Early stages of gallstone formation in guinea pig are associated with decreased biliary sensitivity to cholecystokinin

The purpose of this study was to measure differences in gallbladder sensitivity to cholecystokinin (CCK)in vivo during the early stages of gallstone formation and to correlate these findings to gallbladder CCK receptors. Guinea pigs were placed on either a normal diet or a two-week cholelithogenic diet, after which gallbladder emptying pressure to exogenously administered CCK was measuredin vivo, according to the presence or absence of gallstones. At all doses of CCK tested (except 10^–10 mol/kg), the gallbladder response to CCK of guinea pigs that did not develop gallstones (on the cholelithogenic diet) was more sensitive than that of guinea pigs that did develop gallstones. Neither group was different from guinea pigs on a normal diet. In a second experiment, CCK receptors were measured on gallbladder muscularis from guinea pigs after two weeks on the same diet as in the first experiment. Those guinea pigs that did not develop gallstones had greater concentrations of CCK receptors (149±9 fmol/mg protein) than those that did develop gallstones (70±23 fmol/mg protein). Neither group was different from normal diet guinea pigs (119±57 fmol/mg protein). At the time point measured, there were no differences in the lipid chemistry, or protein concentrations of gallbladder bile between the guinea pigs on the cholelithogenic diet that did or did not develop gallstones, or those on normal guinea pig chow. We conclude that the early stages of gallstone formation in guinea pigs are associated with decreased gallbladder sensitivity to CCK and that this change may be due to a lower concentration of CCK receptors on the gallbladder smooth muscle.Supported by the Wellcome Foundation, Ethicon Foundation, and British Digestive FoundationSupported by grants from the National Institutes of Health (5R37 DK 15241-19, P01 DK 35608, and CA 38657)     

Comparison of effects of cholecystokinin and erythromycin on bile chemistry and gallstone formation in aged guinea pigs.

BACKGROUND: There has been considerable interest in gall bladder motility in recent years. We compared the effects of cholecystokinin (CCK) and erythromycin on bile chemistry and gallstone formation in aged guinea pigs. METHODS: Two groups of guinea pigs (1-mo and 3-y old; n=40 each) were studied. Each group was divided into four subgroups of 10 animals each; one subgroup received lithogenic diet, one each received CCK or erythromycin daily in addition to lithogenic diet for 4 weeks, and one received normal diet. After 4 weeks, the presence of gallstones or sludge was recorded and bile composition including concentrations of bile acid, cholesterol, lecithin and protein concentrations was studied. RESULTS: No gallstones were observed in the 1-mo-old animals. In the 3-year-old animals, 9 of 10 guinea pigs on lithogenic diet and 4 of 10 in each treatment subgroup and the normal diet subgroup developed gallstones. CCK and erythromycin had similar effects on bile chemistry and stone formation. CONCLUSIONS: Aging increases the formation of gallstones in guinea pigs. Erythromycin is as effective as CCK in reducing gallstone formation by improving gall bladder motility.     

Gallbladder filling and emptying during cholesterol gallstone formation in the prairie dog. A cholescintigraphic study

We studied gallbladder bile flow before, during, and after cholesterol gallstone formation in the prairie dog using infusion cholescintigraphy with 99mTc-diethyl iminodiacetic acid. In 18 fasting animals partitioning of bile between gallbladder and intestine was determined every 15 min for 140 min, and gallbladder response to cholecystokinin (5 U/kg X h) was calculated from the gallbladder ejection fraction. Ten prairie dogs were then placed on a 0.4% cholesterol diet and 8 on a regular diet, and the studies were repeated 1, 2, and 6 wk later. The proportion of hepatic bile that entered the gallbladder relative to the intestine varied from one 15-min period to the next, and averaged 28.2% +/- 5.1% at 140 min. Partial spontaneous gallbladder emptying (ejection fraction 11.5% +/- 5.6%) was intermittently observed. Neither the number nor the ejection fraction of spontaneous gallbladder contractions changed during gallstone formation. By contrast, the percent of gallbladder emptying in response to cholecystokinin decreased from 72.1% +/- 5% to 25.9% +/- 9.3% (p less than 0.025) in the first week and was 14.3% +/- 5.5% at 6 wk (p less than 0.01 from prediet values, not significant from first week). Gallbladder filling decreased from 28.2% +/- 5.1% to 6.7% +/- 3% (p less than 0.01), but this change was only observed after 6 wk, when gallstones had formed. This study shows that bile flow into the gallbladder during fasting is not constant; the gallbladder contracts intermittently; gallbladder emptying in response to exogenous cholecystokinin is altered very early during gallstone formation; and gallbladder filling remains unaffected until later stages, when gallstones have formed.     

中药胆宁片治疗胆囊胆固醇结石作用机制的实验研究

[目的]探讨胆宁片对胆固醇结石豚鼠胆汁中黏蛋白及血清IL-2水平的影响.[方法]雌性豚鼠60只,体重（300±20）g,随机分为空白组、模型组、胆宁片组和熊脱氧胆酸组,每组15只;除空白组外,采用“高胆固醇致石食饵诱发法”建立豚鼠胆固醇结石模型,并于造模成功后分别对各治疗组予药物干预,胆宁片组灌服胆宁混悬液0.52 g· kg-1·d-1,熊脱氧胆酸组灌服熊脱氧胆酸混悬液0.05 g·kg-1·d-1,模型组与空白组均灌服等容量的生理盐水,8周后观察各组豚鼠一般情况、胆汁中黏蛋白及血清IL-2水平.[结果]胆宁片可显著降低豚鼠胆固醇结石成石率,并能显著降低胆囊黏蛋白及血清IL-2水平（P＜0.05,P＜0.01）.[结论]胆宁片能直接调节胆囊黏蛋白等相关促成核因子,同时能通过调节血清中IL-2间接调控胆囊黏蛋白水平,从而调控成核过程,对胆囊胆固醇结石有一定的治疗作用.     

Gallbladder function during gallstone dissolution. Effect of bile acid therapy in patients with gallstones

Impaired gallbladder emptying has been associated with gallstone disease but any effect on or from bile acid therapy for gallstone dissolution is unknown. We evaluated gallbladder filling and emptying with low-dose cholecystokinin infusion (0.02 U/kg.h) by computer-assisted cholescintigraphy in 52 controls versus 31 gallstone patients: 17 treated with 12-15 mg/kg.day of chenodeoxycholic acid and 14 with 8-10 mg/kg.day of ursodeoxycholic acid. Thirteen of 31 patients with complete dissolution had four scans: before, after 3 mo of therapy, after stone dissolution, and after discontinuation of bile acids. The 18 failures had three scans: before and after 3 and 15-18 mo of therapy. Before therapy, the 31 gallstone patients had significantly impaired gallbladder emptying compared with controls, but filling was not decreased. Bile acids significantly decreased emptying in both treatment groups after 3 mo of therapy. In the dissolution group, emptying improved once the stones had dissolved and increased further upon discontinuing the bile acids. In the failures, impaired emptying persisted for up to 15-18 mo. Gallbladder filling in the 31 gallstone patients was also significantly decreased after 3 mo of bile acid therapy, particularly in the failure patients, 5 of whom exhibited zero filling. No differences were detected between ursodeoxycholic acid and chenodeoxycholic acid for either gallbladder function or efficiency of dissolution. Thus, bile acid therapy impairs gallbladder filling and emptying in gallstone patients. Gallstone dissolution improves emptying, which is further enhanced when bile acids are discontinued.     

Endogenous Hypercholecystokininemia,But Not Aspirin,Reduces the Gallstone Incidence in the Hamster Model

Borch K, Chu M, Kullman E, Carlsson B, Rehfeld JF. Endogenous hypercholecystokininemia, but not aspirin, reduces the gallstone incidence in the hamster model. Scand J Gastroenterol 1994;29:740-743.

Background: Studies in humans and rodents indicate that gallstone development may be prevented by inhibiting gallbladder mucus hypersecretion with non-steroidal anti-inflammatory drugs or by preventing stasis of gallbladder bile with administration of cholecystokinin. Methods: The effect of oral aspirin and pancreaticobiliary diversion with endogenous hypercholecystokininemia on crystal and gallstone formation was studied in Syrian golden hamsters fed a lithogenic diet for 8 weeks. Results: None of the control animals fed a normal diet developed gallstones or crystals in gallbladder bile. Gallstones developed in 67% of the animals fed a lithogenic diet only. The gallstone prevalence did not differ significantly in animals on a lithogenic diet and a daily aspirin dose of 6 mg/kg (gallstone prevalence, 60%) or 100 mg/kg (gallstone prevalence, 70%), whereas it was significantly lower in animals with endogenous hypercholecystokininemia on a lithogenic diet (gallstone prevalence, 29%). The prevalence of crystals in gallbladder bile did not differ significantly between any of the experimental groups. Conclusions: It is concluded that in hamsters on a lithogenic diet, aspirin does not prevent gallstone formation, whereas endogenous hypercholecystokininemia reduces the prevalence of stones without affecting the occurrence of crystals in gallbladder bile.     

Abnormal gallbladder emptying in a subgroup of patients with gallstones

Gallbladder stasis has been implicated in gallstone formation. Gallbladder filling and emptying were quantitated by computer-assisted cholescintigraphy in 41 normal subjects versus 26 patients with gallstones. Gallbladder contraction was induced by low-dose (1.2 U/kg . h) cholecystokinin infusion. Gallstone patients exhibited normal gallbladder filling, but emptying was significantly (p less than 0.01) reduced compared with controls. On closer inspection, the patients fell into two subgroups, separated by t1/2, the time to empty 50% of gallbladder contents, 19.1 min (mean + 2 SD of control). Fifteen patients (57.7%) with a normal t1/2 (less than 19.1 min) exhibited both normal filling and normal emptying. The remaining 11 patients (43.3%) with t1/2 greater than 19.1 min had grossly abnormal gallbladder emptying, significantly (p less than 0.001) different from both the previous patient subgroup and the controls. There was no significant difference in age, sex, prevalence of obesity, presence or absence of biliary colic, and gallstone size, number, or calcification between these two subgroups. Thus, defective gallbladder emptying is evident in a subgroup of gallstone patients, and is independent of clinical features, stone size, and number. Impaired emptying should be considered when assessing pathogenesis or medical therapy.     

Impaired gallbladder mucosal function in aged gallstone patients suppresses gallstone recurrence after successful extracorporeal shockwave lithotripsy

BACKGROUND: Absorption of water, as well as emptying of bile, are important functions of the gallbladder. We studied the changes of gallbladder function with age in gallstone patients and their influence on the outcome of extracorporeal shockwave lithotripsy (ESWL). METHODS: (i) A total of 123 consecutive patients with complete stone clearance by ESWL were examined. Gallbladder emptying was assessed before treatment using intravenous cholecystography. After stone clearance, the recurrence of gallstones was monitored by using ultrasonography. Cox regression analysis was used to determine the risk factors associated with stone recurrence. (ii) Gallbladder bile was sampled from 59 gallstone patients during surgery. Biliary cholesterol, phospholipids, and total bile acids were simultaneously quantified by using gas-liquid chromatography. RESULTS: Impaired gallbladder function, but not gallstone recurrence, was more frequently observed in older patients (>/=65 years old) than in younger patients (<65 years old). Cox regression analysis revealed that poor gallbladder emptying was an independent predictor of stone recurrence after ESWL in the total study population, but not in the older patients (>/=65 years old). Analysis of bile from surgically treated patients with cholesterol stones showed a significantly higher total lipid concentration and a shorter nucleation time in the younger group (<65 years old), but the cholesterol saturation index did not differ between the younger and older groups. CONCLUSIONS: Our data suggest that the reduced concentrating function of the gallbladder in elderly gallstone patients helps to counteract stone recurrence despite their abnormal gallbladder motility. Therefore, aged gallstone patients may be preferentially treated by a non-surgical strategy.     

胆胃舒颗粒对胆囊血管活性肠肽受体基因表达的影响

[目的]观察胆胃舒颗粒对胆囊血管活性肠肽(vasoactive intestinal peptide,VIP)受体基因表达的影响及预防胆囊结石的作用.[方法]雄性豚鼠90只,随机分为3组,每组30只,空白组喂养普通饲料40 g/(d·只);模型组喂养胆固醇结石诱石饲料40 g/(d·只);治疗组喂养胆固醇诱石饲料40 g/(d·只),加胆胃舒颗粒溶液1.5ml(含300mg胆胃舒颗粒)灌胃.实验2个月后观察3组胆囊结石情况、胆囊收缩功能及胆囊壁VIP受体基因表达.[结果]胆囊结石形成率:空白组3.33％(1/30),模型组92.59％(25/27),治疗组10.71％(3/28);胆囊收缩功能:空白组胆囊收缩率为(66.83± 5.34)％,模型组(43.06±4.27)％,治疗组(67.93±6.82)％;胆囊壁VIP受体基因表达:空白组0.30±0.07,模型组0.45±0.12,治疗组0.33±0.06.差异均有统计学意义(P＜0.05).[结论]胆胃舒颗粒可降低胆囊结石的形成,其作用机制可能通过降低胆囊壁VIP受体基因表达,从而加强胆囊收缩功能,促使胆汁排泄,防止胆囊结石的发生.     

The effect of proglumide on gallstone formation in guinea pigs

In this study, the chronic effects of proglumide (PGM, a cholecystokinin/gastrin receptor antagonist) on gallstone formation and hepatic bile secretion were investigated as follows: Group 1: Fed with low protein (14%) lithogenic diet. Group 2: Fed with the same lithogenic diet and was given PGM (250 mg/kg, bid, p. o.). Group 3: Fed with commercial guinea pig chow (protein content 22%). Eight weeks later the animals were operated under urethane anesthesia, the gallbladders were removed and examined for gallstones. Meanwhile, by bile duct cannulation, the hepatic bile flow and bile contents were measured. It was found that: (1) the animal model was valid for the purpose specified; (2) the rate of gallstone formation was significantly lower in PGM group than in the controls (17.5% vs 56.8%, P less than 0.01); and (3) PGM significantly enhanced the flow rates and electrolyte contents and decreased the unconjugated bilirubin content of the hepatic bile. It is concluded that PGM may suppress gallstone formation in guinea pigs on lithogenic diet, and this may be related to its stimulatory effect on hepatic bile secretion and to its ability to induce a decrease in unconjugated bilirubin in the hepatic bile.     

Gallbladder motility in cholesterol gallstone disease. Effect of ursodeoxycholic acid administration and gallstone dissolution

Gallbladder motility was evaluated by ultrasonography in 75 cholesterol gallstone patients and in 77 matched control subjects. All 75 gallstone patients were candidates for oral bile acid therapy (radiolucent gallstones, less than 2 cm in diameter, in well-opacified gallbladder), and 38 of them were also studied during ursodeoxycholic acid administration. An additional 20 gallstone patients were studied 1 year after confirmed gallstone dissolution with oral bile acids. Gallstone patients showed significantly greater fasting and residual volumes, a decreased percent of gallbladder emptying, but a similar absolute emptying and emptying rate compared with the control subjects. Greater fasting volumes and reduced percents of gallbladder emptying were also found in gallstone-free patients who achieved complete dissolution with oral bile acids. After ursodeoxycholic acid administration, fasting gallbladder volumes were greater, and percents of gallbladder emptying were further decreased than in untreated gallstone patients. In conclusion, greater fasting volumes, and not reduced gallbladder contractility, account for the defective gallbladder function in radiolucent (cholesterol-rich) gallstone patients. This condition is likely to precede, and possibly to promote, gallstone formation because it persists after gallstone dissolution. Ursodeoxycholic acid administration worsens the defect observed in gallstone patients. This finding also suggests, although indirectly, that the expected normalization of cholesterol saturation during oral bile acid administration is not paralleled by an improvement in gallbladder function.     

Can pigment gallstones be induced by biliary stricture and prevented by medicine in Guinea pigs？

AIM: To determine the relationship between biliary stricture and pigment gallstone formation, and the prevention of pigment gallstones with medicine. METHODS: One hundred and eighteen male guinea pigs were randomly divided into four groups: stricture group (S, n = 30) underwent partial ligation of common bile duct, and fed on regular chow; S plus medicine group (S+M, n = 27) underwent the same operation but fed on medicinal chow (0.3 g chenodeoxycholic acid, 0.5 g glucurolactone, and 0.5 g aspirin were mixed up in 1.2 kg regular chow); medicinal control group (C+M, n = 30) was free of operation, and fed on medicinal chow; and control group (C, n = 31) was free of operation and fed on regular chow. One week later, laparotomy was performed, and the bile of gallbladder was collected, measured, and cultured. RESULTS: Gallstones were identif ied. Pigment gallstones were induced by biliary stricture in 95% (22/23) of S group. In the S+M group, the incidence of gallstone was reduced to 55% (11/20, vs S group, P < 0.01). The changes of indirect bilirubin and ionized calcium in the bile were consistent with gallstone incidences. CONCLUSION: Biliary stricture can cause pigment gallstone formation in guinea pigs, and the medicines used can lower the incidence of gallstones. The bilirubin and ionized calcium play important roles in pigment gallstone formation.     

Gallbladder dysfunction in diabetes mellitus

To further elucidate the mechanism of impaired gallbladder emptying in diabetics with and without neuropathy, gallbladder function was assessed by ultrasonography following a medium-chain triglyceride (lipomul, 1.5 mg/kg) infusion into the duodenum and compared to that during intravenous infusion of cholecystokinin in diabetic women. Results were compared with five healthy control women. Mean (±sd) maximal percent gallbladder volume in diabetics following lipomul was reduced to 49±8% and after intravenous cholecystokinin to 47±9%, which was less than those in controls, 21±9% and 24±6%, respectively, but not significantly different. Further analysis of gallbladder emptying to lipomul differentiated two subgroups of diabetics: one subgroup (N=5) had emptying comparable to controls (responders), while the other (N=5) had very modest emptying (nonresponders). Two of the patients in the latter group had normal gallbladder emptying during exogenous cholecystokinin and their response would be compatible with visceral neuropathy. Blood levels of cholecystokinin, measured by bioassay, following lipomul and exogenous cholecystokinin were similar in controls and diabetics. Presence of diabetic neuropathy did not correlate with impaired gallbladder emptying. Follow up at 6 and 12 months of the three nonresponder diabetics revealed that no gallstones had developed and that two of them became responders to exogenous cholecystokinin. We conclude that: (1) following lipomul, about 50% of diabetics in this study have impaired gallbladder emptying, which is not strictly correlated with diabetic neuropathy; (2) this was not due to abnormal cholecystokinin release; (3) in diabetic patients with impaired gallbladder emptying another abnormality may be present in the gallbladder; and (4) impaired gallbladder contraction may not lead to gallstone formation in one-year follow-up.     

Effect of dietary cholesterol and indomethacin on cholelithiasis and gallbladder motility in guinea pig

This study examines the effects of dietary cholesterol and subcutaneous indomethacin on gallstone formation, gallbladder motility, and bile composition in guinea pigs. Guinea pigs on cholesterol diets developed gallstones which were not primarily composed of cholesterol and were not prevented by indomethacin. Animals receiving cholesterol diets showed significant gallbladder enlargement which was inhibited by indomethacin. Cholesterol did not alter gallbladder pressure-volume relationships or the response to CCK, while indomethacin diminished gallbladder tone. Although cholesterol feeding did not appear to alter smooth muscle contractility in the guinea pig gallbladder, it caused significant gallbladder enlargement by a mechanism which may be dependent on prostaglandins.This study was supported by National Institutes of Health grant AM 15304.     

Gallbladder motility and lithogenicity of bile in patients with choledocholithiasis after endoscopic sphincterotomy

Background/Aims: Ablation of the sphincter of Oddi has been shown to inhibit gallstone formation in the prairie dog model, probably by allevaiting gallbladder bile stasis. The effect of endoscopic sphincterotomy (ES) on gallbladder emptying and lithogenicity of bile has not been studied adequately in humans. We, therefore, studied the changes in gallbladder emptying and lithogenicity of bile following ES in patients with choledocholithiasis and gallbladder in situ.Methods: Thirteen patients with choledocholithiasis with intact gallbladder underwent ES and common bile duct clearance. Eight patients had concomitant gallstones. Gallbladder emptying was studied by real time ultrasonography after stimulation by ceruletid infusion. Fasting gallbladder bile was collected during endoscopic retrograde cholangiography by placing a 7F or 8F catheter in the common bile duct and after ceruletid stimulation of gallbladder for bile microscopy and cholesterol nucleation time determination. Gallbladder emptying, nucleation time and bile microscopy were performed before ES and again between 4 and 8 weeks after ES after cholangiographic confirmation of clearance of common bile duct stones.Results: Fasting and residual gallbladder volumes decreased and ejection fraction increased significantly following ES, suggesting decreased stasis and improved emptying of gallbladder. Nucleation time was prolonged and cholesterol crystal index in bile decreased after ES, suggesting decreased lithogenicity. The decrease in gallbladder volumes and increase in ejection fraction after ES were observed in both groups of patients, with or without concomitant gallstones.Conclusions: ES decreases the stasis of gallbladder bile, improves gallbladder emptying and decreases the lithogenicity of bile in patients with gallstone disease as reflected by prolongation in nucleation time. ES may find a role as an adjunct to oral bile acid therapy and extracorporeal shock wave lithotripsy in addition to a prophylactic role of preventing gallstone formation in high risk groups.     

Influence of gallstones and ursodeoxycholic acid therapy on gallbladder emptying

Altered gallbladder motility could predispose to, or result from, gallstone formation and could also explain the alleged relief of biliary colic seen during bile acid therapy. Therefore, in 14 controls, 25 patients with radiolucent gallstones, and 14 patients with radiopaque gallstones, we used two techniques to measure gallbladder contraction--radionuclide imaging and real-time ultrasound--in response to one of two stimuli--a Lundh meal or intravenous cholecystokinin-octapeptide. Using the radionuclide technique, postprandial gallbladder emptying (t1/2) was prolonged (p less than 0.01) both in patients with radiopaque (26.7 +/- 3.1 min, mean +/- SEM) and radiolucent (21.7 +/- 3.1) gallstones when compared with controls (10.2 +/- 1.5). In patients with radiolucent stones, the t1/2 of gallbladder emptying became further prolonged (p less than 0.05) after 1 mo of therapy with 8-10 mg/kg body wt X day of ursodeoxycholic acid, to 32.1 +/- 4.4 min. A similar pattern of results was seen after cholecystokinin-octapeptide and also with real-time ultrasound. Thus, after both stimuli and using two independent techniques, gallbladder contraction was reduced in patients with gallstones. The slower and less complete gallbladder emptying with ursotherapy might explain the reduction in biliary colic noted during treatment.     

Influence of fever on biliary elements of guinea pigs

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Changes of gastrointestinal myoelectric activity and bile acid pool size after cholecystectomy in guinea pigs

AIM: To investigate the bile acid pool size after cholecystectomy whether or not correlated to the gastrointestinal migrating myoeiectric complex (MMC) in guinea pigs. METHODS: Gallbladder motilities were assessed before cholecystectomy. Furthermore, we continuously monitored interdigestive gastrointestinal motilities using bipolar electrodes in conscious guinea pigs before and after surgery at 4 wk in standard diet group and high cholesterol diet (cholesterol gallstone) group. Total bile acid pool sizes were measured by isotope dilution method at meantime. RESULTS: After cholecystectomy, there were parallel falls in duration of phase Ⅰ, Ⅱ, Ⅲ and MMC cycle duration but increase in amplitude in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones. However, There were not significantly differences. On the other hand, the bile acid pool was definitely small in the GS guinea pigs compared to normal guinea pigs and became slightly smaller after cholecystectomy. Similarly, bile acid in gallbladder bile, fecal bile acid was slightly increased in GS guinea pigs after cholecystectomy, to the same degree as normal. These differences, however, were not significant. CONCLUSION: It is concluded that in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones: (1) Cholecystectomy produce a similar but less marked trend in bile acid pool; and (2) MMC are linked to enterohepatic circulation of bile acids, rather than surgery, which is consistent with changes of the bile acid pool size. As a result, gastrointestinal dyskinesia is not involved in occurrence of postchole cystectomy syndrome.     

Gallbladder Motility and Lithogenesis in Obese Patients During Diet-Induced Weight Loss

Obesity and weight loss are important risk factors for gallstone development. The mechanisms involved are unknown. We prospectively studied changes in gallbladder (GB) emptying and bile composition during weight loss. We studied 12 alithiasic obese subjects who entered a six-month diet program (800–1200 kcal/day, 26 g fat/day). As controls we evaluated 12 healthy nulliparous nonobese young women. GB volumes were studied by ultrasonography (fasting volume, GBFV; residual volume after a liquid meal, GBRV) at entry and after 4 and 20 weeks of dieting. Bile acid pool size, biliary lipid composition, presence of cholesterol crystals, and nucleation time were also studied. Of 12 obese subjects studied (mean BMI 35.1 kg/m²), 10 remained in the program for six months, but only six completed the entire study protocol, obtaining a significant weight loss (BMI: 31.2 kg/m², P < 0.001). GBFV was greater in obese subjects than in nonobese controls (27.5 ± 10.7 vs 11.7 ± 6 ml; P < 0.05). GBRV and GB emptying curves were similar in both groups and did not change during weight loss. The obese subject who developed gallstones (1/10) was the only one who had cholesterol crystals in bile and a sluggish initial GB emptying. In conclusion: (1) obese subjects had a greater GBFV than controls; however, the GB emptying was adequate. (2) During weight loss we did not observe significant changes in GB kinetics or the bile parameters studied. (3) We observed a relatively low frequency of gallstone formation, which can be explained by a high fat content of the diet (26 g/day) and by the adequate GB emptying of our group of patients. (4) An abnormal GB contractility and cholesterol crystals in bile could be considered premonitory to gallstone formation.     

Effects of somatostatin on gallbladder emptying

Because approximately 80% of reported patients with somatostatinomas have gallstones, this study was performed to determine the effects of exogenous somatostatin on gallbladder emptying responses to liquid and solid meals, direct cholinergic stimulation by bethanechol, indirect cholinergic stimulation by sham feeding, and intravenously administered octapeptide of cholecystokinin. Gallbladder emptying was quantitated using 99mTc-HIDA and a gamma-camera on line to a digital computer. Somatostatin, administered at a dosage of 7 micrograms/kg X h, prevented the gallbladder emptying responses to both test meals, sham feeding, and bethanechol. The maximal gallbladder emptying response to octapeptide of cholecystokinin at 5.0 ng/kg X min was reduced from 93.2% +/- 4.8% to 57.1% +/- 9.9% (p less than 0.01) and to octapeptide of cholecystokinin at 0.5 ng/kg X min from 91.3% +/- 5.3% to 14.8% +/- 4.2% (p less than 0.01). These findings suggest that somatostatin is a potent inhibitor of gallbladder emptying in humans. This may be an important factor in the development of gallstones in patients with somatostatinomas.