Ischemia/reperfusion: a clinically relevant model of intestinal injury yielding systemic inflammation.
OBJECTIVE
Multisystem organ failure (MSOF) is a major cause of morbidity and mortality in the critically ill patient. Animal models of endotoxin-induced sepsis were used to develop therapeutic regimens, which thus far have failed in clinical trials. Because multiple etiologies of MSOF affect the intestine, the authors hypothesized that during sepsis the gut may act as a possible trigger of the inflammatory cascade. As ischemia and reperfusion of the small intestine disrupts gut barrier function, thereby activating systemic inflammatory responses, the authors evaluated a murine model of ischemia/reperfusion to investigate these systemic responses to local mucosal and epithelial injury.


METHODS
C57BL/10 and Balb/c mice underwent variable amounts of gut ischemia by superior mesenteric artery occlusion. Animals were evaluated for survival as well as gross and microscopic intestinal damage.


RESULTS
Maximal ischemic damage occurred in the distal jejunum and proximal ileum. More severe epithelial damage and transmural inflammation were observed in C57BL/10 mice, which correlated with a higher mortality.


CONCLUSIONS
This model mimics what is observed clinically with intestinal injury resulting from a progressive ischemic insult with eventual systemic manifestations. This reproducible model of systemic inflammation elicits variable responses from genetically different animals, the results of which may lead to a better understanding of MSOF.
Stallion
Anthony
A
Department of Pediatric Surgery, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4952, USA.
Kou
Tzuyung D
TD
Latifi
Samir Q
SQ
Miller
Kelly A
KA
Dahms
Beverly B
BB
Dudgeon
David L
DL
Levine
Alan D
AD
D000818:Animals; D003250:Constriction; D016207:Cytokines / Q000502:physiology*; D004195:Disease Models, Animal; D007082:Ileum / Q000098:blood supply / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply* / Q000473:pathology; D007511:Ischemia / Q000473:pathology*; D007583:Jejunum / Q000098:blood supply / Q000473:pathology; D017538:Mesenteric Artery, Superior; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000209:etiology* / Q000473:pathology; D015427:Reperfusion Injury / Q000473:pathology*; D013047:Specific Pathogen-Free Organisms; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology* / Q000473:pathology
D016207:Cytokines