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Experimental diet-induced dog gallstones contained mainly protein, mucous substances, bile salts, bilirubin, an insoluble pigment which formed an insoluble black residue after acid hydrolysis, and only traces of cholesterol. Added dietary cholesterol was necessary to pigmented gallstone production and led to hypercholesterolemia. In bile, the ratio of cholesterol to bile salts was increased, but phospholipids were increased and cholesterol insolubility was not found. Dry weight, osmolality, and concentration of sodium and potassium in bile were reduced, but were not considered sufficient to influence micelle formation or lipid-pigment solubility. Taurine was reduced in serum and bile and unconjugated bile acids appeared in gallbladder bile; the pKa of these acids is near the pH of bile in these animals and may have caused precipitation of bile acids, accounting for their presence in the stones. Bile cultures were sterile. Total bilirubin content was unaltered but the methods used did not exclude the presence of unconjugated bilirubin as a potential cause of pigment precipitation in aqueous bile. Increased numbers of secretory vesicles occurred in gallbladder epithelium and large amounts of mucus were in the epithelial crypts. These observations suggest that bile proteins or mucous substances are important to lithogenesis in this model.

EXPERIMENTAL models of gallstone formation have been described in many species1,2, but the lithogenic methods used were unphysiological or unnatural. In dogs, spontaneous gallstones are rare1, and human cholesterol gallstones placed in the dog gallbladder will dissolve3. Canine gallstones occur in biliary fistulas4, but the only report of gallbladder stones followed combined cholesterol-feeding and occlusion of the cystic duct5. To induce stones physiologically in this resistant species, we designed a diet in 1965 which hypothetically would alter bile salt–phospholipid–cholesterol–pigment relationships in bile and cause bile stasis as follows: low amounts of protein, high content of sugar and no added bile salts to reduce total bile salt and volume-flow of bile6,7; low content of total and unsaturated fat to reduce and alter phospho-lipids and bile salts in bile and to decrease gallbladder contractions8–10; and added cholesterol to overcome the cholesterol-holding capacity of dog bile1,11. Cornstarch and multiple small feedings were added further to simulate diets of certain human populations with a high incidence of cholelithiasis, for example, the Pima Indians12, or produce biliary stasis1,8. The diet was compounded of purified casein 10 per cent, sucrose 50 per cent, cornstarch 26 per cent, animal lard 5 per cent, cholesterol USP 1 per cent, salt mixture USP XIV 5 per cent, ‘Vitamin Diet Fortification Mixture’ 2 per cent and cellulose as filler 1 per cent (Nutritional Biochemicals Corporation, Cleveland, Ohio).