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Neurogastroenterol Motil. 2011 Apr;23(4):379-86, e164. doi: 10.1111/j.1365-2982.2011.01675.x. Epub 2011 Feb 9.

Novel model of peripheral tissue trauma-induced inflammation and gastrointestinal dysmotility.

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  • 1Department of Medicine/Gastroenterology, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Abstract

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.

PMID:
21303433
PMCID:
PMC3105173
DOI:
10.1111/j.1365-2982.2011.01675.x
[PubMed - indexed for MEDLINE]
Free PMC Article
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