Intranasal Perfluorochemical Spray for Preferential Brain Cooling in Sheep
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Hypothermic brain protection has been linked to how rapidly cooling is initiated and how quickly and uniformly the therapeutic hypothermic zone (THZ) is reached. The nasopharyngeal (NP) approach is uniquely suited for preferential brain cooling due to anatomic proximity to the cerebral circulation, cavernous sinus, and carotid arteries. This study explores a novel NP cooling approach employing evaporative characteristics of aerosolized perfluorochemical (PFC).
Anesthetized, normotensive sheep (n = 30) were instrumented with temperature probes and vascular catheters, then randomized to NP approach (NP-PFC: PFC spray device; n = 24) or whole body surface (WBS: n = 6) cooling. Regional temperatures, vital signs, and blood chemistries were assessed serially. Two animals were exposed to double PFC flow rates and PFC was measured in blood during NP-PFC cooling to assess PFC uptake and elimination. Cooling rates were evaluated (ANOVA) as a function of method (NP-PFC versus WBS) and time to reach the brain THZ (i.e., ≤−3.5°C below baseline).
Independent of region, brain cooling was faster during NP-PFC versus WBS (P < 0.001). During NP-PFC, brain > vascular > rectal cooling rates (P < 0.001), brain to systemic temperature gradients were maintained, the brain THZ was reached within 15 min, and the NP epithelial surface appeared histologically intact. During WBS, brain versus systemic cooling rates were not significantly different and the brain THZ could not be reached within 2 h.
The NP-PFC procedure more rapidly induced preferential brain cooling as compared to WBC without adverse effects.
- Krieger DW, Yenari MA. Therapeutic hypothermia for acute ischemic stroke: what do laboratory studies teach us? Stroke 2004;35:1482–9. CrossRef
- The 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. CrossRef
- Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–63. CrossRef
- Schwab S, Schwarz S, Spranger M, Keller E, Bertram M, Hacke W. Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke 1998;29:2461–6.
- Marion DW, Leonov Y, Ginsberg M, Katz LM, Kochanek PM, Lechleuthner A, Nemoto EM, Obrist W, Safar P, Sterz F, Tisherman SA, White RJ, Xiao F, Zar H. Resuscitative hypothermia. Crit Care Med 1996;24:S81–9.
- Behringer W, Prueckner S, Safar P, Radovsky A, Kentner R, Stezoski SW, Henchir J, Tisherman SA. Rapid induction of mild cerebral hypothermia by cold aortic flush achieves normal recovery in a dog outcome model with 20-minute exsanguination cardiac arrest. Acad Emerg Med 2000;7:1341–8. CrossRef
- Kuboyama K, Safar P, Radovsky A, Tisherman SA, Stezoski SW, Alexander H. Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study. Crit Care Med 1993;21:1348–58. CrossRef
- 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. CrossRef
- Maclellan CL, Davies LM, Fingas MS, Colbourne F. The influence of hypothermia on outcome after intracerebral hemorrhage in rats. Stroke 2006;37:1266–70. CrossRef
- Maclellan CL, Girgis J, Colbourne F. Delayed onset of prolonged hypothermia improves outcome after intracerebral hemorrhage in rats. J Cereb Blood Flow Metab 2004;24:432–40. CrossRef
- Gupta R, Jovin TG, Krieger DW. Therapeutic hypothermia for stroke: do new outfits change an old friend? Expert Rev Neurother 2005;5:235–46. CrossRef
- Plattner O, Kurz A, Sessler DI, Ikeda T, Christensen R, Marder D, Clough D. Efficacy of intraoperative cooling methods. Anesthesiology 1997;87:1089–95. CrossRef
- Thoresen M, Whitelaw A. Therapeutic hypothermia for hypoxic-ischaemic encephalopathy in the newborn infant. Curr Opin Neurol 2005;18:111–6. CrossRef
- Hachimi-Idrissi S, Corne L, Ebinger G, Michotte Y, Huyghens L. Mild hypothermia induced by a helmet device: a clinical feasibility study. Resuscitation 2001;51:275–81. CrossRef
- Wang H, Olivero W, Lanzino G, Elkins W, Rose J, Honings D, Rodde M, Burnham J, Wang D. Rapid and selective cerebral hypothermia achieved using a cooling helmet. J Neurosurg 2004;100:272–7. CrossRef
- De Georgia MA, Krieger DW, Abou-Chebl A, Devlin TG, Jauss M, Davis SM, Koroshetz WJ, Rordorf G, Warach S. Cooling for Acute Ischemic Brain Damage (COOL AID): a feasibility trial of endovascular cooling. Neurology 2004;63:312–7.
- Krieger DW, De Georgia MA, Abou-Chebl A, Andrefsky JC, Sila CA, Katzan IL, Mayberg MR, Furlan AJ. Cooling for acute ischemic brain damage (cool aid): an open pilot study of induced hypothermia in acute ischemic stroke. Stroke 2001;32:1847–54.
- Mori K, Saito J, Kurata Y, Takeyama Y, Itoh Y, Kaneko M, Asai Y, Renzi FP, Dickson EW. Rapid development of brain hypothermia using femoral-carotid bypass. Acad Emerg Med 2001;8:303–8. CrossRef
- Vanden Hoek TL, Kasza KE, Beiser DG, Abella BS, Franklin JE, Oras JJ, Alvarado JP, Anderson T, Son H, Wardrip CL, Zhao D, Wang H, Becker LB. Induced hypothermia by central venous infusion: saline ice slurry versus chilled saline. Crit Care Med 2004;32:S425–31. CrossRef
- Straub JA, Chickering DE, Hartman TG, Gloff CA, Bernstein H. AI-700 pharmacokinetics, tissue distribution and exhaled elimination kinetics in rats. Int J Pharm 2007;328:35–41. CrossRef
- Ginsberg MD, Busto R. Combating hyperthermia in acute stroke: a significant clinical concern. Stroke 1998;29:529–34.
- Baena RC, Busto R, Dietrich WD, Globus MY, Ginsberg MD. Hyperthermia delayed by 24 hours aggravates neuronal damage in rat hippocampus following global ischemia. Neurology 1997;48:768–73.
- Kim Y, Busto R, Dietrich WD, Kraydieh S, Ginsberg MD. Delayed postischemic hyperthermia in awake rats worsens the histopathological outcome of transient focal cerebral ischemia. Stroke 1996;27:2274–80.
- Maloney SK, Mitchell D, Blache D. The contribution of carotid rete variability to brain temperature variability in sheep in a thermoneutral environment. Am J Physiol Regul Integr Comp Physiol 2007;292:R1298–305.
- Mitchell D, Maloney SK, Jessen C, Laburn HP, Kamerman PR, Mitchell G, Fuller A. Adaptive heterothermy and selective brain cooling in arid-zone mammals. Comp Biochem Physiol B Biochem Mol Biol 2002;131:571–85. CrossRef
- Cabanac M. Selective brain cooling in humans: “fancy” or fact? FASEB J 1993;7:1143–6.
- Mariak Z, White MD, Lewko J, Lyson T, Piekarski P. Direct cooling of the human brain by heat loss from the upper respiratory tract. J Appl Physiol 1999;87:1609–13.
- Schwab S, Spranger M, Aschoff A, Steiner T, Hacke W. Brain temperature monitoring and modulation in patients with severe MCA infarction. Neurology 1997;48:762–7.
- Zeiner A, Holzer M, Sterz F, Behringer W, Schorkhuber W, Mullner M, Frass M, Siostrzonek P, Ratheiser K, Kaff A, Laggner AN. Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. A clinical feasibility trial. Hypothermia After Cardiac Arrest (HACA) Study Group. Stroke 2000;31:86–94.
- Mayer SA, Kowalski RG, Presciutti M, Ostapkovich ND, McGann E, Fitzsimmons BF, Yavagal DR, Du YE, Naidech AM, Janjua NA, Claassen J, Kreiter KT, Parra A, Commichau C. Clinical trial of a novel surface cooling system for fever control in neurocritical care patients. Crit Care Med 2004;32:2508–15. CrossRef
- Furuse M, Preul MC, Kinoshita Y, Nishihara K, Isono N, Kuroiwa T. Rapid induction of brain hypothermia by endovascular intra-arterial perfusion. Neurol Res 2007;29:53–7. CrossRef
- Steinberg GK, Ogilvy CS, Shuer LM, Connolly ES Jr, Solomon RA, Lam A, Kassell NF, Baker CJ, Giannotta SL, Cockroft KM, Bell-Stephens TE, Allgren RL. Comparison of endovascular and surface cooling during unruptured cerebral aneurysm repair. Neurosurgery 2004;55:307–14. CrossRef
- Janata A, Holzer M, Bayegan K, Frossard M, Sterz F, Losert UM, Laggner AN, Behringer W. Rapid induction of cerebral hypothermia by aortic flush during normovolemic cardiac arrest in pigs. Crit Care Med 2006;34:1769–74. CrossRef
- Wu X, Drabek T, Kochanek PM, Henchir J, Stezoski SW, Stezoski J, Cochran K, Garman R, Tisherman SA. Induction of profound hypothermia for emergency preservation and resuscitation allows intact survival after cardiac arrest resulting from prolonged lethal hemorrhage and trauma in dogs. Circulation 2006;113:1974–82. CrossRef
- Zikria BA, Ferrer JM, Malm JR. Pulmonary hypothermia in dogs. J Appl Physiol 1968;24:707–10.
- Harrison MR, Hysing ES, Bo G. Control of body temperature: use of the respiratory tract as a heat exchanger. J Pediatr Surg 1977;12:821–8. CrossRef
- Beran AV, Sperling DR. An improved method for inducing hypothermia and rewarming. Aviat Space Environ Med 1979;50:844–6.
- Piantadosi CA, Thalmann ED. Thermal responses in humans exposed to cold hyperbaric helium-oxygen. J Appl Physiol 1980;49:1099–106.
- Ingenito E, Solway J, Lafleur J, Lombardo A, Drazen JM, Pichurko B. Dissociation of temperature-gradient and evaporative heat loss during cold gas hyperventilation in cold-induced asthma. Am Rev Respir Dis 1988;138:540–6.
- Andrews PJ, Harris B, Murray GD. 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 2005;94:330–5. CrossRef
- Harris BA, Andrews PJ, Murray GD. 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 2007;98:93–9. CrossRef
- Corno C, Fiore GB, Martelli E, Dani C, Costantino ML. Volume controlled apparatus for neonatal tidal liquid ventilation. ASAIO J 2003;49:250–8. CrossRef
- Shaffer TH, Forman DL, Wolfson MR. Physiological effects of ventilation with liquid fluorocarbon at controlled temperatures. Undersea Biomed Res 1984;11(3):287–98.
- Forman DL, Bhutani VK, Tran N, Shaffer TH. A new approach to induced hypothermia. J Surg Res 1986;40:36–42. CrossRef
- Harris SB, Darwin MG, Russell SR, O’Farrell JM, Fletcher M, Wowk B. Rapid (0.5 degrees C/min) minimally invasive induction of hypothermia using cold perfluorochemical lung lavage in dogs. Resuscitation 2001;50:189–204. CrossRef
- Hong SB, Koh Y, Shim TS, Lee SD, Kim WS, Kim DS, Kim WD, Lim CM. Physiologic characteristics of cold perfluorocarbon-induced hypothermia during partial liquid ventilation in normal rabbits. Anesth Analg 2002;94:157–62. CrossRef
- Yang SS, Jeng MJ, McShane R, Chen CY, Wolfson MR, Shaffer TH. Cold perfluorochemical-induced hypothermia protects lung integrity in normal rabbits. Biol Neonate 2005;87:60–5. CrossRef
- Mates EA, Hildebrandt J, Jackson JC, Tarczy-Hornoch P, Hlastala MP. Shunt and ventilation-perfusion distribution during partial liquid ventilation in healthy piglets. J Appl Physiol 1997;82:933–42.
- Thoresen M, Satas S, Loberg EM, Whitelaw A, Acolet D, Lindgren C, Penrice J, Robertson N, Haug E, Steen PA. Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic-ischemic insult is not neuroprotective. Pediatr Res 2001;50:405–11. CrossRef
- Mellergard P. Changes in human intracerebral temperature in response to different methods of brain cooling. Neurosurgery 1992;31:671–7. CrossRef
- Gunn AJ, Gunn TR. The ‘pharmacology’ of neuronal rescue with cerebral hypothermia. Early Hum Dev 1998;53:19–35. CrossRef
- Gunn AJ, Gluckman PD, Gunn TR. Selective head cooling in newborn infants after perinatal asphyxia: a safety study. Pediatrics 1998;102:885–92. CrossRef
- Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005;365:663–70.
- Horn AR, Woods DL, Thompson C, Eis I, Kroon M. Selective cerebral hypothermia for post-hypoxic neuroprotection in neonates using a solid ice cap. S Afr Med J 2006;96:976–81.
- Thoresen M, Simmonds M, Satas S, Tooley J, Silver IA. Effective selective head cooling during posthypoxic hypothermia in newborn piglets. Pediatr Res 2001;49:594–9. CrossRef
- Hagioka S, Takeda Y, Takata K, Morita K. Nasopharyngeal cooling selectively and rapidly decreases brain temperature and attenuates neuronal damage, even if initiated at the onset of cardiopulmonary resuscitation in rats. Crit Care Med 2003;31:2502–8. CrossRef
- Shaffer TH, Foust R, Wolfson MR, Miller TF Jr. Analysis of perfluorochemical elimination from the respiratory system. J Appl Physiol 1997;83:1033–40.
- Kechner N. Factors effecting perfluorochemical uptake into the blood following exposure to liquid assisted ventilation. Temple University School of Medicine; 1997. p. 1–209.
- Miller TF, Milestone B, Stern R, Shaffer TH, Wolfson MR. Effects of perfluorochemical distribution and elimination dynamics on cardiopulmonary function. J Appl Physiol 2001;90:839–49.
- Wolfson MR, Kechner NE, Roache RF, Dechadarevian JP, Friss HE, Rubenstein SD, Shaffer TH. Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency. J Appl Physiol 1998;84:624–40.
- Cox CA, Stavis L, Wolfson MR, Shaffer TH. Long-term tidal liquid ventilation in premature lambs: physiologic, biochemical and histological correlates. Biol Neonate 2003;84:232–42. CrossRef
- Shaffer TH, Wolfson MR, Greenspan JS, Hoffman RE, Davis SL, Clark LC Jr. Liquid ventilation in premature lambs: uptake, biodistribution and elimination of perfluorodecalin liquid. Reprod Fertil Dev 1996;8:409–16. CrossRef
- Wolfson MR, Greenspan JS, Shaffer TH. Liquid-assisted ventilation: an alternative respiratory modality. Pediatr Pulmonol 1998;26:42–63. CrossRef
- Modell JH, Calderwood HW, Ruiz BC, Tham MK, Hood CI. Liquid ventilation of primates. Chest 1976;69(1):79–81. CrossRef
- Holaday DA, Fiserova-Bergerova V, Modell JH. Uptake, distribution, and excretion of fluorocarbon FX-80 (perfluorobutyl perfluorotetrahydrofuran) during liquid breathing in the dog. Anesthesiology 1972;37:387–94. CrossRef
- Hood CI, Modell JH. A morphologic study of long-term retention of fluorocarbon after liquid ventilation. Chest 2000;118:1436–40. CrossRef
- Riess JG. Overview of progress in the fluorocarbon approach to in vivo oxygen delivery [Review]. Artif Cells Blood Substit Immobil Biotechnol 1992;20:20–4.
- Riess JG, LeBlanc M. Solubility and transport phenomeno in perfluorochemical relevant to blood substitution and other biomedical applications. Pure Appl Chem 1982;54:2383–406. CrossRef
- Keipert PE, Otto S, Flaim SF, Weers JG, Schutt EA, Pelura TJ, Klein DH, Yaksh TL. Influence of perflubron emulsion particle size on blood half-life and febrile response in rats. Artic Cells Blood Substit Immobil Biotechnol 1994;22:1169–74. CrossRef
- Intranasal Perfluorochemical Spray for Preferential Brain Cooling in Sheep
Volume 8, Issue 3 , pp 437-447
- Cover Date
- Print ISSN
- Online ISSN
- Humana Press Inc
- Additional Links
- Whole body cooling
- Preferential brain cooling
- Nasopharyngeal cooling
- Perfluorochemical liquids
- Industry Sectors
- Author Affiliations
- 1. Department of Physiology & Pediatrics, Temple University School of Medicine, 3420 N Broad Street, Philadelphia, PA, 19140, USA
- 2. BeneChill Inc., San Diego, CA, USA
- 3. Nemours Lung Center, Alfred I. DuPont Hospital, Wilmington, DE, USA