title: Interaction of hemorrhagic shock and subsequent polymicrobial sepsis on gastrointestinal motility.
abstract: Understanding "two-hit" experimental models is crucial for the rational development of therapies for hemorrhagic shock (HS). We modeled the clinical scenario of HS followed by polymicrobial sepsis (cecal ligation and puncture [CLP]) to investigate the molecular and functional alterations that occur within the gastrointestinal tract. Control, HS, CLP, simultaneous HS + CLP, and HS + delayed CLP by 24 h groups of Sprague-Dawley rats were studied for gastrointestinal transit and in vitro colonic circular muscle contractility to bethanechol. Reverse transcription-polymerase chain reaction quantified IL-6, IL-10, and heme oxygenase 1 messenger RNA expression in the isolated colonic muscularis 6 h after insult. Myeloperoxidase-positive neutrophils were quantified in colonic muscularis whole mounts. Mortality at 24 h was significantly increased in simultaneous mild HS + CLP (88%) over control, mild HS, CLP alone, or HS + delayed CLP. Cecal ligation and puncture significantly delayed transit compared with controls and HS alone. Hemorrhagic shock + delayed CLP animals had normal transit. Colonic contractions were suppressed by 50% after CLP compared with controls and HS. In contrast, HS + delayed CLP displayed control levels of contractile responses to bethanechol. Cecal ligation and puncture and simultaneous HS + CLP caused significant inflammatory messenger RNA induction of IL-6, iNOS, IL-10, and heme oxygenase 1 compared with control and HS, and these responses were significantly suppressed in HS + delayed CLP colonic muscularis extracts. Neutrophils were significantly recruited into the colonic muscularis following CLP after 24 h compared with control and HS. This recruitment was significantly less in the HS + delayed CLP animals. These data demonstrate the ability of mild HS to precondition the animal and protect it against a delayed, but not simultaneous, polymicrobial event.
authors.affiliation: Department of Medicine/Gastroenterology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Overhaus
authors.forename: Sandra
authors.initials: S
authors.lastname: Toegel
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bauer
mesh_terms: D000818:Animals; D001794:Blood Pressure; D003106:Colon / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005769:Gastrointestinal Motility / Q000502:physiology*; D005772:Gastrointestinal Transit / Q000502:physiology; D007962:Leukocytes / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D018805:Sepsis / Q000209:etiology* / Q000382:microbiology* / Q000503:physiopathology; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000503:physiopathology*
references.citation: Surgery. 2000 Aug;128(2):332-8
references.pmid: 10923013
references.citation: Surg Clin North Am. 1995 Apr;75(2):257-77
references.pmid: 7899997
references.citation: Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G695-703
references.pmid: 16537973
references.citation: Shock. 2003 Apr;19(4):358-65
references.pmid: 12688548
references.citation: J Trauma. 2003 Jul;55(1):118-25
references.pmid: 12855890
references.citation: Ann Surg. 1993 Aug;218(2):111-9
references.pmid: 8342990
references.citation: Cytokine. 2005 Aug 7;31(3):169-79
references.pmid: 15961314
references.citation: Shock. 2005 Mar;23(3):258-63
references.pmid: 15718925
references.citation: Gastroenterology. 2002 Aug;123(2):586-98
references.pmid: 12145811
references.citation: J Exp Med. 1995 May 1;181(5):1887-92
references.pmid: 7722463
references.citation: Circulation. 1986 Nov;74(5):1124-36
references.pmid: 3769170
references.citation: Am J Physiol Gastrointest Liver Physiol. 2004 Feb;286(2):G225-33
references.pmid: 14715517
references.citation: Anal Biochem. 2000 Oct 15;285(2):194-204
references.pmid: 11017702
references.citation: J Immunol. 1999 Jan 1;162(1):392-9
references.pmid: 9886412
references.citation: Am J Physiol. 1999 Aug;277(2):G478-86
references.pmid: 10444463
references.citation: Langenbecks Arch Surg. 2002 Jan;386(7):512-7
references.pmid: 11819109
references.citation: Arch Surg. 2001 Nov;136(11):1263-6
references.pmid: 11695970
references.citation: Dig Dis Sci. 2001 Feb;46(2):230-41
references.pmid: 11281168
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10393-8
references.pmid: 8816811
references.citation: J Pharmacol Exp Ther. 1997 Feb;280(2):656-63
references.pmid: 9023276
references.citation: Langenbecks Arch Surg. 2001 Jul;386(4):302-8
references.pmid: 11466573
references.citation: Am J Pathol. 2002 Dec;161(6):2283-94
references.pmid: 12466142
references.citation: New Horiz. 1996 May;4(2):289-99
references.pmid: 8774803
references.citation: Surgery. 1999 Mar;125(3):339-44
references.pmid: 10076620
references.citation: Gastroenterology. 2000 Feb;118(2):316-27
references.pmid: 10648460
references.citation: Surgery. 1999 Sep;126(3):498-509
references.pmid: 10486602
references.citation: J Immunol. 1998 Dec 1;161(11):6288-96
references.pmid: 9834118
references.citation: Curr Opin Crit Care. 2003 Apr;9(2):143-51
references.pmid: 12657978
references.citation: J Trauma. 1998 May;44(5):750-8; discussion 758-9
references.pmid: 9603074
references.citation: Am J Physiol Gastrointest Liver Physiol. 2004 Apr;286(4):G580-7
references.pmid: 15010362
references.citation: Shock. 2005 Dec;24 Suppl 1:71-4
references.pmid: 16374376
references.citation: Burns. 2003 Feb;29(1):1-14
references.pmid: 12543039
references.citation: Am J Physiol Gastrointest Liver Physiol. 2002 Aug;283(2):G408-14
references.pmid: 12121889
references.citation: Ann Surg. 1992 Apr;215(4):356-62
references.pmid: 1558416
references.citation: Crit Care Med. 1996 Jul;24(7):1125-8
references.pmid: 8674323
references.citation: Br J Surg. 2005 Sep;92(9):1169-76
references.pmid: 16044427
references.citation: Transplantation. 1999 Nov 15;68(9):1244-54
references.pmid: 10573059
references.citation: Am J Physiol Gastrointest Liver Physiol. 2003 Apr;284(4):G713-21
references.pmid: 12466147
references.citation: Am J Physiol Gastrointest Liver Physiol. 2004 Sep;287(3):G685-94
references.pmid: 15331356
references.citation: Am J Physiol Gastrointest Liver Physiol. 2002 Jan;282(1):G145-55
references.pmid: 11751168
references.citation: Ann Surg. 1998 Nov;228(5):652-63
references.pmid: 9833803
references.citation: Arch Orthop Trauma Surg. 1999;119(1-2):89-93
references.pmid: 10076954
references.citation: Am J Physiol. 1997 Nov;273(5):L1058-64
references.pmid: 9374735
references.citation: Am J Physiol. 1999 Jun;276(6):G1356-62
references.pmid: 10362638
references.citation: Am J Physiol. 1997 Sep;273(3 Pt 1):G727-34
references.pmid: 9316478
references.citation: J Immunol. 2006 Aug 1;177(3):1967-74
references.pmid: 16849510
references.citation: Int J Mol Med. 1999 Dec;4(6):575-83
references.pmid: 10567665
references.citation: J Trauma. 2003 Aug;55(2):298-307
references.pmid: 12913641
references.citation: J Trauma. 1996 Apr;40(4):501-10; discussion 510-2
references.pmid: 8614027
references.citation: J Vasc Surg. 2003 Nov;38(5):1113-20
references.pmid: 14603224
references.citation: Ann Surg. 1999 Apr;229(4):478-86
references.pmid: 10203079
references.citation: Gastroenterology. 1993 Feb;104(2):398-409
references.pmid: 8425682
references.citation: Crit Care Med. 2002 Jan;30(1 Supp):S58-S63
references.pmid: 11839946
references.citation: J Surg Res. 1996 Feb 1;60(2):307-11
references.pmid: 8598659
references.citation: Trends Immunol. 2003 Aug;24(8):449-55
references.pmid: 12909459