Gallbladder Refilling Research Articles

Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility.

Liraglutide treatment is associated with gallbladder-related disorders and has been shown to delay postprandial gallbladder refilling. The gut hormones cholecystokinin (CCK), fibroblast growth factor 19 (FGF19) and glucagon-like peptide 2 (GLP-2), are known to regulate gallbladder motility and may be implicated in gallbladder-related disorders associated with liraglutide treatment. In a double-blind, 12-week trial, 52 participants [50% male, age 47.6 ± 10.0 years, body mass index 32.6 ± 3.4kg/m2 (mean ± standard deviation)] with obesity were randomized 1:1 to once-daily subcutaneous liraglutide (escalated from 0.6mg to 3.0mg once-daily) or placebo. During liquid meal tests performed at baseline, after the first dose and following 12 weeks of treatment, we evaluated postprandial gallbladder dynamics and plasma responses of CCK, FGF19 and GLP-2. Liraglutide reduced postprandial FGF19 after the first dose [area under the curve (AUC)0-240 min 24.8 vs. 48.0min× ng/ml, treatment ratio (TR) (95% confidence interval) 0.52 (0.39; 0.69)] and following 12 weeks of treatment [AUC0-240 min 33.7 vs. 48.5ng/ml × min, TR 0.69 (0.52; 0.93)]. Liraglutide also reduced postprandial GLP-2 responses (AUC0-240 min 3650 vs. 4894 min× pmol/L, TR 0.75 (0.62; 0.90)] following the first dose as well as after 12 weeks [AUC0-240 min 3760 vs. 4882 min× pmol/L, TR 0.77 (0.60; 0.99)]. Liraglutide increased postprandial responses of CCK after the first dose [AUC0-240 min 762 vs. 670 min× pmol/L; TR 1.14 (0.97; 1.33)] and following 12 weeks of treatment [AUC0-240 min 873 vs. 628 min× pmol/L; TR 1.39 (1.12; 1.73)]. Compared with placebo, treatment with liraglutide decreased postprandial FGF19 and GLP-2 concentrations and increased postprandial CCK concentrations, which may explain the delayed postprandial gallbladder refilling observed in individuals with obesity treated with liraglutide.

1982-P: Glucagon-Like Peptide-2 Inhibits Postprandial Gallbladder Emptying in Healthy Male Individuals—A Randomized, Double-Blinded, Placebo-Controlled Study

A recent study in mice has demonstrated that the gut-derived hormone glucagon-like peptide-2 (GLP-2) may be involved in the regulation of gallbladder motility and induces gallbladder refilling. This study evaluated the effect of exogenous GLP-2 on postprandial gallbladder motility in humans. On three experimental days, 15 young healthy males ([mean±SEM] age 24.3±1.9 years, BMI 22.5±0.9 kg×m-2, HbA1c 4.8±0.1% (29.3±1.5 mmol/mol)) were subjected to a 3.5-hour 300 kcal mixed liquid meal-test. Continuous 4-hour intravenous infusions of placebo (saline), low-dose GLP-2 (1 pmol×kg-1×min-1) or high-dose GLP-2 (10 pmol×kg-1×min-1) were initiated 30 min before meal ingestion. Gallbladder volume was determined by ultrasonography, and gallbladder ejection fraction was calculated. Postprandial maximum gallbladder ejection fraction during saline infusion (76.3±2.8%) was significantly reduced by low-dose GLP-2 (65.5±3.5%, P=0.026) and completely abolished during high-dose GLP-2 infusion (4.0±3.7%, P<0.0001) (Figure). Postprandial peak plasma glucose was lower during high-dose GLP-2 infusion (6.4±0.2 mmol/l) compared to low-dose GLP-2 (6.9±0.2mmol/l, P=0.0004) and placebo infusion (7.2±0.2 mmol/l, P=0.008). In conclusion, exogenous GLP-2 dose-dependently inhibits postprandial gallbladder emptying in healthy male subjects. Disclosure N.L. Hansen: None. C.C. Nexøe-Larsen: None. A. Brønden: Other Relationship; Self; AstraZeneca. A.S. Christensen: None. D.P. Sonne: None. B. Hartmann: None. T. Vilsbøll: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S.

New Avenues in the Regulation of Gallbladder Motility—Implications for the Use of Glucagon-Like Peptide–Derived Drugs

Several cases of cholelithiasis and cholecystitis have been reported in patients treated with glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) and GLP-2 receptor agonists (GLP-2RAs), respectively. Thus, the effects of GLP-1 and GLP-2 on gallbladder motility have been investigated. We have provided an overview of the mechanisms regulating gallbladder motility and highlight novel findings on the effects of bile acids and glucagon-like peptides on gallbladder motility. The articles included in the present review were identified using electronic literature searches. The search results were narrowed to data reporting the effects of bile acids and GLPs on gallbladder motility. Bile acids negate the effect of postprandial cholecystokinin-mediated gallbladder contraction. Two bile acid receptors seem to be involved in this feedback mechanism, the transmembrane Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor. Furthermore, activation of TGR5 in enteroendocrine L cells leads to release of GLP-1 and, possibly, GLP-2. Recent findings have pointed to the existence of a bile acid-TGR5-L cell-GLP-2 axis that serves to terminate meal-induced gallbladder contraction and thereby initiate gallbladder refilling. GLP-2 might play a dominant role in this axis by directly relaxing the gallbladder. Moreover, recent findings have suggested GLP-1RA treatment prolongs the refilling phase of the gallbladder. GLP-2 receptor activation in rodents acutely increases the volume of the gallbladder, which might explain the risk of gallbladder diseases associated with GLP-2RA treatment observed in humans. GLP-1RA-induced prolongation of human gallbladder refilling may explain the gallbladder events observed in GLP-1RA clinical trials.

Effect of cholecystectomy on bile acid synthesis and circulating levels of fibroblast growth factor 19

Background and rationale for the study. FGF19/15 is a gut-derived hormone presumably governing bile acid (BA) synthesis and gallbladder (GB) refilling. FGF19 mRNA is present in human GB cholangiocytes (hGBECs); however, the physiological significance of GB-derived FGF19 remains unknown. We investigated whether hGBECs secrete FGF19 and the effects of cholecystectomy on serum FGF19 ([FGF19]s) and BA synthesis.Material and methods. FGF19 expression was assessed by qRT-PCRs and immunostaining in hGBECs and terminal ileum, and quantified in bile and serum by ELISA. Basal and BA (chenodexycholic acid, CDCA) induced FGF19 expression and secretion was analyzed in primary cultured hGBECs and GB-d1 cell line. Pre and postprandial serum changes in [FGF19]s, 7α-hydroxy-4-cholestene-3-one (C4, a marker of BA synthesis) and BA were evaluated in plasma of gallstone disease patients at baseline and after cholecystectomy.Results. FGF19 mRNA levels were -250-fold higher in hGBECs compared to distal ileum. GB bile contained -23-fold higher FGF19 levels compared to serum (p < 0.0001). CDCA induced dose-dependent expression and secretion of FGF19 in hGBECs and GB-d1 cells. Cholecystectomy increased plasma BA synthesis ≥ 2-fold (p < 0.0001), and altered the diurnal rhythm and significantly reduced [FGF19]s noon peak. BA serum levels, serum cholesterol and triglyceride content remained unchanged.Conclusions. In conclusion human GB cholangiocytes constitutively express and secrete high levels of FGF19 in a process regulated by BA. Resection of this organ doubles BA synthesis concomitantly with changes in [FGF19]s. These findings suggest a potential connection between GB cholangiocytes-derived FGF19 and BA metabolism that could lead to metabolic dysregulation following cholecystectomy.

Non-Newtonian flow of pathological bile in the biliary system: experimental investigation and CFD simulations

The paper presents an experimental study of pathological human bile taken from the gallbladder and bile ducts. The flow dependences were obtained for different types of bile from patients with the same pathology, but of different age and sex. The parameters of the Casson’s and Carreau’s equations were found for bile samples. Results on the hysteretic bile behavior at loading-unloading tests are also presented, which proved that the pathologic bile is a non-Newtonian thixotropic liquid. The viscosity of the gallbladder bile was shown to be higher compared to the duct bile. It was found that at higher shear stress the pathological bile behaves like Newtonian fluid, which is explained by reorientation of structural components. Moreover, some pathological bile flow in the biliary system CFD simulations were performed. The velocity and pressure distributions as well as flow rates in the biliary segments during the gallbladder refilling and emptying phases are obtained. The results of CFD simulations can be used for surgeons to assess the patient’s condition and choose an adequate treatment.

Pharmacological Activation of the Bile Acid Nuclear Farnesoid X Receptor Is Feasible in Patients with Quiescent Crohn's Colitis

BackgroundThe bile acid-activated nuclear receptor Farnesoid X Receptor (FXR) is critical in maintaining intestinal barrier integrity and preventing bacterial overgrowth. Patients with Crohn's colitis (CC) exhibit reduced ileal FXR target gene expression. FXR agonists have been shown to ameliorate inflammation in murine colitis models. We here explore the feasibility of pharmacological FXR activation in CC.MethodsNine patients with quiescent CC and 12 disease controls were treated with the FXR ligand chenodeoxycholic acid (CDCA; 15 mg/kg/day) for 8 days. Ileal FXR activation was assessed in the fasting state during 6 hrs after the first CDCA dose and on day 8, by quantification of serum levels of fibroblast growth factor (FGF) 19. Since FGF19 induces gallbladder (GB) refilling in murine models, we also determined concurrent GB volumes by ultrasound. On day 8 ileal and cecal biopsies were obtained and FXR target gene expression was determined.ResultsAt baseline, FGF19 levels were not different between CC and disease controls. After the first CDCA dose, there were progressive increases of FGF19 levels and GB volumes during the next 6 hours in CC patients and disease controls (FGF19: 576 resp. 537% of basal; GB volumes: 190 resp. 178% of basal) without differences between both groups, and a further increase at day 8. In comparison with a separate untreated control group, CDCA affected FXR target gene expression in both CC and disease controls, without differences between both groups.ConclusionsPharmacological activation of FXR is feasible in patients with CC. These data provide a rationale to explore the anti-inflammatory properties of pharmacological activation of FXR in these patients.Trial RegistrationTrialRegister.nl NTR2009

Quantitative cholescintigraphy with fatty meal in the diagnosis of Sphincter of Oddi dysfunction and acalculous cholecystopathy

To evaluate the role of quantitative cholescintigraphy with fatty meal in the management of biliary dyskinesia and to describe the findings according to Sostre score (SS) criteria in patients with gallbladder (GB) in-situ and biliary pain. We performed a retrospective analysis of the hepatobiliary (HIDA) studies (n = 35) performed for evaluation of biliary dyskinesia either due to biliary pain, opioid induced sphincter of Oddi dysfunction (SOD), recurrent pancreatitis (RP) or post cholecystectomy syndrome (PCS). Gallbladder ejection fraction (GBEF) was calculated from the post fatty meal HIDA images (excluding PCS patients). Studies with GBEF ≤40 % and SS >4 were considered to have cholecystopathy and SOD respectively. Three of the 13 patients with PCS had SS of 6 each, suggestive of SOD. Delayed biliary visualization (>15 min) and activity in common bile duct 60 min > liver 15 min were the specific features in these cases. Opioid induced SOD patients had SS >4 with retrograde refilling of GB in one patient and normalization of the SS parameters after nifedipine challenge in the other patient. Patients with RP and biliary pain were stratified into four groups, normal (GBEF >40 % and SS ≤4), cholecystopathy (GBEF ≤40 % and SS ≤4), normal with SOD (GBEF >40 % and SS >4) and cholecystopathy with SOD (GBEF ≤40 % and SS >4). Four patients with intact GB had cholecystopathy with scintigraphic features of SOD. Quantitative cholescintigraphy with fatty meal and SS scoring identified biliary dyskinesia and SOD in patients with biliary pain, recurrent pancreatitis and post-cholecystectomy syndrome.

Variabilities of gallbladder contraction indices and a simple regression model for gallbladder and gastric emptying ratio

The objective of this study was to assess the variabilities of gallbladder contraction indices (GBCI) and derive a predictive model for gallbladder and gastric motility. The gallbladder volume and gastric antral measurements were obtained from 24 healthy male volunteers in preprandial and post-milk ingestion states. After preprandial measurement of the gallbladder volume and gastric antral area, each subject ingested 157 ml of full cream milk and 30 cl of ion-free water. In supine position, the gallbladder volume and the gastric antral area were obtained every five minutes for 40 minutes. For the gallbladder while only the 5(th), 10(th) and 15(th) measurement of gastric antral area were obtained. Gallbladder contraction indices were calculated and gastric emptying ratio obtained at the fifteenth minute is the indication of gastric motility. Statistical analyses were conducted using SPSS version 16.0 with p < 0.05 as criterion of statistical significance. The GBCIs followed Gaussian response at some stages and did not at some other stages. The least variability occurred at the 35th measurement of GBCI. A cut- off value for the 35th minute GBCI value was established with the mean ± 2 SD (80.79 ± 11.5%). Obvious gallbladder refilling was noted after 35 minutes. A positive relationship was noted between gallbladder and gastric motilities. With milk dilution, the variability of gall bladder motility is least at the 35th minute. A significant positive relationship between gastric emptying and gallbladder contraction index was also observed.

Rapid Postprandial Gallbladder Refilling and Increased Turnover of Bile Prevent Cholesterol Crystallization in Small Heterodimer Partner (SHP) Knockout Mice

Rapid Postprandial Gallbladder Refilling and Increased Turnover of Bile Prevent Cholesterol Crystallization in Small Heterodimer Partner (SHP) Knockout Mice

Gallbladder Motor Function in Patients with Different Thyroid Hormone Status

Hypothyroidism and hyperthyroidism are known to affect cholesterol metabolism, bile acid synthesis and bile content. There are previous studies reporting increased prevalence of gallstone and common bile duct stone formation in hypothyroidism. The aim of this study was to compare gallbladder (GB) motor function between euthyroid, hypothyroid and hyperthyroid subjects by conventional ultrasonography. Eighteen euthyroid, 14 hypothyroid and 20 hyperthyroid, age, sex and body mass index matched subjects were included in the study. Etiology of hypothyroidism comprised of thyroidectomy, Hashimoto's thyroiditis and previous radioactive iodine therapy. Hyperthyroid group included patients with toxic nodular goitre and Graves' disease. Patients who have diseases or are under drug treatment known to affect biliary function were not included in the study. Fasting and post-stimulus GB volumes were measured by real-time conventional ultrasonography and computer unit (Aloka UST-979, 3.5 mHz electronic convex probe, Japan). No significant differences were noted for fasting, post-stimulus GB volumes and GB ejection fraction between euthyroid, hypothyroid and hyperthyroid subjects. Measuring GB motility accurately is not straightforward because besides being not static during fasting, after a meal, intermittent emptying and refilling of GB occurs. Ultrasonography is affected by GB filling and measures "net" GB emptying. Although cumbersome, additional evaluation with cholescintigraphy which detects "absolute" GB emptying and is not affected by GB filling may provide complete assessment of motor function and may be more informative in evaluating subjects with different thyroid hormone status.

Acute effect of smoking on gallbladder emptying and refilling in chronic smokers and nonsmokers: A sonographic study

To ultrasonographically evaluate the acute effects of smoking on gallbladder contraction and refilling in chronic smokers and nonsmokers. Fifteen chronic smokers (21-30 years old) and fifteen nonsmokers (21-35 years old) participated in this study. Chronic smokers were selected among the volunteers who had been smoking for at least 5 years and 10 cigarettes per day (mean 17.5/d). Examinations were performed in two separate days. In the first day, basal gallbladder (GB) volumes of volunteers were measured after 8-h fasting. After the examinations, participants had a meal containing at least 30-40 gram fat. Gallbladder volume was assessed at 5, 15, 30, 60, 120 and 180 min after the meal. In the second day, participants smoked 2 cigarettes after 8-h fasting. Then, they had the same meal, and gallbladder measurements were repeated at the same time points. Same procedures were applied to both groups. The mean starving GB volumes were 23.3 +/- 3.3 mL in the first day, 21.9 +/- 3.0 mL in the second day in nonsmoker group and 18.3 +/- 3.0 mL in the first day, 19.5 +/- 2.8 mL in second day in smoker group. There was no significant difference between starving GB volumes. We did not find any significant difference between the GB volumes measured at 5, 15, 30, 60, 120 and 180 min in the first and second days in nonsmoker group. In smokers, post cigarette GB volume was found significantly higher at 5, 15 and 30 min which corresponded to GB contraction phase (P < 0.05). Control GB volume measurements were not significantly different between the two groups. Post-smoking GB volumes were also not significantly different between the two groups. Smoking prolongs the maximal GB emptying time both in smokers and in nonsmokers though it is not significant. It delays GB contraction in chronic smokers and causes a significant decrease in GB emptying volume. Smoking causes no significant delay in GB refilling in both smokers and nonsmokers. These effects of smoking observed in acute phase result in bile stasis in GB. Bile stasis is the underlying cause of most GB disorders in chronic process.

Ultrasonography in the assessment of gallbladder motor activity.

Ultrasonography is an accurate and useful method for studying gallbladder volume variations and thus indirectly gallbladder emptying and refilling in humans. It has been shown that gallbladder main motor function is the result of a bellows-like mechanism with outflow and inflow of bile occurring during continuously alternating phases of gallbladder emptying and filling, that in turn lead to bile recycling within the gallbladder. Therefore, bile flux through the gallbladder cannot be properly expressed by time and rate of gallbladder emptying and gallbladder ejection fraction. In an attempt to analyse the gallbladder volume-hepatic bile flux relationship, simultaneous assessment of the gallbladder volume variations at ultrasonography and of the labelled bile in the gallbladder at cholescintigraphy during continuous infusion of an hydroxy iminodiacetic acid compound has been carried out. By applying a mathematical model to the analysis of gallbladder volume ultrasonography measurements, it is possible to measure the flux of bile through the gallbladder. By validating ultrasonography assessment of gallbladder volume variations with quantitative cholescintigraphy, it has been shown that the single non-invasive ultrasonography technique with serial frequent measurements of the gallbladder volume enables separate estimation of the flux of bile through the gallbladder in humans and in physiological conditions. In the postprandial state, hepatic bile was mainly: (1) stored in the gallbladder in a first phase; (2) emptied from the gallbladder in a second phase; and (3) stored in the gallbladder in a third phase. The amount of bile flowing bidirectionally through the cystic duct was about fivefold greater than that estimated with the usually employed variables, such as gallbladder ejection fraction or emptying and refilling delta volume. The mathematical analysis of minute-by-minute ultrasonography measurements of gallbladder volume variations yields both physiological and pathological insights. In healthy volunteers, it has been shown that: (1) caloric content of meals affects the total amount of bile recycled by the gallbladder; and (2) fat content of meals affects the modality of gallbladder emptying and refilling but does not affect the total amount of bile recycled by the gallbladder. In gallstone patients, a decreased turnover of bile has been shown which may contribute to cholesterol crystal precipitation and stone growth. In conclusion, unlike conventional variables used to assess gallbladder motor function such as gallbladder ejection fraction and rate of gallbladder emptying, mathematical analysis of frequent ultrasonography measurements of gallbladder volume variations enables non-invasive estimation of bile flow through the gallbladder in normal and abnormal physiological conditions.

Oral clarithromycin enhances gallbladder emptying induced by a mixed meal in healthy subjects

Background: In humans, erythromycin has been demonstrated to accelerate gallbladder emptying due to its motilin-like effects on the gastrointestinal tract. Recently, it was shown that clarithromycin, another macrolide, used for the eradication of Helicobacter pylori infection, also stimulated gastrointestinal motility in the fasting state. We conducted a comparative study on the effects of a single oral dose of clarithromycin and of erythromycin on gallbladder emptying in healthy subjects. Methods: Gallbladder emptying variables (residual volume, ejection fraction, area under emptying curve) were measured by ultrasound in 21 healthy subjects (11 males, 10 females, mean age 42.5±10.6 years). A test meal (14 g fat, 425 kcal) was ingested 30 min after a single oral dose (500 mg) of either clarithromycin or erythromycin, and the measurements were repeated the following day with the other drug (cross-over double-blind study). A control group consisting of 12 subjects (seven males, five females, mean age 50.7±8.2 years) was used to evaluate gallbladder emptying following the same test meal without drug administration. Differences between groups were analyzed using two-tailed Student’s t-test for unpaired observations. Results: Gallbladder emptying at 60, 75, and 90 min was greater after erythromycin ( P<0.05 at 90 min) and clarithromycin than it was in controls. The ejection fraction was significantly greater after clarithromycin (76.5%) and erythromycin (79.7%) than it was in controls. Gallbladder refilling occurred earlier after clarithromycin than after erythromycin. Conclusions: The prokinetic effect of clarithromycin on the gallbladder appears to be of similar amplitude but of shorter duration than that of erythromycin.

The chronopharmacological effect of curcumin on human gall-bladder

Human gallbladder physiologically contracts and relaxes periodically. It has been demonstrated that curcumin (C) an active compound of Curcuma xanthorrhiza and Curcuma domestica produces a positive cholekinetic effect. The objective of this study is to define the influence of physiologic contraction and refilling of human gallbladder on the cholekinetic effect of Curcumin, and to determine the rime to achieve the maximum gall-bladder contraction after administration of 40 mg curcumin. Twelve healthy volunteers ingested 40 mg C and placebo (P) in a randomized double blind cross over study design. The volumes of gallbladder before and after taking C and P were half hourly determined by utrasonography and calculated using the ellipsoid methad for 6.0 hours. After P administration there is no gallbladder contraction. While afier C administration there was a contraction phase for 2 hours followed by a refilling phase for another 2.5 hours and then followed by second gall-bladder contraction started for 4.5 up to 6.0 hours. The maximal volume of gallblndder after 6.A hours was less than the basal volume, The cholekinetic effect of C is not chronopharmacologically influenced by the gall-bladder physiologic periodic contraction and refilling. The maximum contraction effect of C was achieved at 2 hours after oral administraion. (Med J Indones 2001; 10: 219-23)

Mechanisms of cisapride affecting gallbladder motility.

Regulation of gallbladder motility is complex. Mechanisms via which cisapride may interact with gallbladder function are being reviewed. These are multiple and include direct effects on gallbladder and the sphincter of oddi, as well as indirect effects involving gastro-intestinal hormone levels, gastric emptying, gallbladder refilling, interdigestive migrating motor cycle (IMMC) and small intestinal transit. Effects, moreover, may vary according to dose, route and duration of cisapride administration, which may explain conflicting data so far with cisapride.

Effect of cisapride on gallbladder motility after extracorporeal shock-wave lithotripsy

Background/Aims: Altered gallbladder motility is regarded as one of the important factors involved in the formation and recurrence of gallstones. Previous studies have suggested that cisapride increases post-prandial gallbladder contraction and may therefore be theoretically useful in preventing stone recurrence. The aim of our study was therefore to investigate the effect of cisapride on gallbladder motility in stone-free patients after extracorporeal shock-wave lithotripsy, as compared to healthy volunteers pair-matched for age and sex.Methods: Each subject received cisapride or placebo in a double-blind, cross-over, random order. Gallbladder volumes were measured by ultrasomography in the fasting state and after intake of a standard liquid meal. Plasma cholecystokinin levels were determined by radioimmunoassay.Results: Fasting gallbladder volumes were smaller in patients as compared to volunteers (20.7±1.3 ml vs. 46.0±9.2 ml; p<0.05) but were not modified by cisapride (21.1±1.7 ml vs. 58.6±11.3 ml). The maximal postprandial decrease in gallbladder volume was similar in patients and volunteers (64.5±12% vs. 62±10%; NS) and was not significantly altered by cisapride (59±9.4% vs. 54±9%; NS). In patients, cisapride increased integrated postprandial gallbladder volume by accelerating gallbladder refilling as compared to placebo by 37±15% (p<0.05). Integrated cholecystokinin plasma levels were similar in patients and volunteers and were 13.4±4.7% higher after cisapride as compared to placebo (p<0.05).Conclusions: The results of this study suggest that cisapride does not alter postprandial gallbladder contraction but accelerates gallbladder refilling in patients free from gallstones after extracorporeal shock-wave lithotripsy. This effect of cisapride is probably due to an acceleration of gastric emptying also causing a secondary enhanced cholecystokinin release.

Effect of gastrectomy on gallbladder motility: an experimental study

Gallstone formation is frequently seen following gastric surgery. Since dysmotility and bile stasis of the gallbladder is considered as an important factor in the pathogenesis of gallstone formation, altered gallbladder motility due to gastric surgery may have a role in the development of post-gastrectomy gallstone formation. To test this hypothesis, the effect of distal partial gastrectomy on gallbladder motility were studied. Gastroduodenal and gallbladder contractions were recorded by chronically implanted strain gauge transducers under conscious state. Gallbladder volume changes were monitored using chronically indwelling gallbladder catheter. Fasted and fed motility were studied in control (n = 5) and gastrectomized (n = 3) dogs. Plasma concentration of putative hormone CCK was measured. Effect of CCK-OP and motilin on gallbladder emptying were also studied. In fasted state, gallbladder volume was periodically decreased synchronous with phase 3 of interdigestive migrating contractions (IMC) in the gastroduodenum in both group of dogs. The correlation between gastric and gallbladder contractions was preserved even following distal partial gastrectomy, though the frequency of phasic contractions during phase 3 of IMC was decreased in the gastrectomized dogs. Postprandial gallbladder emptying tend to decreased in the gastrectomized dogs, while there were no difference in the postprandial plasma CCK concentrations and CCK-OP induced gallbladder emptying between groups. Digestive period was shortened in the gastrectomized dogs, which resulted in early gallbladder refilling and prolonged interdigestive period. Decreased frequency of gallbladder phasic contractions during IMC and prolonged interdigestive period could cause bile stasis in the gallbladder, which may, in part, explain post-gastrectomy gallbladder formation.

Coordination of gastric and gallbladder emptying after ingestion of a regular meal

The relationship of gallbladder emptying and refilling to gastric emptying of solids, gastrointestinal transit time, and human pancreatic polypeptide response was examined after ingestion of a standard breakfast (40% fat) in 12 healthy men and women. Gallbladder volume, emptying, and refilling was measured by real-time ultrasonography, and gastric emptying of solids was measured scintigraphically by the disappearance from the stomach of egg labeled with 99mTc-sulfur colloid. Gastrointestinal transit time was defined as the time of initial rise in breath hydrogen following ingestion of 10 g of lactulose. Serum human pancreatic polypeptide level was measured by radioimmunoassay. Gallbladder emptying was biphasic, initially 0.015 ± 0.003 min−1 and later 0.005 ± 0.001 min−1, and gallbladder volume remained small until refilling began at 249 ± 67 min. Gallbladder refilling was 70% complete at 335 ± 57 min. The slower rate of gallbladder emptying and tonic gallbladder contraction occurred during gastric emptying of solids. Gallbladder refilling began when ∼13% of solids remained in the stomach. Serum human pancreatic polypeptide showed the expected biphasic response to the meal and returned to basal levels at approximately the time of initiation of gallbladder refilling. The gastrointestinal transit time of women was twice that of men (73.6 ± 20.2 vs. 37.5 ± 22.7, p = 0.025). No other sex-related differences were detected. We conclude that gastric emptying of the solid portion of a meal containing fat maintains tonic gallbladder contraction through continued release of humoral mediators from small bowel and pancreas. When gastric emptying nears completion, humoral stimulation ceases and the gallbladder refills. Human pancreatic polypeptide does not appear to be responsible for gallbladder refilling.

Gallbladder and small intestinal regulation of biliary lipid secretion during intraduodenal infusion of standard stimuli.

The gallbladder and small intestine are reservoirs for the bile acid pool during its enterohepatic circulation and, as such, may regulate biliary secretion of bile acid. During studies of biliary bile acid secretion, a stimulus to gallbladder contraction is continuously infused into the duodenum. Under these conditions, it is assumed that the gallbladder is tonically contracted and that the rate of bile acid secretion into the duodenum equals the hepatic bile acid secretion rate. However, secretion rates vary by as much as 100%, depending upon which of two standard stimuli is used. Therefore, we studied the role of gallbladder emptying and small intestinal transit in determining biliary lipid secretion rate and composition during infusion of these stimuli in five healthy subjects. Each subject was studied with a liquid formula containing 40% of calories as fat, and with an amino acid solution for 10 h. Bile acid, phospholipid, cholesterol, and markers were measured in duodenal bile and hourly secretion rates were calculated by marker dilution technique. Real-time gallbladder sonographs and serum pancreatic polypeptide levels were obtained every 30 min. Small bowel transit time was estimated levels were obtained every 30 min. Small bowel transit time was estimated by the breath hydrogen response after giving lactulose intraduodenally.During liquid formula infusion, gallbladder emptying was more complete, small intestinal transit was faster, and pancreatic polypeptide levels were higher. Secretion rates of all lipids were greater and molar percent cholesterol was lower. For the combined data from both infusions, the secretory relationships of cholesterol to bile acid, cholesterol to phospholipid, and phospholipid to bile acid were curvilinear. We conclude that more complete gallbladder emptying and faster intestinal transit increase the enterohepatic cycling of bile acids and lower the molar percent cholesterol of bile. Some of the fluctuation observed in biliary lipid secretion rates, especially during amino acid infusion, is due to gallbladder refilling and emptying.