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PubMed1993

Gallbladder dynamics in chronic pancreatitis. Relationship to exocrine pancreatic function, CCK, and PP release.

Gallbladder dynamics, cholecystokinin (CCK), and pancreatic polypeptide (PP) release were studied in 14 patients with chronic pancreatitis (CP) (2 females, 12 males; age range 24-56 years) and 12 control subjects (4 females, 8 males, 21-50 years). On day 1, gallbladder contractility was investigated after ceruletide intravenous infusion (2.5 ng/kg/min for 10 min). On day 2, a mixed standard test meal (1450 kJ) was administered orally. Gallbladder volume was assessed at three time intervals before (-30, -15, 0 min) and at 5, 10, 20, 30, 40, 50, 60, 80, 100 and 120 min after stimulation by means of ultrasonography. CCK and PP plasma levels were determined at each time interval. Exocrine pancreatic function was assessed using the pancreolauryl serum test (PLT). Six patients with CP had severe exocrine pancreatic insufficiency (EPI) (PLT < 1.8 micrograms/ml) with steatorrhea, eight patients had mild-moderate EPI. Fasting gallbladder volume was increased in CP (32.3 +/- 3.1 cm3) as compared to controls (20.5 +/- 1.2 cm3) (P < 0.01). Peak gallbladder contraction (percent of initial volume) in CP ranged from 5 to 55% (controls: 8-46%) following ceruletide and from 17 to 86% (controls: 27-80%) following the test meal (NS). There was no correlation between the degree of EPI according to PLT and peak gallbladder contraction. Gallbladder emptying in CP patients was not different from controls, although the postprandial CCK response was significantly impaired (P < 0.01). Postprandial PP response in CP was correlated with the PLT result (r = 0.78; P < 0.01) but not with gallbladder emptying or refilling time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Role of nutrient fat and cholecystokinin in regulation of gallbladder emptying in man.

Postprandial gallbladder contraction is mainly regulated by cholecystokinin (CCK), but little is known about the dose-response relationship between CCK release and gallbladder contraction, in particular after meals with differing fat content. Decreased postprandial gallbladder emptying has been suggested to play a major role in the development of gallstones in man, and dietary factors may therefore be important in the pathogenesis of gallbladder stasis. We studied, in a randomized order, the effect of three isocaloric meals (250 ml) with identical osmolality on CCK release and gallbladder contraction in six healthy volunteers: (1) a pure fat meal (25 g triglycerides); (2) a mixed meal containing fat (8 g, 29% of caloric content), protein (10 g, 17%), and dextrose (32 g, 54%); and (3) a fat-free meal containing albumin (25 g, 46%) and dextrose (32 g, 54%). Gallbladder volumes and antral cross-sectional areas were determined by ultrasonography and plasma CCK and PP levels by RIA. The pure fat meal caused the highest CCK release (187 +/- 27; mean +/- SEM) and maximal (> 85% of fasting volume) gallbladder contraction (3172 +/- 361; AUC) as compared to the other two meals (P < 0.05). The mixed and the fat-free meal caused similarly low (< 50% of fasting volume) gallbladder contraction (6052 +/- 342 and 6134 +/- 500, respectively), although they induced markedly different CCK levels (157 +/- 12 and 87 +/- 13, respectively; P < 0.05). Gastric emptying rates were similar for all meals (18,500 +/- 3300, 18,600 +/- 2700 and 19,800 +/- 3100, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Evaluation of gallbladder function before and after gastrectomy using a double-isotope method.

The motor function of the gallbladder after partial distal gastrectomy for gastric carcinoma (Billroth-I reconstruction) and its relationship to the motor function of the stomach was investigated using a double-isotope method. In this method, [99mTc]N-54-pyridoxyl-5-methyltryptophan ([99mTc]PMT) was utilized as a tracer for the biliary tract and [111In]diethyl-triaminopontacetic acid ([111In]DTPA) mixed with a liquid test meal was used as a tracer for the digestive tract. Gastric emptying half-time (GET1/2) was measured, since this was used historically as the physiologic indicator of gallbladder contractile stimulus. The volume of test meal that emptied from the stomach into the duodenum per minute (VOL/MIN) was measured, as was the gastric emptying duration (GED). A series of gallbladder emptying phenomena were analyzed using three different criteria: gallbladder emptying half-time (GBET1/2), retention rate of bile in the gallbladder (RR), and the start of gallbladder bile ejection into the duodenum after ingestion (TL: time lag). While GET1/2 was reduced (P < 0.01) and VOL/MIN was increased (P < 0.01) after gastrectomy, GED was shortened remarkably (P < 0.01). GBET1/2 showed no significant change, RR increased (P < 0.05), and TL was prolonged (P < 0.01). The postoperative dysfunction of the gallbladder was caused by the short and intense stimulus on the biliary tract during the duodenal phase and by intraoperative injury to the innervation of the gallbladder. In particular, the hepatic branch of the left vagus nerve was injured during the right paracardiac lymph node dissection performed as a component of the radical gastrectomy.

Adult↗

PubMed1996

Effects of intravenous infusion of amino acids on cholecystokinin release and gallbladder contraction in humans.

We investigated the effect of intravenous infusions of the therapeutically available amino acid solutions Moripron and Morihepamin (Roussel Morishita, Osaka, Japan) on gallbladder contraction and cholecystokinin (CCK) release in healthy male volunteers. Plasma CCK levels were measured by radioimmunoassay, using the antibody OAL-656, which is specific for the aminoterminus of CCK-8 and thus recognizes biologically active forms of all CCKs. The volume of the gallbladder was calculated by ultrasonographic measurements. Intravenous infusion of Moripron at the rate of 3.33 ml/min for 60 min, caused gallbladder contraction, with a peak response of 31.3 +/- 8.6% of the fasting volume at 45-60 min, and a significant increase in plasma CCK concentration, from 1.8 +/- 0.2 pmol/l to a peak of 9.9 +/- 1.5 pmol/l, at 30-45 min. The maximum gallbladder contraction and the peak CCK release during the Moripron infusion were not significantly different from findings after a test meal. There was a close relationship between the peak plasma CCK concentration and the maximal gallbladder contraction during the administration of Moripron, and this agent, even when infused at the rate of 1.67 ml/min, significantly increased plasma CCK levels and gallbladder contraction. Intravenous infusion of Morihepamin had no significant influence on gallbladder volume or plasma CCK levels. The discrepancy in responses appeared to be related to differences in composition between Moripron and Morihepamin, and not to the total dose of amino acid. Intravenous infusions of amino acids appear to have different effects on gallbladder contraction and plasma CCK secretion depending on the amino acids composition. Our findings suggest that an intravenous infusion of Moripron could be used for the prophylaxis of acute acalculous cholecystitis and sludge formation due to reduced biliary motility in patients on total parenteral nutrition.

Adult↗

PubMed2002

Radical second resection provides survival benefit for patients with T2 gallbladder carcinoma first discovered after laparoscopic cholecystectomy.

Port site recurrence or peritoneal seeding is a fatal complication following laparoscopic cholecystectomy for gallbladder carcinoma. The aims of this retrospective analysis were to determine the association of gallbladder perforation during laparoscopic cholecystectomy with port site/peritoneal recurrence and to determine the role of radical second resection in the management of gallbladder carcinoma first diagnosed after laparoscopic cholecystectomy. A total of 28 patients undergoing laparoscopic cholecystectomy for gallbladder carcinoma were analyzed, of whom 10 had a radical second resection. Five patients had recurrences; port site/peritoneum recurrence in 3 and distant metastasis in 2. The incidence of port site/peritoneal recurrence was higher in patients with gallbladder perforation (3/7, 43%) than in those without (0/21, 0%) (p = 0.011). The outcome after laparoscopic cholecystectomy was worse in 7 patients with gallbladder perforation (cumulative 5-year survival of 43%) than in those without (cumulative 5-year survival of 100%) (p <0.001). Among 13 patients with a pT2 tumor, the outcome after radical second resection (cumulative 5-year survival of 100%) was better than that after laparoscopic cholecystectomy alone (cumulative 5-year survival of 50%) (p = 0.039), although there was no survival benefit of radical second resection in the 15 patients with a pT1 tumor (p = 0.65). In conclusion, gallbladder perforation during laparoscopic cholecystectomy is associated with port site/peritoneal recurrence and worse patient survival. Radical second resection may be beneficial for patients with pT2 gallbladder carcinoma first discovered after laparoscopic cholecystectomy.

Adenocarcinoma↗

PubMed1992

Opposite effects of cholestyramine and loxiglumide on gallbladder dynamics in humans.

The aim of this study was to conduct dose-response studies of the effect of cholestyramine, alone or in combination with a test meal, on gallbladder emptying studied by ultrasonography in 31 healthy volunteers. The role of cholecystokinin in mediating the effects of cholestyramine was studied using the cholecystokinin-receptor antagonist loxiglumide. In the absence of a test meal, cholestyramine produced a dose-dependent decrease in gallbladder volume; minimal residual volumes were 30% (2 g), 55% (4 g), and 110% (12 g) of the minimal volume produced by a test meal alone. Gallbladder volume was still only 50% of the initial volume, 24 hours after ingestion of 12 g cholestyramine. Cholestyramine also enhanced gallbladder emptying in response to the test meal (n = 7). Oral loxiglumide strongly inhibited gallbladder evacuation in response to either test meal (n = 6) or cholestyramine alone (n = 6) but partially blocked gallbladder emptying when the resin was added to the test meal (n = 12). It is concluded that (a) cholestyramine alone or in combination with a test meal produces a marked decrease in gallbladder volume and (b) the action of the resin itself on gallbladder motor function appears to be mainly, but not solely, mediated by cholecystokinin through the disinhibition of the luminal feedback mechanism between bile salts and the endogenous release of cholecystokinin.

Adult↗

PubMed1994

Contractile mechanisms of gallbladder filling and emptying in dogs.

BACKGROUND/AIMS: The mechanisms of gallbladder filling and emptying during the fasting state, postprandial state, and after intravenous administration of cholecystokinin, motilin, and morphine were investigated in conscious dogs. METHODS: Bile flow in the cystic and common bile ducts was measured by miniature flow probes. RESULTS: The gallbladder showed brief alternating excursions of filling and emptying in the fasting and fed state. The emptying excursions exceeded the filling excursions during phase II and for about 4 hours after a meal. The filling excursions exceeded the emptying excursions during phase I, phase III, and the latter half of the postprandial state. Most gallbladder emptying occurred when its pressure was high, and most filling occurred when its pressure was low. The duodenal contractions played a major role in gallbladder filling and emptying during phase III. CONCLUSIONS: Gallbladder filling and emptying are not monotonous during the fasting and postprandial states. The brief alternating excursions of filling and emptying would almost continually mix the concentrated gallbladder bile with the fresh dilute hepatic bile to prevent supersaturation of the gallbladder bile during the fasting state and extend the delivery of a small volume of concentrated gallbladder bile for a period of several hours after a meal.

Animals↗

PubMed1997

Two cases of torsion of the gallbladder diagnosed preoperatively.

BACKGROUND: The authors experienced two cases of torsion of the gallbladder, both of which were correctly diagnosed preoperatively. METHODS: Two boys, aged 4 and 5 years, were transferred to Yokohama City Seibu Hospital because of their acute abdominal disorders. Diagnostic imaging demonstrated acute inflammatory changes in the gallbladder with an abnormal arrangement of the gallbladder and common bile duct in both cases. Laparotomy findings showed torsion of the gallbladder by 180 degrees and 360 degrees, respectively, at the cystic ducts, resulting in gangrenous change. RESULTS: Both children recovered uneventfully after cholecystectomy. The diagnostic imaging criteria are (1) collection of fluid between the gallbladder and the gallbladder fossa of the liver, (2) a horizontal rather than vertical arrangement of the long axis of the gallbladder, (3) the presence of a well-enhanced cystic duct located on the right side of the gallbladder, and (4) signs of inflammation including marked edema with thickening of the wall. CONCLUSIONS: The authors report the clinical characteristics of this uncommon condition, and discuss the significance of accurate preoperative diagnosis of these acute surgical disorders.

Child, Preschool↗

PubMed1984

Gallbladder disease and cholecystectomy rate are independently variable.

In Britain, gallstones can be expected to develop in 1 in 3 women and 1 in 5 men. Gallbladder disease in Dundee was more frequent in 1974-83 than in 1953-73. During 1961-81 the number of cholecystectomies trebled in Dundee and doubled in Scotland as a whole, but this could not be explained by changes in the prevalence of gallbladder disease. Between 1974 and 1983 in Dundee, 48 patients died of gallstone disease. 22 out of 54 (41%) patients with common bileduct stones at necropsy and 26 out of 1034 (2.5%) with gallbladder stones only at necropsy died from an associated cause. A further 26 died from gallbladder surgery without bileduct surgery. Gallbladder disease was not associated with death from myocardial infarction, and there was no relationship between gallstones and gallbladder cholesterolosis. 22 patients were found to have secondary carcinoma of the gallbladder and 17 were found to have primary carcinoma of the gallbladder at necropsy.

Adolescent↗

PubMed1998

Effect of insulin on basal and cholecystokinin-stimulated gallbladder motility in humans.

BACKGROUND/AIMS: Acute hyperglycemia inhibits gallbladder contraction. In non-diabetic subjects this inhibitory effect may result from endogenous hyperinsulinemia. Therefore we investigated the effects of acute hyperglycemia and euglycemic hyperinsulinemia on basal and cholecystokinin-stimulated gallbladder motility. METHODS: Gallbladder volume (ultrasonography) and duodenal bilirubin output were studied simultaneously in nine healthy volunteers (age 20-52 years) on 3 separate occasions in random order during: (a) saline infusion (control), (b) hyperglycemic hyperinsulinemic clamping (HG; plasma glucose at 15 mmol/l), and (c) euglycemic hyperinsulinemic clamping (HI; plasma insulin at 150 mU/l, glucose at 4-5 mmol/l). After a 2-h basal clamp period, cholecystokinin was infused intravenously for 60 min at 0.25 IDU x kg(-1) x h(-1), followed by another 60 min at 0.5 IDU x kg(-1) x h(-1). RESULTS: HI and HG significantly (p<0.05) reduced basal duodenal bilirubin output compared to control, while basal gallbladder volume did not change. At the low dose cholecystokinin, gallbladder emptying during HG (25+/-3%) and HI (39+/-4%) was significantly (p<0.01) reduced compared to control (61+/-4%). The inhibitory effect of HG was significantly (p<0.05) stronger compared to HI. Duodenal bilirubin output during the low dose cholecystokinin was significantly (p<0.05) reduced by HG, but not by HI. No inhibitory effect of HG and HI on gallbladder emptying and duodenal bilirubin output was observed with the high dose of cholecystokinin. CONCLUSIONS: In healthy subjects acute hyperglycemia and euglycemic hyperinsulinemia reduce basal duodenal bilirubin output and inhibit gallbladder emptying stimulated by low dose cholecystokinin. These results suggest that insulin is involved in the inhibitory effect of hyperglycemia on basal and cholecystokinin-stimulated gallbladder motility.

Adult↗

PubMed1997

Ras p21 protein immunoreactivity and its relationship to p53 expression and prognosis in gallbladder and extrahepatic biliary carcinoma.

Ras oncogene mutation is found in many human malignancies. The ras family of genes consists of three functional genes which encode highly similar, guanine nucleotide-binding, proteins (p21) of 21kDa, with GTPase activity. The p21 protein is present on the inner aspect of the plasma membrane of a variety of cells. Using a polyclonal antibody, pan-ras p21 (Oncogene Science), the immunohistochemical expression of the ras oncogene in human gallbladder adenocarcinoma (n = 13) and dysplasia (n = 3), chronic cholecystitis (n = 11), common bile duct carcinoma (n = 6), together with ampullary carcinoma (n = 8) and carcinoma in situ (CIS) (n = 3), was examined. A statistically significant difference in ras p21 immunoreactivity between gallbladder cancers and chronic cholecystitis (P = 0.032; chi 2 test) was demonstrated. Strong ras p21 immunoreactivity was present in most gallbladder carcinomas (n = 8; 62%) but not in the cases of gallbladder dysplasia (n = 1; 33%) or chronic cholecystitis (n = 2; 18%). However, the ras p21 expression was strong in only a minority of the cases of ampullary carcinoma (n = 1; 13%), common bile duct carcinomas (n = 3; 50%), and none of the ampullary CIS, and was not shown to be statistically significant. There was no statistically significant correlation between ras p21 expression and patient survival (r = 0.18, r2 = 0.031, P = 0.56; simple regression analysis), or between ras p21 expression and p53 immunoreactivity (r = 0.13, r2 = 0.017, P = 0.47; simple regression analysis). In conclusion, ras p21 expression is increased in most cases of gallbladder carcinomas with no specific relationship to tumour grade suggesting that it may be important in the development of gallbladder carcinomas but not in its progression. No significant correlation was found between ras p21 expression and p53 immunoreactivity in gallbladder and biliary tract tumours and ras p21 immunoreactivity does not appear to be of any prognostic value. The lower rate of ras p21 overexpression in common bile duct and ampullary carcinomas suggests that these tumours may have a different molecular origin to gallbladder cancers.

Adenocarcinoma↗

PubMedDate not supplied

Inflammatory cytokines alter human gallbladder epithelial cell absorption/secretion.

Gallbladder inflammation is an early feature of gallstone formation in animal models. The inflammatory response is associated with increases in myeloperoxidase and interleukin (IL)-1 activities in the gallbladder wall. The present studies were designed to determine whether inflammatory cytokines directly affect gallbladder epithelial cell absorptive function. Studies were performed using cultured human gallbladder epithelial cells derived from a well-differentiated gallbladder carcinoma. Confluent monolayers were exposed to interleukin-1 (IL-1alpha), IL-1alpha plus its specific receptor inhibitor IL-1ra, tumor necrosis factor (TNF-alpha), lipopolysaccharide, or prostaglandin E2. Unidirectional sodium and chloride fluxes were measured and used to calculate net ion fluxes. Compared to control monolayers, lipopolysaccharide, prostaglandin E2, IL-1alpha, and TNF-alpha decreased mucosal-to-serosal and net sodium and chloride fluxes and increased serosal-to-mucosal movement of sodium and unmeasured ions. The effects of IL-1alpha were completely inhibited by its specific receptor antagonist IL-1ra. Similar to the proinflammatory agents lipopolysaccharide and prostaglandin E2, the inflammatory cytokines IL-1alpha and TNF-alpha directly affected gallbladder epithelial cell absorptive function. Because normal gallbladder absorptive function is protective against gallstone formation, alterations in absorptive function due to inflammation in the gallbladder wall may play a role in gallstone pathogenesis.

Absorption↗

PubMed2003

Methods of measuring gallbladder motor functions--the need for standardization: scintigraphy.

Emptying the gallbladder is part of the complex process of food digestion. The gallbladder interacts with other gastrointestinal organs and its movements are coordinated and modified by functions of the stomach, intestine and pancreas. Many factors can modify gallbladder motility, for example, sex and age of the subject, their body mass, the kinds of food ingested and stimulus used. The assumption that the gallbladder progressively empties during meals and refills during fasting is incorrect. Using a combination of ultrasonography and cholescintigraphy, it is possible to measure absolute and net gallbladder emptying. In this way we demonstrated that the gallbladder begins to refill immediately after emptying begins, and the difference between net and absolute emptying of the gallbladder indicates the refilling of bile and provides a measure of bile turnover rate, an accurate index to assess gallbladder motility.

Cholecystokinin↗

PubMed2004

Determinants of gallbladder kinetics in obesity.

Obese subjects are at risk of developing gallstones both by being overweight and by reducing their body weight. The aim of the present study was to investigate factors related to disturbances in gallbladder emptying measured by ultrasound. Detailed information about weight loss attempts, age at onset of obesity, parity, presence of menopause, use of contraceptive or hormonal replacement drugs, and phase of menstrual cycle was obtained. Smoking habits, alcohol use, dietary intake, and physical activity were recorded. Body composition and fat distribution were assessed by anthropometry. Blood samples were taken for CCK, lipids, glucose, and insulin. Mean (SD) fasting gallbladder volume was 30.0 (12.6) ml. The residual volume was 12.5 (9.8) ml 90 min after a test meal. CCK levels increased from a basal 1.64 (0.8) pM to a peak value of 2.9 (1.0) pM. Fasting gallbladder volumes were closely related to residual and ejection volumes. Body weight and fasting insulin levels explained 35.2% of the variance in fasting volume, lean body mass and insulin explained 28.1% of the residual volume, and waist circumference 23.6% of the ejection volume. None of the other factors were related to gallbladder emptying. Subjects with the largest fasting gallbladders had the largest residual and least emptying gallbladders, scored the highest in every aspect of body size, composition, and fat distribution, and also had the highest insulin levels. Body weight, lean body mass, central fat distribution, and insulin levels were the main determinants of gallbladder kinetics. Fasting and residual gallbladder volumes were closely related and both determined by obesity and its metabolic complication of hyperinsulinemia.

Adipose Tissue↗

PubMed2004

Subcellular localization of the ABCG2 transporter in normal and malignant human gallbladder epithelium.

Epithelium of the gallbladder and biliary tract is exposed to high concentrations of potentially harmful exogenous and endogenous compounds excreted into primary bile. As the ATP-dependent efflux pump ABCG2 can prevent cellular accumulation of anticancer drugs, estrogen sulfate, xenobiotics, porphyrins, and sterols, its expression in the biliary tract might mediate protection by hindering their penetration. We therefore investigated the expression and subcellular distribution of ABCG2 in normal and malignant human gallbladder. After demonstrating ABCG2 expression in gallbladder epithelium by RT-PCR and Western blotting, we analyzed the subcellular localization of ABCG2 by indirect immunofluorescence in gallbladder adenocarcinoma specimens, and compared it to that in cholelithiasis, and normal gallbladder samples (n = 54). In control, cholelithiasis, and well-differentiated tumor samples (grade 1, T1-3), ABCG2 is present at the luminal membrane of epithelial cells, which was proven by colocalization of apical-bound TRITC-labeled lectin (wheat germ agglutinin). In poorly differentiated gallbladder adenocarcinomas, intracellular ABCG2, in addition to luminal ABCG2 immunoreactivity, was found in 13/21 carcinoma samples (grade 2 and 3, T2-4, P < 0.01). In 3/11 of grade 3 tumors, ABCG2 was present in the cytoplasmatic compartment only (P < 0.01). In proliferating bile ducts of cholangiocarcinomas, ABCG2 showed an analogous staining pattern with presence in cytosolic compartments. However, the apical marker enzyme neutral endopeptidase remained on the membrane in all samples. To study whether phosphatidylinositol 3-kinase (PI3K) signaling might be necessary for ABCG2 membrane insertion, we treated freshly isolated human gallbladder epithelial cells with the PI3K inhibitor wortmannin. As assessed by indirect immunofluorescence, this maneuver redistributes ABCG2 to intracellular compartments. In conclusion, our data suggest a protective role for ABCG2 in well-differentiated gallbladder epithelial cells. Cytoplasmatic accumulation of ABCG2 in poorly differentiated carcinomas might coincide with malfunctioning of PI3K-signaling pathways during tumor progression.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2003

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.

Age Factors↗

PubMed2006

Effect of sildenafil citrate on postprandial gallbladder motility.

OBJECTIVE: Sildenafil stimulates the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway through inhibition of type 5 phosphodiesterase. NO-cGMP pathway causes smooth muscle relaxation. The aim of this study is to evaluate the effects of sildenafil on gallbladder motility. METHODS: Twenty healthy male volunteers (21-35 years old) participated in this randomized, double blind, crossover, and placebo-controlled study. Oral sildenafil (50 mg) or placebo was randomly dispensed to each volunteer on two consecutive days. After the sildenafil or placebo, a special meal with a high fat content was administered. Gallbladder volume was measured using sonography preprandially and at 5, 15, 30, 60, 120 and 180 minutes postprandially. RESULTS: Sildenafil showed an inhibitory effect on gallbladder contraction in healthy volunteers that began at 30 minutes. Gallbladder volumes showed significant differences at 30 minutes following the test meal (approximately 50-60 min after the sildenafil intake), between placebo (15.4 +/- 5.1 mL) and the sildenafil groups (19.3 +/- 6.1 mL) (P < 0.05). In addition, gallbladder volume was significantly higher during the refilling phase in the sildenafil group (P < 0.05 at 180 min). Maximal contraction was achieved at 60 minutes in each group. CONCLUSIONS: Sildenafil constituted a significant inhibitory effect on gallbladder discharge in healthy individuals when compared with placebo group. Because of this inhibitory effect, sildenafil consumption for long periods may potentiate risks of gallbladder disorders and gallstone formation resulting from disturbed gallbladder motility.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2000

The effect of acute oral erythromycin on gallbladder motility and on upper gastrointestinal symptoms in gastrectomized patients with and without gallstones: a randomized, placebo-controlled ultrasonographic study.

OBJECTIVE: Gastrectomy might be a risk factor for cholelithiasis and gallbladder stasis might play a major role. We studied fasting and postprandial gallbladder motility with 600 mg oral erythromycin or placebo in gastrectomized patients (with and without gallstones) and controls. METHODS: Seventeen patients operated on for gastric cancer (subtotal gastrectomy: n = 10, total gastrectomy: n = 7) were compared with 20 sex- and body-size matched healthy controls. Subjects randomly received erythromycin or placebo 30 min before the ingestion of a standard 200 ml liquid test meal. Gallbladder volume was estimated by ultrasonography until 120 min after test meal. A visual analog scale monitored GI perception of appetite, satiety, nausea, abdominal fullness and epigastric pain. RESULTS: Gastrectomized patients had increased fasting gallbladder volume (35.9 +/- 3.4 ml versus 21.0 +/- 1.4 ml, p = 0.0005) with faster postmeal emptying (T/2 14.8 +/- 1.1 min versus 23.5 +/- 1.5 min, p = 0.00019) than controls. Six patients developed small and asymptomatic gallstones, which did not influence gallbladder motility. In these patients, fasting gallbladder volume increased with time after surgery (r = +0.82, p = 0.047). Perception of satiety, abdominal fullness, and epigastric pain after ingestion of the test meal were all significantly greater in patients than in controls. Erythromycin significantly enhanced gallbladder emptying during fasting (p = 0.001) and postprandially in both patients and controls (0.002 < p < 0.017) and significantly reduced postmeal satiety and epigastric discomfort in gastrectomized patients. CONCLUSIONS: Increased fasting volume might be a form of stasis, predisposing patients to gallstone formation. Erythromycin improves fasting and postprandial gallbladder emptying and decreases upper GI symptoms in gastrectomized patients.

Administration, Oral↗