title: Resistance to systemic inflammation and multi organ damage after global ischemia/reperfusion in the arctic ground squirrel.
abstract: BACKGROUND
  Cardiac arrest (CA) and hemorrhagic shock (HS) are two clinically relevant situations where the body undergoes global ischemia as blood pressure drops below the threshold necessary for adequate organ perfusion. Resistance to ischemia/reperfusion (I/R) injury is a characteristic of hibernating mammals. The present study sought to determine if arctic ground squirrels (AGS) are protected from systemic inflammation and multi organ damage after CA- or HS-induced global I/R and if, for HS, this protection is dependent upon their hibernation season.
  
  
  METHODS
  For CA, rats and summer euthermic AGS (AGS-EU) were asphyxiated for 8 min, inducing CA. For HS, rats, AGS-EU, and winter interbout arousal AGS (AGS-IBA) were subject to HS by withdrawing blood to a mean arterial pressure of 35 mmHg and maintaining that pressure for 20 min before reperfusion with Ringers. For both I/R models, body temperature (Tb) was kept at 36.5-37.5°C. After reperfusion, animals were monitored for seven days (CA) or 3 hrs (HS) then tissues and blood were collected for histopathology, clinical chemistries, and cytokine level analysis (HS only). For the HS studies, additional groups of rats and AGS were monitored for three days after HS to access survival and physiological impairment.
  
  
  RESULTS
  Rats had increased serum markers of liver damage one hour after CA while AGS did not. For HS, AGS survived 72 hours after I/R whereas rats did not survive overnight. Additionally, only rats displayed an inflammatory response after HS. AGS maintained a positive base excess, whereas the base excess in rats was negative during and after hemorrhage.
  
  
  CONCLUSIONS
  Regardless of season, AGS are resistant to organ damage, systemic inflammation, and multi organ damage after systemic I/R and this resistance is not dependent on their ability to become decrease Tb during insult but may stem from an altered acid/base and metabolic response during I/R.
authors.affiliation: Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, Alaska, United States of America; Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska, United States of America.
authors.forename: Lori K
authors.initials: LK
authors.lastname: Bogren
authors.affiliation: Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, Alaska, United States of America.
authors.forename: Jasmine M
authors.initials: JM
authors.lastname: Olson
authors.affiliation: Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, Alaska, United States of America.
authors.forename: Joanna
authors.initials: J
authors.lastname: Carpluk
authors.affiliation: Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska, United States of America.
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: Moore
authors.affiliation: Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, Alaska, United States of America; Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska, United States of America.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Drew
mesh_terms: D000818:Animals; D005260:Female; D007249:Inflammation / Q000503:physiopathology* / Q000517:prevention & control*; D008297:Male; D009102:Multiple Organ Failure / Q000503:physiopathology* / Q000517:prevention & control*; D051381:Rats; D015427:Reperfusion Injury / Q000503:physiopathology*; D012589:Sciuridae
references.citation: Science. 1989 Jun 30;244(4912):1593-5
references.pmid: 2740905
references.citation: Nat Med. 2011 Nov 07;17(11):1391-401
references.pmid: 22064429
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Feb;296(2):R383-93
references.pmid: 19052316
references.citation: Transplantation. 2011 Dec 15;92(11):1215-21
references.pmid: 22082817
references.citation: Am J Physiol Regul Integr Comp Physiol. 2005 Nov;289(5):R1297-306
references.pmid: 15976308
references.citation: Neurosci Lett. 2006 Aug 14;404(1-2):170-5
references.pmid: 16781056
references.citation: Epilepsia. 2002 Nov;43(11):1360-71
references.pmid: 12423386
references.citation: Surgeon. 2012 Dec;10(6):350-6
references.pmid: 22534256
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Jul;295(1):R316-28
references.pmid: 18434441
references.citation: Curr Pharm Des. 2012;18(37):6053-69
references.pmid: 22747536
references.citation: Am J Cardiovasc Dis. 2012;2(3):237-47
references.pmid: 22937493
references.citation: J Emerg Med. 2003 May;24(4):413-22
references.pmid: 12745044
references.citation: Science. 1996 Nov 22;274(5291):1383-5
references.pmid: 8910280
references.citation: J Exp Biol. 2011 Apr 15;214(Pt 8):1300-6
references.pmid: 21430207
references.citation: J Cereb Blood Flow Metab. 2003 Jul;23(7):865-77
references.pmid: 12843790
references.citation: Am J Physiol Regul Integr Comp Physiol. 2001 Aug;281(2):R572-83
references.pmid: 11448862
references.citation: Am J Physiol Gastrointest Liver Physiol. 2010 Oct;299(4):G833-43
references.pmid: 20689059
references.citation: Adv Exp Med Biol. 2003;521:148-60
references.pmid: 12617572
references.citation: Injury. 2009 Sep;40(9):912-8
references.pmid: 19541301
references.citation: Inflamm Res. 1996 Jun;45(6):299-302
references.pmid: 8814462
references.citation: Crit Care. 2005 Oct 5;9(5):441-53
references.pmid: 16277731
references.citation: J Neurochem. 2005 Jun;93(5):1327-33
references.pmid: 15934951
references.citation: Am J Physiol Gastrointest Liver Physiol. 2006 Nov;291(5):G895-901
references.pmid: 16751173
references.citation: J Cereb Blood Flow Metab. 2008 Jul;28(7):1307-19
references.pmid: 18398417
references.citation: Mediators Inflamm. 2010;2010:642462
references.pmid: 20628562
references.citation: Crit Care. 2008;12(4):218
references.pmid: 18638356
references.citation: Microsurgery. 2004;24(3):223-31
references.pmid: 15160382
references.citation: Eur J Pharmacol. 2002 Oct 25;453(2-3):189-95
references.pmid: 12398903
references.citation: Biol Lett. 2012 Feb 23;8(1):31-4
references.pmid: 21752811
references.citation: Ann Intensive Care. 2011 Nov 03;1(1):45
references.pmid: 22053891
references.citation: J Cereb Blood Flow Metab. 2006 Sep;26(9):1148-56
references.pmid: 16395285
references.citation: Crit Care. 2004 Oct;8(5):373-81
references.pmid: 15469601
references.citation: JNMA J Nepal Med Assoc. 2008 Apr-Jun;47(170):82-5
references.pmid: 18709037
references.citation: J Neurochem. 2009 Aug;110(4):1170-9
references.pmid: 19493168
references.citation: Am J Physiol Gastrointest Liver Physiol. 2005 Mar;288(3):G473-80
references.pmid: 15701622
references.citation: J Infect Dis. 1998 May;177(5):1418-21
references.pmid: 9593038
references.citation: Neuropharmacology. 1993 Oct;32(10):1047-59
references.pmid: 8295713
references.citation: Neurosci Res. 2003 Oct;47(2):245-53
references.pmid: 14512150
references.citation: Injury. 2010 Jan;41(1):21-6
references.pmid: 19729158
references.citation: Circulation. 2010 Nov 2;122(18 Suppl 3):S768-86
references.pmid: 20956225
references.citation: Shock. 2010 Dec;34(6):565-72
references.pmid: 20386494
references.citation: Curr Opin Crit Care. 2001 Dec;7(6):437-43
references.pmid: 11805547
references.citation: Stroke. 2006 May;37(5):1261-5
references.pmid: 16574920
references.citation: J Cereb Blood Flow Metab. 1998 Feb;18(2):168-75
references.pmid: 9469159