EFFECT OF THE PROKINETIC AGENT, ERYTHROMYCIN, IN THE RICHARDSON GROUND-SQUIRREL MODEL OF CHOLESTEROL GALLSTONE DISEASE

Impaired gallbladder motility and delayed intestinal transit contribut e to cholesterol gallstone formation by impeding the enterohepatic cir culation of bile salts and causing gallbladder stasis, The therapeutic value of erythromycin, a prokinetic motilin analog, was evaluated in an animal model of gallstone formation. Eighty ground squirrels were f ed either a trace- (control) or a high- (1%) cholesterol diet. Half of each diet group received either erythromycin stearate or placebo oral ly twice daily for 4 weeks. Biliary lipid secretion and bile salt pool size were determined via common duct cannulation, Gallbladder contrac tile response to cholecystokinin (CCK) was studied in vitro, Intestina l transit was evaluated in vivo by Cr-51 marker, In the placebo-treate d group, fed the high- versus the trace-cholesterol diet, bile salt se cretion decreased (trace-cholesterol + placebo, 21.0 +/- 1.8 nmol/min/ g liver vs, high-cholesterol + placebo, 9.3 +/- 1.4 nmol/min/g liver), cholesterol saturation index (CSI) doubled (trace-cholesterol + place bo, 0.61 +/- 0.06 vs. high-cholesterol +/- placebo, 1.30 +/- 0.04), nu cleation time shortened (trace-cholesterol + placebo, >21 days vs. hig h-cholesterol + placebo, 6.4 +/- 1.0 days), cholesterol crystals forme d, gallbladder contractility diminished, and intestinal transit was de layed (each P < .05), Erythromycin treatment of animals on the high-ch olesterol diet restored gallbladder contractility and intestinal trans it to control levels, increased bile salt secretion, reduced the total bile salt pool, lowered the cholesterol saturation of bile, lengthene d the nucleation time, and so reduced crystal formation (each P < .05) . Erythromycin enhances gallbladder motility and hastens intestinal tr ansit, promoting more rapid enterohepatic cycling of bile salts. This increases bile salt secretion, improves cholesterol solubility, and re duces crystal development.