Document Detail


Novel model of peripheral tissue trauma-induced inflammation and gastrointestinal dysmotility.
MedLine Citation:
PMID:  21303433     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Trauma is a leading cause of death and although the gut is recognized as the 'motor' of post-traumatic systemic inflammatory response syndrome and multiple organ failure, studies on the gastrointestinal (GI) tract are few. Our objectives were to create a precisely controllable tissue injury model in which GI motility, systemic inflammation and wound fluid can be analyzed.
METHODS: A non-narcotic murine trauma model was developed by the subcutaneous dorsal trans-implantation of a devitalized donor syngeneic harvested tissue-bone matrix (TBX), which was precisely adjusted to % total body weight and studied after 21 h. Gastrointestinal transit histograms were plotted after the oral administration of non-digestible FITC-dextran and geometric centers calculated. Organ bath evaluated jejunal circular muscle contractility. Multiplex electrochemiluminescence measurements of serum and TBX wound fluid inflammatory mediators were performed.
KEY RESULTS: Increasing TBX amounts progressively delayed transit, whereas TBX heat denaturation or decellularization prevented ileus and death. In the TBX(17.5%) model, jejunal muscle contractility was suppressed and a systemic inflammatory response developed as significant serum elevations in IL-6, keratinocyte cytokine and IL-10 compared to sham. In addition, inflammatory responses within the wound fluid showed elevated levels of preformed IL-1β and TNF-α, whereas, 21 h after implantation IL-1β, IL-6 and keratinocyte cytokine were significantly increased in the wound.
CONCLUSIONS & INFERENCES: A novel donor tissue-bone matrix trauma model was developed that is precisely adjustable and recapitulates important clinical phenomena. The non-narcotic model demonstrated that increasing tissue injury progressively caused ileus, initiated a systemic inflammatory response and developed inflammatory changes within the wound.
Authors:
T Tsukamoto; V Antonic; I I El Hajj; A Stojadinovic; D G Binion; M J Izadjoo; H Yokota; H C Pape; A J Bauer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-09
Journal Detail:
Title:  Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society     Volume:  23     ISSN:  1365-2982     ISO Abbreviation:  Neurogastroenterol. Motil.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-05-31     Completed Date:  2011-10-11     Revised Date:  2012-04-04    
Medline Journal Info:
Nlm Unique ID:  9432572     Medline TA:  Neurogastroenterol Motil     Country:  England    
Other Details:
Languages:  eng     Pagination:  379-86, e164     Citation Subset:  IM    
Copyright Information:
© 2011 Blackwell Publishing Ltd.
Affiliation:
Department of Medicine/Gastroenterology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Matrix / transplantation
Gastrointestinal Diseases / blood,  etiology*,  physiopathology
Gastrointestinal Motility / physiology*
Inflammation / blood,  etiology*,  physiopathology
Interleukin-10 / blood
Interleukin-1beta / blood
Interleukin-6 / blood
Male
Mice
Mice, Inbred C57BL
Models, Animal*
Muscle Contraction / physiology
Systemic Inflammatory Response Syndrome / blood,  etiology*,  physiopathology
Tumor Necrosis Factor-alpha / blood
Wounds and Injuries / complications*
Grant Support
ID/Acronym/Agency:
DK02488/DK/NIDDK NIH HHS; P50-GM-53789/GM/NIGMS NIH HHS; R01 DK068610-05/DK/NIDDK NIH HHS; R01 GM058241-05/GM/NIGMS NIH HHS; R01 GM058241-09/GM/NIGMS NIH HHS; R01-DK068610/DK/NIDDK NIH HHS; R01-GM58241/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-1beta; 0/Interleukin-6; 0/Tumor Necrosis Factor-alpha; 130068-27-8/Interleukin-10

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