11:28–42
Marion DW, Leonov Y, Ginsberg M, Katz LM, Kochanek PM et al (1996) Resuscitative hypothermia. Crit Care Med 24(suppl):S81–S89
Marion DW, Penrod LE, Kelsey SF, Obrist WD, Kochanek PM et al (1997) Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med 336:540–546
Maybhate A, Hu C, Bazley FA, Yu Q, Thakor NV, Kerr CL All AH (2012) Potential long-term benefits of acute hypothermia after spinal cord injury: assessments with somatosensory-evoked potentials. Crit Care Med 40:573–579
McIntyre LA, Fergusson DA, Hebert PC, Moher D, Hutchison JS (2003) Prolonged therapeutic hypothermia after traumatic brain injury in adults: a systematic review. JAMA 289:2992–2999
Meacham WF, McPherson WF (1973) Local hypothermia in the treatment of acute injuries of the spinal cord. South Med J 66:95–97
Metz C, Holzschuh M, Bein T, Woertgen C, Frey A et al (1996) Moderate hypothermia in patients with severe head injury: cerebral and extracerebral effects. J Neurosurg 85:533–541
Mellergard P, Nordstrom C, Christensson M (1990) A method for monitoring intracerebral temperature in neurosurgical patients. Neurosurgery 27:654–657
Michenfelder J (1988) Protecting the brain. In: Michenfelder J (ed) Anesthesia and the brain. Clinical, functional, metabolic and vascular correlates, 1st edn. Churchill Livingstone, USA, pp 181–193
Miller JA (1949) Factors in neonatal resistance to anoxia. I. Temperature and survival of newborn Guinea pigs under anoxia. Science 110:113–114
Miller JH (1993) Partial replacement of an infected arterial graft by a new prosthetic polytetrafluoroethylene segment: a new therapeutic option. J Vasc Surg 17(3):546–558
Moomiaie RM, Gould G, Solomon D, Simmons J, Kim J, Botta D et al (2012) Novel intracranial brain cooling catheter to mitigate brain injuries. J Neurointerv Surg 4:130–133
Morino T, Ogata T, Takeba J, Yamamoto H (2008) Microglia inhibition is a target of mild hypothermic treatment after the spinal cord injury. Spinal Cord 46:425–431
Morikawa E, Ginsberg MD, Dietrich WD, Duncan RC, Kraydieh S et al (1992) The significance of brain temperature in focal cerebral ischemia: histopathological consequences of middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 12(3):380–389
Mouritzen CV, Anderson MN (1966) Mechanisms of ventricular fibrillation during hypothermia: relative change in myocardial refractory period and conduction velocity. J Thorac Cardiovasc Surg 51:579–584
Moyer DJ, Welsh FA, Zager EL (1992) Spontaneous cerebral hypothermia diminishes focal infarction in rat brain. Stroke 23(12):1812–1816
Negrin J Jr (1973) Spinal cord hypothermia in the neurosurgical management of the acute and chronic post-traumatic paraplegic patient. Paraplegia 10:336–343
Neimark MA, Konstas AA, Choi JH, Laine AF, Pile-Spellman J (2007a) Local control of temperature in a theoretical human model of selective brain cooling. Conf Proc IEEE Eng Med Biol Soc 2007:6349–6352
Neimark MA, Konstas AA, Laine AF, Pile-Spellman J (2007b) Integration of jugular venous return and circle of Willis in a theoretical human model of selective brain cooling. J Appl Physiol 103:1837–1847
Neimark MA, Konstas A, Choi JH, Laine AF, Pile-Spellman J (2008) Brain cooling maintenance with cooling cap following induction with intracarotid cold saline infusion: a quantitative model. J Theor Biol 253(2):333–344
Neimark MA, Konstas AA, Lee L, Laine AF, Pile-Spellman J, Choi J (2013) Brain temperature changes during selective cooling with endovascular intracarotid Intraarterial cold saline infusion: simulation using human data fitted with an integrated mathematical model. J Neurointerv Sur 5:165–171
Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Aneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Kober L, Langorgen J, Lilja G, Moller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H, Investigators TTMT (2013) Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med 369:2197–2206
Nussmeier NA (2002) A review of risk factors for adverse neurologic outcome after cardiac surgery. J Extra Corpor Technol 34:4–10
Oddo M, Schaller MD, Feihl F, Ribordy V, Liaudet I (2006) From evidence to clinical practice: effective implementation of thrapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care 34:1865–1873
Okubo K, Itoh S, Isobe K, Kusaka T, Nagano K et al (2001) Cerebral metabolism and regional blood flow during moderate systemic cooling in newborn piglets. Pediatr Int 43:496–501
Olsen TS, Weber UJ, Kammersgaard LP (2003) Therapeutic hypothermia for acute stroke. Lancet Neurol 2:410–416
Pennes HH (1948) Analysis of tissue and arterial blood temperatures in the resting human forearm. J Appl Physiol 1:93–122
Peterson K, Carson S, Carney N (2008) Hypothermia treatment for traumatic brain injury: a systematic review and meta-analysis. J Neurotrauma 25:62–71
Petrovic M, Panic G, Jovelic A et al (2011) Therapeutic hypothermia and neurological outcom after cardiac arrest. Vojnosanit Pregl 68:495–499
Polderman KH, Rijnsburger ER, Peerdeman SM, Birbes AR (2005) Induction of hypothermia in patients with various types of neurologic injury with use of large volumes of ice-cold intrvenous fluid. Crit Care Med 33:2744–2751
Poli S, Purrucker J, Priglinger M, Diedler J, Sykora M, Popp E et al (2013) Induction of cooling with a passive head and neck cooling device: effects on brain temperature after stroke. Stroke 44:708–713
Puccio AM, Fischer MR, Jankowitz BT, Yonas H, Darby JM, Okonkwo DO (2009) Induced normothermia attenuates intracranial hypertension and reduces fever burden after severe rraumatic brain injury. Neurocrit Care 11(1):82–87
Purdy PD, Novakovic RL, Giles BP, Miller SL, Riegel MS (2013) Spinal cord hypothermia without systemic hypothermia. Am J Neuroradiol 34(1):252–256
Qiu W, Liu W, Shen H, Wang W, Zhang Z et al (2005) Therapeutic effect of mild hypothermia on severe traumatic head injury. Chin J Traumatol 8:27–32
Roach GW, Kanchuger M, Mangano CM, Newman M, Nussmeier N et al (1996) Adverse cerebral outcomes after coronary bypass surgery. Multicenter study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation investigators. N Engl J Med 335:1857–1863
Rohrer MJ, Natale AM (1992) Effect of hypothermia on the coagulation cascade. Crit Care Med 20:1402–1405
Rosengart AJ, Zhu L, Schappeler T, Goldenberg FD (2009) Fever control in hospitalized stroke patients using simple intravenous fluid regimens – a theoretical evaluation. J Clin Neurosci 16(1):51–55
Safar P, Kochanek PM (2001) Comments on “lack of effect of induction of hypothermia after acute brain injury”. N Engl J Med 345:66
Saxena M, Young P, Pilcher D, Bailey M, Harrison D, Bellomo R et al (2015) Early temperature and mortality in critically ill patients with acute neurological diseases: trauma and stroke differ from infection. Intensive Care Med 41:823–832
Schenone AL, Cohen A, Patarroyo G, Harper L, Wang X, Shishehbor MH, Menon V, Duggal A (2016) Therapeutic hypothermia after cardiac arrest: a systematic review/meta-analysis exploring the impact of expanded criteria and targeted temperature. Resuscitation 108:102–110
Schwab S, Spranger M, Aschoff A, Steiner T, Hacke W (1997) Brain temperature monitoring and modulation in patients with severe MCA infarction. Neurology 48:762–767
Schwab S, Schwarz S, Aschoff A, Keller E, Hacke W (1998a) Moderate hypothermia and brain temperature in patients with severe middle cerebral artery infarction. Acta Neurochir 71(suppl):131–134
Schwab S, Schwarz S, Spranger M, Keller E, Bertram M, Hacke W (1998b) Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke 29:2461–2466
Schwab S, Georgiadis D, Berrouschot J, Schellinger PD, Graffagnino C, Mayer SA (2001) Feasibility and safety of moderate hypothermia after massive hemispheric infarction. Stroke 32(9):2033–2035
Sedzimir CB (1959) Therapeutic hypothermia in cases of head injury. J Neurosurg 16:407–414
Selker RG (1971) Icewater irrigation of the spinal cord. Surg Forum 22:411–413
Shaefi S, Mittel AM, Hyam JA, Boone MD, Chn CC, Kasper EM (2016) Hypothermia for severe traumatic brain injury in adults: recent lessons from randomized controlled trials. Surg Neurol Int 103(1–11):7
Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA et al (2005) Whole-body hypothermia for neonates with hypoxic--ischemic encephalopathy. N Engl J Med 353:1574–1584
Shibuya S, Miyamoto O, Janjua NA, Itano T, Mori S, Norimatsu H (2004) Post-traumatic moderate systemic hypothermia reduces TUNEL positive cells following spinal cord injury in rat. Spinal Cord 42:29–34
Shiozaki T, Sugimoto H, Taneda M, Yoshida H, Iwai A et al (1993) Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg 79:363–368
Slotboom J, Kiefer C, Brekenfeld C, Ozdoba C, Remonda L, Nedeltchev K et al (2004) Locally induced hypothermia for treatment of acute ischaemic stroke: a physical feasibility study. Neuroradiology 46:923–934
Slotboom J (2007) Localized therapeutic hypothermia in the brain for the treatment of ischemic stroke. J Appl Physiol 102:1303–1304
Smith K, Zhu L (2010a) Theoretical evaluation of a simple cooling pad in inducing hypothermia in spinal cord following traumatic injury. Med Biol Eng Comput 48(2):167–175
Smith K, Zhu L (2010b) Brain hypothermia induced by cooled spinal fluid using a cooling pad: theoretical analyses. Med Biol Eng Comput 48(8):783–789
Springborg JB, Springborg KK, Romner B (2013) First clinical experience with intranasal cooling for hyperthermia in brain-injured patients. Neurocrit Care 18:400–405
Steeves JD, Kramer K, Fawcett JW, Cragg J, Lammertse DP, Blight AR, Marion RJ, Ditunno JF Jr, Coleman WP, Geisler FH, Guest J, Jones L, Burns S, Schubert M, van Hedel HJ, Curt AEMSCI Study Group (2011) Extent of spontaneous motor recovery after traumatic cervical sensorimotor complete spinal cord injury. Spinal Cord 49:257–265
Sterz F, Safar P, Tisherman S, Radovsky A, Kuboyama K, Oku K (1991) Mild hypothermic cardiopulmonary resuscitation improves outcome after prolonged cardiac arrest in dogs. Crit Care Med 19(3):379–389
Stone JG, Young WL, Smith CR, Solomon RA, Wald A et al (1995) Do standard monitoring sites reflect true brain temperature when profound hypothermia is rapidly induced and reversed? Anesthesiology 82:344–351
Strauch JT, Lauten A, Spielvogel D, Rinke S, Zhang N, Weisz D, Bodian CA, Griepp RB (2004) Mild hypothermia protects the spinal cord from ischemic injury in a chronic porcine model. Eur J Cardiothorac Surg 25:708–715
Tator CH (1972) Acute spinal cord injury: a review of recnet studies of treatment and pathophysiology. Can Med Assoc J 107:143–145
Thoresen M, Wyatt J (1997) Keeping a cool head, posthypoxic hypothermia---an old idea revisited. Acta Paediatr 86:1029–1033
Tripathy S, Whitehead CF (2011) Endovascular cooling for severe hyperthermia in cervical spine injury. Neurocrit Care 15:525–528
Vandam DV, Burnap TK (1959a) Hypothermia (part 1). N Engl J Med 261:546–553
Vandam DV, Burnap TK (1959b) Hypothermia (part 2). N Engl J Med 261:595–603
Vanden Hoek TL, Kasza KE, Beiser DG, Abella BS, Franklin JE et al (2004) Induced hypothermia by central venous infusion: saline ice slurry vs chilled saline. Crit Care Med 32:S425–S431
Van Der Worp HB, Sena ES, Donnan GA, Howells DW, Macleod MR (2007) Hypothermia in animal models of acute ischemic stroke: a systematic review and meta-analysis. Brain 130:3063–3074
Van Leeuwen GMJ, Hand J, Lagendijk JW, Azzopardi V, Edwards AD (2000) Numerical modeling of temperature distributions within the neonatal head. Pediatr Res 48:351–356
Verhaegen MJJ, Todd MM, Hindman BJ, Warner DS (1993) Cerebral autoregulation during moderate hypothermia in rats. Stroke 24:407–414
Virkkunen I, Yli-Hankala A, Silfvast T (2004) Induction of therapeutic hypothermia after cardiac arrest in prehospital patients using ice-cold Ringer’s solution: a pilot study. Resuscitation 62(3):299–302
Wagner KR, Zuccarello M (2005) Local brain hypothermia for neuroprotection in stroke treatment and aneurysm repair. Neurol Res 27:238–245
Wang H, Olivero W, Lanzino G, Elkins W, Rose J, Honings D et al (2004) Rapid and selective cerebral hypothermia achieved using a cooling helmet. J Neurosurg 100:272–277
Wang J, Pearse DD (2015) Therapeutic hypothermia in spinal cord injury: the status of its use and open questions. Int J Mol Sci 16:16848–16879
Wang Y, Zhu L (2007) Selective brain hypothermia induced by an interstitial cooling device in human neck: theoretical analyses. Eur J Appl Physiol 101(1):31–40
Wang Y, Zhu L, Rosengart AJ (2008) Targeted brain hypothermia induced by an interstitial cooling device in the rat neck: experimental study and model validation. Int J Heat Mass Transfer 51:5662–5670
Wass CT, Lanier WL, Hofer RE, Scheithauer BW, Andrews AG (1995) Temperature changes of ≥1°C alter functional neurologic outcome and histopathology in a canine model of complete cerebral ischemia. Anesthesiology 83:325—335
Wass CT, Lanier WL (1996) Hypothermia-associated protection from ischemic brain injury: implications for patient management. Int Anesthesiol Clin 34(4):95–111
Wei G, Hartings JA, Tortella FC, Lu XM (2008) Extraluminal cooling of bilateral common carotid arteries as a method to achieve selective brain cooling for neuroprotection. J Neurotrauma 25:549–560
Welsh FA, Sims RE, Harris VA (1990) Mild hypothermia prevents ischemic injury in gerbil hippocampus. J Cereb Blood Flow Metab 10:557–563
Xu L, Yenari MA, Steinberg GK, Giffard RG (2002) Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade. J Cereb Blood Flow Metab 22:21–28
Yenari MA, Onley D, Hedehus M, deCrespigny A, Sun GH et al (2000) Diffusion- and perfusion-weighted magnetic resonance imaging of focal cerebral ischemia and cortical spreading depression under conditions of mild hypothermia. Brain Res 885:208–219
Yoshitake A, Mori A, Shimizu H, Ueda T, Kabei N, Hachiya T, Okano H, Yozu R (2004) Use of an epidural cooling catheter with a closed countercurrent lumen to protect against ischemic spinal cord injury in pigs. J Thorac Cardiovasc Surg 134:1220–1226
Yu CG, Jimenez O, Marcillo AE, Weider B, Bangerter K, Dietrich WD, Castro S, Yezierski RP, (2000) Beneficial effects of modest systemic hypothermia on locomotor function and histopathological damage following contusion-induced spinal cord injury in rats. J Neurosurg 93:85–93
Zeiner A, Muellner M, Frossard M, Janata K, Behringer W et al (1996a) Mild therapeutic hypothermia to improve neurological outcome after cardiac arrest---a pilot study. Circulation 94:I9–I10
Zeiner A, Mullner M, Sterz F, Frossard M, Laggner A (1996b) Mild resuscitative therapeutic hypothermia after cardiac arrest and its influence on hemodynamic parameters. Crit Care Med 24:A115
Zhao QJ, Zhang XG, Wang LX (2011) Mild hypothermia therapy reduces blood glucose and lactate and improves neurologic outcomes in patients with severe traumatic brain injury. J Crit Care 26:311–315
Zhu L (2000) Theoretical evaluation of contributions of both radial heat conduction and countercurrent heat exchange in selective brain cooling in humans. Ann Biomed Eng 28:269–277
Zhu L, Diao C (2001) Theoretical simulation of temperature distribution in the brain during mild hypothermia treatment for brain injury. Med Biol Eng Comput 39:681–687
Zhu L, Rosengart AJ (2008) Cooling penetration into normal and injured brain via intraparenchymal brain cooling probe: theoretical analyses. Heat Trans Eng 29(3):284–294
Zhu L, Schappeler T, Cordero-Tumangday C, Rosengart AJ (2009) Thermal interactions between blood and tissue: development of a theoretical approach in predicting body temperature during blood cooling/rewarming. Adv Numer Heat Transfer 3:197–219
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Zhu, L. (2018). Hypothermia Used in Medical Applications for Brain and Spinal Cord Injury Patients. In: Fu, B., Wright, N. (eds) Molecular, Cellular, and Tissue Engineering of the Vascular System. Advances in Experimental Medicine and Biology, vol 1097. Springer, Cham. https://doi.org/10.1007/978-3-319-96445-4_16
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