Interaction of hemorrhagic shock and subsequent polymicrobial sepsis on gastrointestinal motility.
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.
Overhaus
Marcus
M
Department of Medicine/Gastroenterology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Toegel
Sandra
S
Bauer
Anthony J
AJ
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*
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