A conscious mouse model of gastric ileus using clinically relevant endpoints.
BACKGROUND
Gastric ileus is an unsolved clinical problem and current treatment is limited to supportive measures. Models of ileus using anesthetized animals, muscle strips or isolated smooth muscle cells do not adequately reproduce the clinical situation. Thus, previous studies using these techniques have not led to a clear understanding of the pathophysiology of ileus. The feasibility of using food intake and fecal output as simple, clinically relevant endpoints for monitoring ileus in a conscious mouse model was evaluated by assessing the severity and time course of various insults known to cause ileus.


METHODS
Delayed food intake and fecal output associated with ileus was monitored after intraperitoneal injection of endotoxin, laparotomy with bowel manipulation, thermal injury or cerulein induced acute pancreatitis. The correlation of decreased food intake after endotoxin injection with gastric ileus was validated by measuring gastric emptying. The effect of endotoxin on general activity level and feeding behavior was also determined. Small bowel transit was measured using a phenol red marker.


RESULTS
Each insult resulted in a transient and comparable decrease in food intake and fecal output consistent with the clinical picture of ileus. The endpoints were highly sensitive to small changes in low doses of endotoxin, the extent of bowel manipulation, and cerulein dose. The delay in food intake directly correlated with delayed gastric emptying. Changes in general activity and feeding behavior were insufficient to explain decreased food intake. Intestinal transit remained unchanged at the times measured.


CONCLUSIONS
Food intake and fecal output are sensitive markers of gastric dysfunction in four experimental models of ileus. In the mouse, delayed gastric emptying appears to be the major cause of the anorexic effect associated with ileus. Gastric dysfunction is more important than small bowel dysfunction in this model. Recovery of stomach function appears to be simultaneous to colonic recovery.
Firpo
Matthew A
MA
Department of Surgery, University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT 84132, USA. matt.firpo@hsc.utah.edu
Rollins
Michael D
MD
Szabo
Aniko
A
Gull
Justin D
JD
Jackson
Jeffrey D
JD
Shao
Yuanlin
Y
Glasgow
Robert E
RE
Mulvihill
Sean J
SJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D003672:Defecation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004731:Endotoxins / Q000008:administration & dosage; D005746:Gastric Emptying / Q000187:drug effects; D017219:Gastric Outlet Obstruction / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology*; D005772:Gastrointestinal Transit / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009043:Motor Activity / Q000187:drug effects; D013997:Time Factors
D004731:Endotoxins; D008070:Lipopolysaccharides