Research Article

Brain changes in Hypothermia: Surface-versus Core-cooling in pigs

Inge Morild*, Kåre Lilleng, Stig Morten Hammersborg and Paul Husby

Published: 31 October, 2017 | Volume 1 - Issue 2 | Pages: 092-097

The process of hypothermia in the clinical setting has been practiced for 50 years and is known for its neuroprotective properties. This paper describes histopathological changes either by an ice sludge mimicking accidental hypothermia (S-group n=7) or by endovascular core-cooling (C-group n=7). Focal infiltrates of neutrophilic granulocytes were found in five of seven brains in the S-group and in one of seven brains in the C-group. These granulocytes were found in the arachnoids, in vessels, in vessel walls, and in the cerebral cortex. Fungi, bacteria, lymphocytes or plasma were not found.

This experimental study, mimicking accidental hypothermia, reported histopathologic features of aseptic inflammation. To our knowledge, such findings have not been described in hypothermic animals or humans before. We suggest that a local inflammatory response may be triggered in such cases of hypothermia.

Read Full Article HTML DOI: 10.29328/journal.jfsr.1001011 Cite this Article Read Full Article PDF


Hypothermia; Surface cooling; Core cooling; Pigs; Histopathology; Aseptic meningitis; Cerebral micro dialysis


  1. Eisenburger P, Sterz F, Holzer M, Zeiner A, Scheinecker W, et al. Therapeutic hypothermia after cardiac arrest. Curr Opin Crit Care. 2001; 7: 184-188. Ref.: https://goo.gl/brTWx9
  2. Nilsson L, Kogure K, Busto R. Effects of hypothermia and hyperthermia on brain energy metabolism. Acta Anaesthesiol Scand. 1975; 19: 199-205. Ref.: https://goo.gl/iD6LGH
  3. Moore EM, Nichol AD, Bernard SA, Bellomo R. Therapeutic hypothermia: benefits, mechanisms and potential clinical applications in neurological, cardiac and kidney injury. Injury. 2011; 42: 843-854. Ref.: https://goo.gl/eBMjSu
  4. Hammersborg SM, Farstad M, Haugen O, Kvalheim V, Onarheim H, et al. Time course variations of haemodynamics, plasma volume and microvascular fluid exchange following surface cooling: an experimental approach to accidental hypothermia. Resuscitation. 2005; 65: 211-219. Ref.: https://goo.gl/6jYLBi
  5. Farstad M, Heltne JK, Rynning SE, Lund T, Mongstad A, et al. Fluid extravasation during cardiopulmonary bypass in piglets-effects of hypothermia and different cooling protocols. Acta Anaesthesiol Scand. 2003; 47: 397-406. Ref.: https://goo.gl/a4xDMx
  6. Lofstrom B. Induced hypothermia and intravascular aggregation. Acta Anaesthesiol Scand. 1959; 3: 1-19. Ref.: https://goo.gl/4qiox3
  7. Endrich B, Hammersen F, Messmer K. Microvascular ultrastructure in non-freezing cold injuries. Res Exp Med. 1990; 190: 365-379. Ref.: https://goo.gl/L2hLA1
  8. Hammersborg SM, Brekke HK, Haugen O, Farstad M, Husby P. Surface cooling versus core cooling: comparative studies of microvascular fluid- and protein-shifts in a porcine model. Resuscitation. 2008; 79: 292-300. Ref.: https://goo.gl/pxxLXa
  9. Schwartz BG, Kloner RA, Thomas JL, Bui Q, Mayeda GS, et al. Therapeutic Hypothermia for Acute Myocardial Infarction and Cardiac Arrest. Am J Cardiol. 2012; 110: 461-466. Ref.: https://goo.gl/31wyyk
  10. Kramer C, Freeman WD, Larson JS, Hoffman-Snyder C, Wellik KE, et al. Therapeutic hypothermia for severe traumatic brain injury: a critically appraised topic. Neurologist. 2012; 18: 173-177. Ref.: https://goo.gl/VwGsvx
  11. Lakhan SE, Pamplona F. Application of mild therapeutic hypothermia on stroke: a systematic review and meta-analysis. Stroke Res Treat. 2012. Ref.: https://goo.gl/odrzQF
  12. Lampe JW, Becker LB. State of the art in therapeutic hypothermia. Annu Rev Med. 2011; 62: 79-93. Ref.: https://goo.gl/ufJWiA
  13. Delhaye C, Mahmoudi M, Waksman R. Hypothermia therapy: neurological and cardiac benefits. J Am Coll Cardiol. 2012; 59: 197-210. Ref.: https://goo.gl/x4hqv7
  14. Kvalheim VL, Farstad M, Steien E, Mongstad A, Borge BA, et al. Infusion of hypertonic saline/starch during cardiopulmonary bypass reduces fluid overload and may impact cardiac function. Acta Anaesthesiol Scand. 2010; 54: 485-493. Ref.: https://goo.gl/Vx5uUm
  15. Haugen O, Farstad M, Myklebust R, Kvalheim V, Hammersborg S, et al. Low perfusion pressure during CPB may induce cerebral metabolic and ultrastructural changes. Scand Cardiovasc J. 2007; 41: 331-338. Ref.: https://goo.gl/n4mkHJ
  16. Lemasters JJ, Theruvath TP, Zhong Z, Nieminen AL. Mitochondrial calcium and the permeability transition in cell death. Biochim Biophys Acta. 2009; 1787: 1395-401. Ref.: https://goo.gl/XKEoKv
  17. Hannon JP, Bossone CA, Wade CE. Normal physiological values for conscious pigs used in biomedical research. Lab Anim Sci. 1990; 40: 293-298. Ref.: https://goo.gl/zEz9gT
  18. Iwata O, Iwata S, Tamura M, Nakamura T, Sugiura M, et al. Early head cooling in newborn piglets is neuroprotective even in the absence of profound systemic hypothermia. Pediatr Int. 2003; 45: 522-529. Ref.: https://goo.gl/zVEcvG
  19. Iwata S, Iwata O, Thornton JS, Shanmugalingam S, Bainbridge A, et al. Superficial brain is cooler in small piglets: neonatal hypothermia implications. Ann Neurol. 2006; 60: 578-585. Ref.: https://goo.gl/mQQNNh
  20. Prandini MN, Neves Filho A, Lapa AJ, Stavale JN. Mild hypothermia reduces polymorphonuclear leukocytes infiltration in induced brain inflammation. Arq Neuropsiquiatr. 2005; 63: 779-784. Ref.: https://goo.gl/xnAiHd


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