Effect of dietary ethanol on gallbladder absorption and cholesterol gallstone formation in the prairie dog

Dietary ethanol has been reported to protect against cholesterol gallstone formation. Because enhanced gallbladder absorption of water is important in cholesterol cholelithiasis, we examined the hypothesis that ethanol acts by inhibiting the absorptive function of the gallbladder. Eighteen adult male prairie dogs were fed a lithogenic liquid diet containing 0.4% cholesterol. Half of the animals received 30% of total calories as ethanol, whereas their pair-fed controls received equicaloric amounts of maltose-dextrin. After 3 months, the gallbladders were inspected for gallstones and crystals, and gallbladder and hepatic bile were analyzed. Cholesterol stones and crystals were present in all nine controls. None of the alcohol-fed animals had stones, but four had cholesterol crystals. Gallbladder cholesterol, phospholipids, and total calcium were significantly decreased in alcohol-fed animals. In both gallbladder and hepatic bile, the cholesterol saturation index was significantly lower in alcohol-fed animals, as was the ratio of trihydroxy to dihydroxy bile salts. The ethanol-supplemented diet produced a significant decrease in the absorption of water by the gallbladder as indicated by changes in the gallbladder bile to hepatic bile ratios of the total bile salt concentration (7.29 +/- 1.25 versus 3.84 +/- 0.56; p less than 0.05) and the total calcium (3.37 +/- 0.24 versus 2.43 +/- 0.29; p less than 0.05). These findings indicate that the protective effect of ethanol may be related to its ability both to inhibit gallbladder absorption of water and to alter the composition of biliary lipids.     

Alcohol protects against cholesterol gallstone formation.

Epidemiologic studies have suggested that alcohol intake may protect against cholelithiasis. Gallstone formation was studied in 20 prairie dogs fed a 0.4% cholesterol-supplemented liquid diet. In ten animals, ethanol provided 35% of total calories. In ten pair-fed controls, ethanol was replaced with isocaloric maltose. After 3 months the gallbladders were inspected for gallstones, and gallbladder bile was analyzed. Cholesterol macroaggregates were present in all controls and pigment concretions were noted in five. No stones were observed in ethanol-fed animals. Bile in the ethanol group contained less cholesterol than the controls (5.60 +/- 0.71 vs. 9.16 +/- 0.61 mmol/L, p less than 0.05) while phospholipids, total bile acids, and bilirubin were unchanged. The resulting cholesterol saturation index was reduced in the ethanol group (0.81 vs. 1.22, p less than 0.05). The ratios of trihydroxy to dihydroxy bile acids were also different (2.07 +/- 0.25 in ETOH vs. 3.29 in controls, p less than 0.05). The bile calcium concentration was higher in control animals presumably secondary to the use of complex sugars (5.36 +/- 0.37 vs. 3.77 +/- 0.32 mmol/L, p less than 0.05). These results confirm that ethanol inhibits cholesterol gallstone formation. They further suggest that this effect is dependent on reductions of biliary cholesterol and selective changes in bile acid concentrations.     

Bilirubin monoglucuronide promotes cholesterol gallstone formation

Recent evidence suggests that cholesterol (Ch) solubility in bile is determined by a complex interaction of mixed micelles and lecithin-cholesterol vesicles. Bilirubin monoglucuronide (BMG), which binds to bile salts and incorporates into mixed micelles, may displace cholesterol from micelles into vesicles, thus favoring cholesterol monohydrate crystal precipitation. Therefore, we designed an experiment to test the hypothesis that BMG may enhance cholesterol gallstone formation without inducing cholesterol supersaturation. For 8 weeks, 28 adult male prairie dogs were fed either a control, nonlithogenic diet (0.03% Ch), a high carbohydrate diet (CHO) which has no cholesterol but increases hepatic bilirubin secretion, or the same CHO diet plus 0.03% Ch. Cholecystectomy was then performed, and bile was examined microscopically for stones or crystals and analyzed for BMG and biliary lipids. Cholesterol saturation index was calculated. Cholesterol gallstones were found in none of the control animals and in 13% of the CHO-fed animals. However, the addition of trace cholesterol to the CHO diet resulted in an 88% incidence of cholesterol gallstones (P less than 0.001 vs control, P less than 0.01 vs CHO, respectively). Gallbladder bile was unsaturated with cholesterol in all groups. (control = 0.65 +/- 0.05, CHO = 0.46 +/- 0.05, CHO + 0.03% Ch = 0.70 +/- 0.03). CHO feeding alone or with trace cholesterol significantly elevated gallbladder bilirubin monoglucuronide, phospholipid, and cholesterol concentrations when compared to controls. These data suggest that in the prairie dog a high carbohydrate diet with only trace amounts of cholesterol increases bilirubin monoglucuronide in gallbladder bile and causes cholesterol gallstone formation without inducing cholesterol supersaturation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of amiloride on biliary calcium and cholesterol gallstone formation.

Recent studies indicate that gallbladder absorption increases during the early stages of experimentally-induced cholesterol gallstone formation. The purpose of the present study was to ascertain whether pharmacologic inhibition of gallbladder ion transport and absorption reduces the incidence of experimentally-induced cholesterol gallstones. Prairie dogs were fed either a control chow or a 1.2% cholesterol-enriched chow for 15 days. One group of cholesterol-fed animals received saline via an orogastric tube; another group received amiloride, a drug known to inhibit in vitro ion transport in the prairie dog gallbladder. The incidence of gallstones in cholesterol-fed animals was reduced from 83% to 13% (p less than 0.025) when the animals were treated with amiloride; this occurred despite a cholesterol-saturation index comparable to that observed in gallstone animals. Additionally, although biliary calcium decreased in the gallbladder, hepatic bile did not in the amiloride-treated animals. These data provide further evidence that altered gallbladder absorption and increased biliary calcium are important factors in the pathogenesis of cholesterol gallstones.     

Short-term fasting increases biliary calcium and bilirubin

Fasting has been associated clinically with the development of gallbladder sludge and pigment gallstones, both of which are composed primarily of calcium bilirubinate. Although fasting has been demonstrated to increase the cholesterol saturation of bile, its effect on biliary calcium and bilirubin has not been investigated. We, therefore, tested the hypothesis that short-term fasting would increase gallbladder bile calcium and bilirubin levels. Fifteen prairie dogs were studied. Seven animals were not fasted, whereas eight were fasted for 16 hr prior to acute experiments. Gallbladder and hepatic bile samples were obtained and analyzed for calcium, bilirubin, pH, and biliary lipids. Gallbladder bile ionized calcium levels were significantly increased in fasted animals (1.7 +/- 0.2 mM) compared to those in nonfasted animals (1.1 +/- 0.1 mM). Similarly, total calcium (4.3 +/- 0.5 mM vs 2.3 +/- 0.3 mM), total bilirubin (63 +/- 12 microM vs 29 +/- 8 microM), and bilirubin monoglucuronide (58 +/- 10 microM vs 22 +/- 8 microM) were significantly increased in the fasted group. Fasted animals were also noted to have an increased biliary cholesterol saturation index (0.57 +/- 0.04 vs 0.36 +/- 0.03) and decreased biliary pH (6.9 +/- 0.1 vs 7.6 +/- 0.1). These data indicate that in the prairie dog short-term fasting results in significant alterations in gallbladder bile composition. The increased concentrations of gallbladder calcium and bilirubin observed in these experiments may account, in part, for the formation of pigment gallstones and gallbladder sludge seen clinically with prolonged fasting.     

Ileal resection-induced gallstones: altered bilirubin or cholesterol metabolism?

Ileal resection has been shown to increase the risk of cholelithiasis. Earlier studies in humans suggested that ileal resection increases the cholesterol saturation index. Recent data from patients on long-term parenteral nutrition and from animals, however, have suggested that ileal resection predisposes to pigment gallstone formation. We therefore tested the hypothesis that ileal resection alters bile calcium and bilirubin metabolism without affecting the cholesterol saturation index. Adult male prairie dogs underwent either sham laparotomy (eight prairie dogs) or ileal resection (16 prairie dogs). All animals were fed a trace cholesterol (nonlithogenic) diet before and for 4 weeks after operation. Pigment gallstones were present in 44% of the ileal-resected animals and in none of the sham animals (p less than 0.05). Calcium bilirubinate crystals were present in 94% of the ileal-resected animals and in none of the sham animals (p less than 0.01). Gallbladder bile calcium (25.6 +/- 2.4 versus 17.2 +/- 1.1 mg/dl; p less than 0.05) and total bilirubin (29.3 +/- 4.0 versus 9.4 +/- 1.8 mg/dl; p less than 0.01) concentrations were significantly greater in ileal-resected animals. The cholesterol saturation index of gallbladder bile, however, was no different in ileal-resected (0.53 +/- 0.04) and in sham-operated animals (0.50 +/- 0.04). Although initial studies suggested that the cholesterol saturation index of hepatic bile was increased after ileal resection, a second set of experiments demonstrated that this phenomenon resulted from washout of bile salts that were already in extremely low concentrations in hepatic bile. We conclude that alterations in bilirubin, but not cholesterol, metabolism result in pigment gallstone formation after ileal resection.     

Altered bile composition during cholesterol gallstone formation: cause or effect?

Gallbladder stasis, increased gallbladder absorption, and elevated biliary levels of calcium, hydrogen ion, and bilirubin have been implicated as factors potentially critical to cholesterol crystal precipitation. Previous studies, however, have analyzed bile only when crystals or gallstones have already formed. Therefore, we tested the hypothesis that changes in bile composition are a late effect, occurring only after crystal formation. Adult male prairie dogs were fed a standard nonlithogenic control diet (n = 7) or a lithogenic 1.2% cholesterol diet for 5, 9, or 14 days to cause cholesterol saturation (n = 7), cholesterol monohydrate crystals (n = 7), or gallstones (n = 7). Gallbladder bile was examined microscopically for crystals, and analyzed for ionized calcium, bilirubin, pH, total protein, and biliary lipids. The ratio of gallbladder to hepatic bile radiolabeled cholic acid specific activity (Rsa) was calculated as an index of gallbladder stasis. Cholesterol saturation index was calculated. The results demonstrate that increased gallbladder bile cholesterol saturation and total protein concentration precede cholesterol monohydrate crystal precipitation. However, changes in gallbladder ionized calcium, unconjugated bilirubin, pH, stasis, and absorption were noted only after crystals and gallstones had already formed. These data indicate that alterations in gallbladder bile calcium, bilirubin, pH, stasis, and absorption are not early changes, but occur simultaneously with or after crystal formation. Increased biliary protein, however, which was elevated prior to nucleation, may be an important mediator of cholesterol precipitation in cholesterol-saturated bile.     

The effect of parenteral nutrition on biliary calcium and bilirubin

Recent studies have suggested that patients maintained on prolonged total parenteral nutrition (TPN) are at increased risk for gallstone formation. Animal and human data suggest that TPN causes calcium bilirubinate sludge and pigment gallstones. However, the effect of TPN on bile bilirubin and calcium concentrations has not previously been investigated. We, therefore, tested the hypothesis that TPN alters biliary bilirubin and calcium. Eight adult male prairie dogs received TPN (dextrose 15%, FreAmine III 4.25%, Intralipid 10%, insulin 25 U, electrolytes, and vitamins) at a rate of 80 cc/kg/day for 10 days. Eight additional animals maintained on a trace cholesterol diet served as controls. Gallbladder and hepatic bile samples were assayed for bilirubin and calcium. Cholesterol saturation index (CSI) and Rsa, a measure of gallbladder stasis, were also calculated. Calcium bilirubinate crystals were seen in gallbladder bile or wall scrapings of 7 of 8 TPN animals but in none of the controls (P less than 0.001). Animals that received TPN had bilirubin levels that were significantly higher in gallbladder bile (24.8 +/- 7.0 vs 5.1 +/- 0.9, P less than 0.05). Similarly, TPN animals had calcium levels that were significantly higher in gallbladder (30.0 +/- 3.6 vs 13.9 +/- 2.1, P less than 0.005) as well as hepatic (10.5 +/- 0.6 vs 7.4 +/- 0.6, P less than 0.005) bile. The Rsa values were also significantly lower (P less than 0.01) in TPN animals (0.57 +/- 0.07 vs 1.06 +/- 0.14). CSI, serum bilirubin, serum calcium, hematocrit, and reticulocyte counts did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of bile diversion and sphincterotomy on gallbladder muscle contractility and gallstone formation

Feeding prairie dogs a diet rich in cholesterol induces gallstone formation that is preceded by a sustained decrease in gallbladder smooth muscle contractility. Sphincterotomy is known to prevent gallstone formation in cholesterol-fed prairie dogs. Experiments were designed to determine whether the effect of sphincterotomy is a consequence of hepatic bile diversion, and whether bile diversion prevents the altered contractility. Following sham operation, surgical biliary enteric bypass, or sphincterotomy, prairie dogs were fed a high-cholesterol or a regular diet. Gallbladder muscle contractility and the presence of crystals and stones were determined. In sham-operated animals, the cholesterol diet induced a decrease in gallbladder muscle contractility and caused the formation of cholesterol gallstones. In animals with bile diversion and sphincterotomy, the effects of cholesterol feeding were reduced or prevented. Thus, these procedures may prevent stone formation by preventing a reduction in gallbladder contractility. Contractility was depressed in animals with bile diversion fed a regular diet, compared with animals with a sham operation fed a regular diet. The mechanism for this depression may differ from that induced by the cholesterol diet. Diversion, and perhaps sphincterotomy, impairs gallbladder filling. Thus, gallbladder muscle is not stretched and does not contract against a load. This could result in a "disuse atrophy." If the results from our study apply to humans, sphincterotomy may reduce stone formation by preventing the effects of lithogenic bile on gallbladder muscle contractility and by enhancing the ability of the muscle to empty the lithogenic bile.     

The effects of ethinylestradiol,a glucose diet and streptozotocin induced diabetes mellitus on gallstone formation and biliary lipid composition in the hamster

Possible risk factors for gallstone formation were examined and the concentrations of biliary lipids and each bile acid in the hepatic and gallbladder bile of hamsters were quantified. Forty female golden Syrian hamsters were divided into 4 groups according to diet; Group I, given control chow, Group II, given an ethinylestradiol and cholesterol supplemented diet, Group III, given a glucose rich diet without induced diabetes mellitus, and Group IV, given a glucose rich diet with diabetes mellitus induced by streptozotocin injection. The formation of cholesterol crystals but not gallstones was induced in Group II associated with a significantly decreased total bile acid concentration in the gallbladder bile but not in the hepatic bile. The formation of cholesterol gallstones and crystals with significantly higher concentrations of cholesterol and phospholipid was observed in Group III, while neither the formation of gallstones nor lithogenicity was enhanced by diabetes mellitus. However, a quite different lithogenicity was evident between the hepatic and gallbladder bile of the Group IV animals. These results suggest that neither the consumption of oral contraceptives nor diabetes mellitus induces gallstone formation, but that these factors can be responsible for dysfunction of the gallbladder.     

The prevention of experimental cholesterol gallstones by ileectomy in mice

After a lithogenic diet containing 0.5 per cent cholesterol and 0.25 per cent sodium cholate was fed to a group of normal Crj-ICR male mice for 10 days, cholesterol gallstones developed. No formation of gallstones occurred, however, in a group of mice from which 20 cms of terminal ileum had been removed prior to the feeding of the lithogenic diet. The biliary concentrations of cholesterol, phospholipids and bile acids were markedly lower in the ileectomized mice, with the decrease in cholesterol concentration being most significant. On the other hand, fecal excretion of sterols and bile acids increased in the ileectomized mice. The pool size of bile acids increased after the feeding of the lithogenic diet, but ileectomy decreased the pool size in mice fed the ordinary or lithogenic diets. The biliary concentration of cholic acid increased after the feeding of the lithogenic diet, but decreased with ileectomy. The biliary concentration and fecal excretion of deoxycholic acid markedly increased, while those of beta-muricholic acid and its secondary bile acids, omega-muricholic acid and hyodeoxycholic acid, decreased. The increase in plasma and liver cholesterol levels after the feeding of the lithogenic diet was prevented by ileectomy. These data suggest that ileectomy prevents the formation of cholesterol gallstones after the feeding of a lithogenic diet due to a decrease in cholic acid absorption.     

The effects of ethinylestradiol, a glucose diet and streptozotocin induced diabetes mellitus on gallstone formation and biliary lipid composition in the hamster

Possible risk factors for gallstone formation were examined and the concentrations of biliary lipids and each bile acid in the hepatic and gallbladder bile of hamsters were quantified. Forty female golden Syrian hamsters were divided into 4 groups according to diet; Group I, given control chow, Group II, given an ethinylestradiol and cholesterol supplemented diet, Group III, given a glucose rich diet without induced diabetes mellitus, and Group IV, given a glucose rich diet with diabetes mellitus induced by streptozotocin injection. The formation of cholesterol crystals but not gallstones was induced in Group II associated with a significantly decreased total bile acid concentration in the gallbladder bile but not in the hepatic bile. The formation of cholesterol gallstones and crystals with significantly higher concentrations of cholesterol and phospholipid was observed in Group III, while neither the formation of gallstones nor lithogenicity was enhanced by diabetes mellitus. However, a quite different lithogenicity was evident between the hepatic and gallbladder bile of the Group IV animals. These results suggest that neither the consumption of oral contraceptives nor diabetes mellitus induces gallstone formation, but that these factors can be responsible for dysfunction of the gallbladder.     

The prevention of experimental cholesterol gallstones by ileectomy in mice

After a lithogenic diet containing 0.5 per cent cholesterol and 0.25 per cent sodium cholate was fed to a group of normal Crj-ICR male mice for 10 days, cholesterol gallstones developed. No formation of gallstones occurred, however, in a group of mice from which 20 cms of terminal ileum had been removed prior to the feeding of the lithogenic diet. The biliary concentrations of cholesterol, phospholipids and bile acids were markedly lower in the ileectomized mice, with the decrease in cholesterol concentration being most significant. On the other hand, fecal excretion of sterols and bile acids increased in the ileectomized mice. The pool size of bile acids increased after the feeding of the lithogenic diet, but ileectomy decreased the pool size in mice fed the ordinary or lithogenic diets. The biliary concentration of cholic acid increased after the feeding of the lithogenic diet, but decreased with ileectomy. The biliary concentration and fecal excretion of deoxycholic acid markedly increased, while those of β-muricholic acid and its secondary bile acids, ω-muricholic acid and hyodeoxycholic acid, decreased. The increase in plasma and liver cholesterol levels after the feeding of the lithogenic diet was prevented by ileectomy. These data suggest that ileectomy prevents the formation of cholesterol gallstones after the feeding of a lithogenic diet due to a decrease in cholic acid absorption.     

The effects of lithogenic bile on gallbladder epithelium.

Prairie dogs were fed a 1.2% cholesterol diet for up to 24 weeks to evaluate the effects of lithogenic bile on the mucosa of the gallbladder. There was a progressive increase in the lithogenic index of the gallbladder bile (1.44 +/- 0.15 at 4 weeks, p less than 0.05). Fifty-five of 70 animals developed gallstones between the second and fourth week. Increasing stone burden was associated with a 27% (p less than 0.05) decrease in the electrical resistance of the epithelium and a 60% (p less than 0.05) decrease in net sodium transport when measured isotopically in an Ussing chamber (3 weeks). After 4 months, seven of ten animals developed inflammatory mucosal polyps characterized by a heavy infiltration of plasma cells into an expanded matrix. Cellular infiltration began as early as 2 weeks. These changes occurred without alterations in the ultrastructural appearance of the epithelium.     

Hyodeoxycholic acid: a new approach to gallstone prevention

Hyodeoxycholic acid and its isomer, 6 beta-hyodeoxycholic acid, when added to a lithogenic diet prevented the formation of cholesterol gallstones and crystals in prairie dogs. This beneficial effect occurred in the presence of bile supersaturated with cholesterol. Hyodeoxycholic acid abolished the feedback inhibition of hepatic hydroxymethylglutaryl coenzyme A reductase activity, the rate-limiting enzyme of cholesterol synthesis, and prevented elevations in serum and liver cholesterol observed in animals fed a 0.4 percent cholesterol diet. The gallbladder bile of the animals fed hyodeoxycholic acid and 6 beta-hyodeoxycholic acid contained abundant liquid crystals. This suggests that these bile acids prevented the transition of cholesterol from its liquid crystalline phase to solid crystals and stones.     

The role of dietary iron in pigment gallstone formation

Recent studies suggest that dietary factors may be responsible for the increasing incidence of pigment gallstones. Although iron deficiency alters the activities of several hepatic enzymes, its effects on biliary lipid metabolism are not known. The aim of this study was to define the role of dietary iron in pigment gallstone formation. Three groups of prairie dogs were maintained for 2 months on either a control chow (iron-198 ppm), a high-carbohydrate diet with normal iron levels (CHO group; iron-220 ppm), or a high-carbohydrate, iron-deficient (iron-56 ppm) diet (CHO-FeD group). Serum analysis confirmed iron deficiency in the CHO-FeD group. The CHO animals had a significant (p less than 0.01) increase in hepatic bile phospholipids, while CHO-FeD animals had increased (p less than 0.01) concentrations of phospholipids and cholesterol as compared with controls. Similar findings were noted in gallbladder bile with the addition of increased calcium levels in both carbohydrate groups. Calcium bilirubinate crystals and stones were found in only 17% of CHO animals, as compared with 67% of CHO-FeD animals. These data indicate that consumption of diets rich in carbohydrates but deficient in iron alters hepatic metabolism of cholesterol and may be an important etiologic factor in pigment gallstone formation. Iron supplementation may prevent pigment gallstones in certain high-risk groups.     

Cholecystokinin prophylaxis of parenteral nutrition-induced gallbladder disease.

Recent studies indicate that long-term total parenteral nutrition (TPN) induces gallstone formation and acalculous cholecystitis in humans. Cholecystectomy is hazardous for these patients because they frequently have multiple medical problems and have undergone numerous abdominal operations. The present study was designed to develop a method to prevent TPN-induced gallbladder disease. The authors tested the hypothesis that a single daily intravenous infusion of cholecystokinin-octapeptide (CCK-OP) will prevent TPN-induced gallbladder stasis. Eleven prairie dogs received TPN for 10 days. Six of these animals were given a daily infusion of CCK-OP. Control animals were fed ad lib. Each animal's bile salt pool was labeled with intravenous 3H-cholic acid 16 hours prior to acute terminal experiments. The ratio of gallbladder to hepatic bile 3H-cholic acid specific activity (Rsa) provides an index of gallbladder stasis. A Rsa of less than 1.0 indicates gallbladder stasis. TPN animals had a Rsa of 0.54 +/- 0.13 (p less than 0.01 vs. controls), indicating stasis of bile in the gallbladder. Daily CCK-OP infusions resulted in a Rsa of 0.92 +/- 0.10 (p less than 0.05 vs. TPN without CCK-OP), indicating that TPN-induced gallbladder stasis is prevented by daily CCK-OP. Control animals had a Rsa of 1.03 +/- 0.06. The cholesterol saturation indices of gallbladder and hepatic bile were not increased by TPN or CCK-OP. These data indicate that 1) TPN induces gallbladder stasis but does not increase bile lithogenic index; and 2) daily injections of CCK-OP prevent TPN-induced gallbladder stasis.     

Altered biliary prostaglandins and cholesterol gallstones: an in vivo study

Recent investigations suggest that biliary prostaglandin metabolism is altered during cholesterol gallstone formation. Most of the available data, however, has been obtained from in vitro studies. The purpose of the present study was to define the effects of cholesterol gallstone formation on in vivo biliary prostaglandin metabolism. Male prairie dogs were fed either a control chow for 21 days or a 1.2% cholesterol-enriched chow for 14-21 days. Cholecystectomy was performed and gallbladder tissue and bile were collected for analysis of prostaglandin concentrations using radioimmunoassay techniques. Gallbladder bile was examined for the presence of crystals and stones. No control animals but all cholesterol-fed animals developed either cholesterol crystals or gallstones (P less than 0.001). Concentrations of prostaglandin E2, prostaglandin F2 (PGF2 alpha), and the stable metabolic products of prostacyclin and thromboxane A2, 6-keto-PGF1 alpha and thromboxane B2 (TXB2), respectively, were decreased 60-85% in the gallbladder tissue of animals with crystals and gallstones compared to controls. Additionally, gallstone containing animals and those with crystals demonstrated a significant increase in the gallbladder bile concentrations of PGF2 alpha, 6-keto-PGF1 alpha, and TXB2. These findings lend support to previously reported in vitro studies suggesting that prostaglandin synthesis increases at an early stage of experimentally induced cholesterol gallstone formation.     

Pigment gallstone formation and altered ion transport

Feeding corn and alfalfa to young prairie dogs resulted in formation of gallstones composed of 45 percent cholesterol, 30 percent bile pigments, and 25 percent calcium bilirubinate in half of the animals. This diet also resulted in increased gallbladder bile concentrations of calcium, phospholipids, and cholesterol. Although the cholesterol saturation index was significantly increased compared with control subjects, it remained less than 1. In addition to the changes in biliary lipid composition, the corn and alfalfa-fed animals had significantly decreased transepithelial potential difference and short-circuit current when compared with control animals. These are changes in gallbladder mucosal function similar to those that have been reported in humans with gallstones. This model may therefore prove to be of great value in studying the pathogenesis of noncholesterol gallstones.     

Effects of resection or bypass of the distal ileum on the lithogenicity of bile

Changes in the composition and lithogenicity of gallbladder bile after resection and bypass of the distal ileum were investigated in the prairie dog. In animals fed a trace cholesterol diet, both ileal resection and ileal bypass increased the cholesterol saturation of bile. In animals fed a cholesterol-enriched diet, the cholesterol saturation was increased by ileal resection but not by ileal bypass. In the animals fed the trace cholesterol diet, both ileal resection and ileal bypass induced the formation of bilirubinate gallstones.