Gradual development of organ damage in the murine zymosan-induced multiple organ dysfunction syndrome.
A well defined animal model is a prerequisite to test intervention strategies aimed at preventing the development of the multiple organ dysfunction syndrome. This study compares changes in clinical parameters to histopathologic changes in tissues, observed over a 12 day period after a single intraperitoneal injection of zymosan in C57BL/6 mice. Administration of zymosan induced gradual and progressive changes in wet and dry organ weight of the liver, kidneys, and particularly, lungs and spleen that correlated with increasing histopathology. From 6 days after zymosan injection onwards, hemorrhagic spots were found in the lungs evolving into massive hemorrhages at 12 days, when thickened interstitial walls and loss of the honey comb-like structures were observed. The liver displayed progressive accumulation of macrophage-like and mononuclear cells. After 12 days, numerous granuloma-like structures were disseminated throughout the liver parenchyma. The spleen displayed great changes in red and white pulp with increasing numbers of megakaryocytes and plasma-like cells. In the kidneys, necrosis of the tubular epithelium adjacent to granulomas on the ventral (peritoneal) side was found. In mice, a single intraperitoneal challenge with zymosan leads to progressive multiple organ damage, which becomes apparent at some time after the insult. This animal model displays a number of features encountered in human multiple organ dysfunction syndrome and appears suitable to conduct intervention studies.
Jansen
M J
MJ
Department of Surgery, University Hospital Nijmegen, The Netherlands.
Hendriks
T
T
Verhofstad
A A
AA
Lange
W
W
Geeraedts
L M
LM
Goris
R J
RJ
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D015996:Survival Rate; D013997:Time Factors; D015054:Zymosan / Q000633:toxicity*
D015054:Zymosan