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AJW Samis, S Vanner, W Paterson, G Morris

Gastrointestinal Diseases Research Unit, Queen’s University, Kingston, Ontario

Sepsis-induced gastric dysmotility prevents optimum nutrition in the ICU and leads to increased morbidity and mortality. The mechanisms which underlie these motility changes however are unclear. The objective of this study to establish an in vivo model of sepsis-induced gastric dysmotility in the mouse as a first step towards understanding the cellular mechanisms involved.

METHODS: Mice (CD1, weight 20-30 g) were fasted for 6 hours and then allowed to eat liberally for 30 minutes. Following the 30-minute feeding period the mice were injected parenterally with endotoxin (Lipopolysaccharide from Escherichia coli Serotype 0111:B4) at doses of 0 (control), 30 and 100 mg/kg. The mice were then fasted for an additional 6 hours, at which point their activity level, degree of piloerection, respiratory rate, and body temperature were recorded by a blinded observer. They were then euthanized for gastric content removal. The dry weight of gastric content was compared with dry weight of food consumed as a measure of gastric motility during the 6 hours post-injection. The dry weight of stomach contents are expressed as a percent of the dry weight of food consumed.

RESULTS: After the initial six hour fast, mice had less than 5 mg (dry weight) of gastric contents. After feeding liberally for 30 minutes, the mice consumed a mean of 134±23 mg (dry weight ± SE) of food, with no significant differences between groups destined to receive the different doses of endotoxin. At six hours the mice receiving endotoxin were less active, had a greater degree of piloerection, and had increased respiratory rate and body temperature indicating a systemic effect. The dry weight of the gastric contents expressed as a percentage of dry weight of food consumed 6 hours before was 11.1% for mice injected with 0 mg/kg of endotoxin 31.0% for mice injected with 30 mg/kg, and 49.8% for mice injected with 100 mg/kg (p<0.0001).

CONCLUSIONS: Parenteral administration of endotoxin produced a dose-dependent gastric dysmotility and correlated with clinical signs of sepsis. This validated mouse model will enable the study of gene-targeted deletions in in vitro studies to identify the cellular mechanism(s) involved.

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