Sepsis-induced organ failure is associated with high morbidity and mortality
rates. The onset of an exaggerated host response to microbial invasion and/or trauma, is believed to be the primary cause of excessive inflammation and the subsequent tissue hypoperfusion observed in patients with severe sepsis. In our mouse model of sepsis induced by cecal ligation and perforation (CLP), symptoms indicative of the disease, including diarrhea, increased ventilation and persistent hypothermia, are present at six hours after the surgery (T6). In the untreated CLP mice, mortality occurs starting at T15. As induced hypothermia has shown to exert immunomodulatory effects, this study is aimed at assessing its potential in attenuating inflammation and improving survival in experimental sepsis. Our data has shown that deep hypothermia initiated at T6, by means of cold chamber-induced cooling, prolongs survival. Plasma cytokine quantification by enzyme-linked immunosorbent assays (ELISA) also reveals that induced deep hypothermia reduces tumour necrosis factor(TNF)-α and interleukin (IL)-6 production in untreated CLP mice. In contrast, induced moderate hypothermia does not have such effect. Antibiotic (cefotaxime) and saline resuscitation initiated immediately following CLP ensures survival. However, when these supportive treatments are initiated at T6, >50% mortality is observed in the CLP mice with or without induced hypothermia. In summary, this preliminary study provides proof for a downregulated inflammatory response mediated by external cooling. However, to achieve a survival benefit, treatment strategies in addition to cooling and antibiotics may be required.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OOU./en#10393/20119 |
| Date | 25 July 2011 |
| Creators | Luo, Karen Yao |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thèse / Thesis |
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