Altered migrating myoelectrical complex in an animal model of cholesterol gallstone disease: the effect of erythromycin.
BACKGROUND
The ground squirrel on a high cholesterol diet exhibits prolonged intestinal transit, a pathogenetic factor in cholesterol gallstone formation.


OBJECTIVE
To examine the effect of a high cholesterol diet on the characteristics of the migrating myoelectrical complex (MMC) and the potential benefit of erythromycin.


METHODS
Twenty four animals received either a trace (controls) or a 1% (high) cholesterol diet. After four weeks, five bipolar jejunal and terminal ileal electrodes were implanted. Seven days later, myoelectric activity was measured in conscious, fasted animals before and after treatment with erythromycin. Biliary lipid composition was assessed.


RESULTS
Compared with controls, animals fed the high cholesterol diet exhibited a prolonged MMC cycle period (70 (6) versus 83 (3) minutes; p<0.05), whereas MMC migration velocity and the proportions of the MMC represented by phases I, II, and III were unchanged. Oral erythromycin significantly shortened the MMC cycle period in animals on the control and high cholesterol diet by 59% and 54% respectively, and increased the proportion of the cycle period occupied by phase III of the MMC in both dietary groups. Gall bladder bile became saturated with cholesterol and crystals developed in nine of 12 animals on the high cholesterol diet; controls had none.


CONCLUSIONS
Animals fed a high cholesterol diet had a prolonged MMC cycle period. This, along with diminished gall bladder motility, impairs the enterohepatic cycling of bile salts and reduces their hepatic secretion, contributing to the formation of abnormal bile. Erythromycin initiated more frequent cycling of the MMC. Its therapeutic value in cholesterol gallstone formation warrants further evaluation.
Xu
Q W
QW
GI Research Group, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Scott
R B
RB
Tan
D T
DT
Shaffer
E A
EA
D000818:Animals; D001646:Bile / Q000737:chemistry*; D002769:Cholelithiasis / Q000737:chemistry* / Q000209:etiology; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004917:Erythromycin / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D007422:Intestines / Q000502:physiology*; D050356:Lipid Metabolism; D016065:Myoelectric Complex, Migrating / Q000187:drug effects / Q000502:physiology*; D012589:Sciuridae
D002791:Cholesterol, Dietary; D005765:Gastrointestinal Agents; D004917:Erythromycin