Regional hypothermia improves gastric microcirculatory oxygenation during hemorrhage in dogs

Autoři: Richard Truse aff001;  Michael Smyk aff001;  Jan Schulz aff001;  Anna Herminghaus aff001;  Andreas P. M. Weber aff002;  Tabea Mettler-Altmann aff002;  Inge Bauer aff001;  Olaf Picker aff001;  Christian Vollmer aff001
Působiště autorů: Department of Anesthesiology, Duesseldorf University Hospital, Duesseldorf, Germany aff001;  Institute of Plant Biochemistry, Cluster of Excellence on Plant Sciences (CEPLAS), Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


Mild systemic hypothermia increases gastric mucosal oxygenation (μHbO2) during hemorrhagic shock in dogs. In the context of critical blood loss hypothermia might be fatal due to adverse side effects. Selective regional hypothermia might overcome these limitations. The aim of our study was to analyze the effects of regional gastric and oral mucosal hypothermia on μHbO2 and perfusion (μflow). In a cross-over study six anesthetized dogs were subjected to local oral and gastric mucosal hypothermia (34°C), or maintenance of local normothermia during normovolemia and hemorrhage (-20% blood volume). Macro- and microcirculatory variables were recorded continuously. During normovolemia, local hypothermia increased gastric microcirculatory flow (μflow) without affecting oxygenation (μHbO2) or oral microcirculation. During mild hemorrhagic shock gastric μHbO2 decreased from 72±2% to 38±3% in the normothermic group. This was attenuated by local hypothermia, where μHbO2 was reduced from 74±3% to 52±4%. Local perfusion, oral microcirculation and macrocirculatory variables were not affected. Selective local hypothermia improves gastric μHbO2 during hemorrhagic shock without relevant side effects. In contrast to systemic hypothermia, regional mucosal hypothermia did not affect perfusion and oxygen supply during hemorrhage. Thus, the increased μHbO2 during local hypothermia rather indicates reduced mucosal oxygen demand.

Klíčová slova:

Blood – Dogs – Hypothermia – Microcirculation – Oxygen – Severe blood loss – Sucrose


1. Haagsma JA, Graetz N, Bolliger I, Naghavi M, Higashi H, Mullany EC, et al. The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013. Inj Prev. 2016 Feb 1;22(1):3–18. doi: 10.1136/injuryprev-2015-041616 26635210

2. Lansink KWW, Gunning AC, Leenen LPH. Cause of death and time of death distribution of trauma patients in a Level I trauma centre in the Netherlands. Eur J Trauma Emerg Surg. 2013 Aug 1;39(4):375–83. doi: 10.1007/s00068-013-0278-2 26815398

3. Brattström O, Granath F, Rossi P, Oldner A. Early predictors of morbidity and mortality in trauma patients treated in the intensive care unit. Acta Anaesthesiol Scand. 2010 Sep;54(8):1007–17. doi: 10.1111/j.1399-6576.2010.02266.x 20626360

4. Deitch EA, Xu D, Kaise VL. Role of the gut in the development of injury- and shock induced SIRS and MODS: the gut-lymph hypothesis, a review. Front Biosci J Virtual Libr. 2006 Jan 1;11:520–8.

5. Schörghuber M, Fruhwald S. Effects of enteral nutrition on gastrointestinal function in patients who are critically ill. Lancet Gastroenterol Hepatol. 2018;3(4):281–7. doi: 10.1016/S2468-1253(18)30036-0 29533200

6. Patel JJ, Rosenthal MD, Miller KR, Martindale RG. The gut in trauma. Curr Opin Crit Care. 2016;22(4):339–46. doi: 10.1097/MCC.0000000000000331 27314259

7. Karnatovskaia LV, Wartenberg KE, Freeman WD. Therapeutic Hypothermia for Neuroprotection. The Neurohospitalist. 2014 Jul;4(3):153–63. doi: 10.1177/1941874413519802 24982721

8. Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009 Oct 1;361(14):1349–58. doi: 10.1056/NEJMoa0900854 19797281

9. Ly HQ, Denault A, Dupuis J, Vadeboncoeur A, Harel F, Arsenault A, 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 Nov;150(5):933.

10. Koreny M, Sterz F, Uray T, Schreiber W, Holzer M, Laggner A, et al. Effect of cooling after human cardiac arrest on myocardial infarct size. Resuscitation. 2009 Jan;80(1):56–60. doi: 10.1016/j.resuscitation.2008.08.019 18951682

11. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002 Feb 21;346(8):549–56. doi: 10.1056/NEJMoa012689 11856793

12. Donnino MW, Andersen LW, Berg KM, Reynolds JC, Nolan JP, Morley PT, et al. Temperature Management After Cardiac Arrest: An Advisory Statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation. Resuscitation. 2016 Jan 1;98:97–104. doi: 10.1016/j.resuscitation.2015.09.396 26449873

13. Vollmer C, Schwartges I, Swertz M, Beck C, Bauer I, Picker O. Hypothermia improves oral and gastric mucosal microvascular oxygenation during hemorrhagic shock in dogs. Oxid Med Cell Longev. 2013;2013:589606. doi: 10.1155/2013/589606 24327826

14. Vollmer C, Nommensen J, Watolla M, Bauer I, Picker O. Influence of thoracic epidural anesthesia on gastric oxygenation during hypothermia and hemorrhage. Auton Neurosci Basic Clin. 2016 Feb;195:1–7.

15. Vollmer C, Weiß S, Beck C, Bauer I, Picker O. Hypothermia improves oral and gastric mucosal oxygenation during hypoxic challenges. Br J Anaesth. 2014 Sep;113(3):433–42. doi: 10.1093/bja/aet462 24390551

16. Ferrara A, MacArthur JD, Wright HK, Modlin IM, McMillen MA. Hypothermia and acidosis worsen coagulopathy in the patient requiring massive transfusion. Am J Surg. 1990 Nov 1;160(5):515–8. doi: 10.1016/s0002-9610(05)81018-9 2240386

17. Jurkovich GJ, Greiser WB, Luterman A, Curreri PW. Hypothermia in trauma victims: an ominous predictor of survival. J Trauma. 1987 Sep;27(9):1019–24. 3656464

18. Bro-Jeppesen J, Kjaergaard J, Søholm H, Wanscher M, Lippert FK, Møller JE, et al. Hemodynamics and vasopressor support in therapeutic hypothermia after cardiac arrest: prognostic implications. Resuscitation. 2014 May;85(5):664–70. doi: 10.1016/j.resuscitation.2013.12.031 24412644

19. Truse R, Hinterberg J, Schulz J, Herminghaus A, Weber A, Mettler-Altmann T, et al. Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs. J Vasc Res. 2017;54(2):109–21. doi: 10.1159/000464262 28441653

20. Kim J-H, Yun S-H, Jang K-H, Park J, Han HS, Rhee D, et al. Delayed and prolonged local brain hypothermia combined with decompressive craniectomy: a novel therapeutic strategy that modulates glial dynamics. Exp Neurobiol. 2014 Jun;23(2):115–23. doi: 10.5607/en.2014.23.2.115 24963275

21. Schwartz DS, Bremner RM, Baker CJ, Uppal KM, Barr ML, Cohen RG, et al. Regional topical hypothermia of the beating heart: preservation of function and tissue. Ann Thorac Surg. 2001 Sep;72(3):804–9. doi: 10.1016/s0003-4975(01)02822-3 11565662

22. Schwartges I, Picker O, Beck C, Scheeren TWL, Schwarte LA. Hypercapnic acidosis preserves gastric mucosal microvascular oxygen saturation in a canine model of hemorrhage. Shock Augusta Ga. 2010 Dec;34(6):636–42.

23. Dyson DH. Positive pressure ventilation during anesthesia in dogs: Assessment of surface area derived tidal volume. Can Vet J Rev Vét Can. 2012 Jan;53(1):63–6.

24. Krug A. CME: Mikrozirkulation und Sauerstoffversorgung des Gewebes—Methode des so genannten O2C (oxygen to see). Phlebologie. 2006;35(6):300–12.

25. Sato N, Kawano S, Kamada T, Takeda M. Hemodynamics of the gastric mucosa and gastric ulceration in rats and in patients with gastric ulcer. Dig Dis Sci. 1986 Feb;31(2 Suppl):35S–41S. doi: 10.1007/bf01309321 3943456

26. Aykut G, Veenstra G, Scorcella C, Ince C, Boerma C. Cytocam-IDF (incident dark field illumination) imaging for bedside monitoring of the microcirculation. Intensive Care Med Exp [Internet]. 2015 Jan 31 [cited 2017 Feb 15];3. Available from:

27. De Backer D, Hollenberg S, Boerma C, Goedhart P, Büchele G, Ospina-Tascon G, et al. How to evaluate the microcirculation: report of a round table conference. Crit Care. 2007;11(5):R101. doi: 10.1186/cc6118 17845716

28. Carsetti A, Pierantozzi S, Aya H, Bazurro S, Donati A, Rhodes A, et al. Accuracy of an automatic analysis software to detect microvascular density parameters. Intensive Care Med Exp [Internet]. 2015 Oct 1 [cited 2017 Feb 13];3(Suppl 1). Available from:

29. Bezemer R, Bartels SA, Bakker J, Ince C. Clinical review: Clinical imaging of the sublingual microcirculation in the critically ill—where do we stand? Crit Care Lond Engl. 2012 Jun 19;16(3):224.

30. Meddings JB, Sutherland LR, Byles NI, Wallace JL. Sucrose: a novel permeability marker for gastroduodenal disease. Gastroenterology. 1993 Jun;104(6):1619–26. doi: 10.1016/0016-5085(93)90637-r 8500718

31. Fiehn O, Kind T. Metabolite profiling in blood plasma. Methods Mol Biol Clifton NJ. 2007;358:3–17.

32. Kortbeek JB, Al Turki SA, Ali J, Antoine JA, Bouillon B, Brasel K, et al. Advanced trauma life support, 8th edition, the evidence for change. J Trauma. 2008 Jun;64(6):1638–50. doi: 10.1097/TA.0b013e3181744b03 18545134

33. Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175–91. doi: 10.3758/bf03193146 17695343

34. Schumacker PT, Rowland J, Saltz S, Nelson DP, Wood LD. Effects of hyperthermia and hypothermia on oxygen extraction by tissues during hypovolemia. J Appl Physiol Bethesda Md 1985. 1987 Sep;63(3):1246–52.

35. Gutierrez G, Warley AR, Dantzker DR. Oxygen delivery and utilization in hypothermic dogs. J Appl Physiol Bethesda Md 1985. 1986 Mar;60(3):751–7.

36. Leone BJ, Watke CM, Osgood CF, Richardson KM, Brittin KB, White WD, et al. Effect of mild hypothermia during cardiopulmonary bypass on erythrocytic hemoglobin oxygen delivery. J Cardiothorac Vasc Anesth. 1998 Aug;12(4):393–6. doi: 10.1016/s1053-0770(98)90190-2 9713725

37. Erecinska M, Thoresen M, Silver IA. Effects of hypothermia on energy metabolism in Mammalian central nervous system. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2003 May;23(5):513–30.

38. Steen PA, Newberg L, Milde JH, Michenfelder JD. Hypothermia and barbiturates: individual and combined effects on canine cerebral oxygen consumption. Anesthesiology. 1983 Jun;58(6):527–32. 6859582

39. Xiong W, Xu S, Li H, Liang K. Moderate hypothermia ameliorates enterocyte mitochondrial dysfunction in severe shock and reperfusion. J Surg Res. 2016 Jan;200(1):250–9. doi: 10.1016/j.jss.2015.06.068 26227675

40. Sutherland LR, Verhoef M, Wallace JL, Van Rosendaal G, Crutcher R, Meddings JB. A simple, non-invasive marker of gastric damage: sucrose permeability. Lancet. 1994 Apr 23;343(8904):998–1000. doi: 10.1016/s0140-6736(94)90125-2 7909091

41. Van den Brande P, De Coninck A, Lievens P. Skin microcirculation responses to severe local cooling. Int J Microcirc Clin Exp. 1997 Apr;17(2):55–60. doi: 10.1159/000179207 9253681

42. Venjakob AJ, Vogt S, Stöckl K, Tischer T, Jost PJ, Thein E, et al. Local cooling reduces regional bone blood flow. J Orthop Res Off Publ Orthop Res Soc. 2013 Nov;31(11):1820–7.

43. Mustafa S, Thulesius O. Cooling-induced carotid artery dilatation: an experimental study in isolated vessels. Stroke. 2002 Jan;33(1):256–60. doi: 10.1161/hs0102.101545 11779919

44. Kalia N, Pockley AG, Wood RFM, Brown NJ. Effects of hypothermia and rewarming on the mucosal villus microcirculation and survival after rat intestinal ischemia-reperfusion injury. Ann Surg. 2002 Jul;236(1):67–74. doi: 10.1097/00000658-200207000-00011 12131087

45. Clark DL, Colbourne F. A simple method to induce focal brain hypothermia in rats. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2007 Jan;27(1):115–22.

46. Polderman KH, Herold I. Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med. 2009 Mar;37(3):1101–20. doi: 10.1097/CCM.0b013e3181962ad5 19237924

47. Han Y-S, Tveita T, Prakash YS, Sieck GC. Mechanisms underlying hypothermia-induced cardiac contractile dysfunction. Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H890–897. doi: 10.1152/ajpheart.00805.2009 20023122

48. Umehara S, Tanaka M, Nishikawa T. Effects of sevoflurane anesthesia on carotid-cardiac baroreflex responses in humans. Anesth Analg. 2006 Jan;102(1):38–44. doi: 10.1213/01.ane.0000183651.10514.9a 16368802

49. Wangensteen SL, Barker HG, Smith RB, Flood CA, Berakha GJ. GASTRIC “FREEZING”: AN INITIAL CLINICAL STUDY. Am J Med. 1965 Jan;38:31–41. doi: 10.1016/0002-9343(65)90157-9 14247289

50. Johansson T, Lisander B, Ivarsson I. Mild hypothermia does not increase blood loss during total hip arthroplasty. Acta Anaesthesiol Scand. 1999 Nov;43(10):1005–10. doi: 10.1034/j.1399-6576.1999.431006.x 10593462

51. Rajagopalan S, Mascha E, Na J, Sessler DI. The effects of mild perioperative hypothermia on blood loss and transfusion requirement. Anesthesiology. 2008 Jan;108(1):71–7. doi: 10.1097/01.anes.0000296719.73450.52 18156884

52. Sheridan WG, Lowndes RH, Young HL. Tissue oxygen tension as a predictor of colonic anastomotic healing. Dis Colon Rectum. 1987 Nov;30(11):867–71. doi: 10.1007/bf02555426 3677962

Článek vyšel v časopise


2019 Číslo 12
Nejčtenější tento týden