Stimulation Of Gallbladder Contraction Research Articles

The gallbladder in diabetes

The gallbladder in diabetes

Optimal hepatobiliary scintigraphy for gallbladder dyskinesia

BackgroundThe accuracy of hepatobiliary scintigraphy to assess gallbladder function remains controversial. National supply shortages of pharmaceutical-grade cholecystokinin led to the use of an oral fatty meal to stimulate gallbladder contraction during hepatobiliary scintigraphy. The goal of this study was to compare the predictive indices of cholecystokinin and fatty meal ingestion for stimulation of gallbladder contraction. MethodsPatients evaluated with hepatobiliary iminodiacetic acid scan from 2014 to 2017 were reviewed and grouped based on testing stimulant (fatty meal versus cholecystokinin). Patients who later underwent cholecystectomy were selected for analysis. Hepatobiliary iminodiacetic acid results were correlated with surgical pathology and postoperative resolution of symptoms. Two-way statistical analysis was performed. ResultsA total of 359 patients underwent hepatobiliary iminodiacetic acid scan followed by cholecystectomy for biliary dyskinesia. Patients who received fatty meal stimulant (n = 86) were compared to those that received cholecystokinin (n = 273). Mean gallbladder ejection fraction during hepatobiliary iminodiacetic acid was 38% and 44% for the cholecystokinin and fatty meal groups, respectively, P = .073. Predictive metrics were not statistically different between groups with regard to pathology, symptomatic improvement, or accuracy. Symptomatic resolution (cholecystokinin–hepatobiliary iminodiacetic acid 78%, fatty meal–hepatobiliary iminodiacetic acid 68%; P = 0.058) and specificity (cholecystokinin–hepatobiliary iminodiacetic acid 26%, fatty meal–hepatobiliary iminodiacetic acid 44%, P = 0.417) were comparable in both testing groups. ConclusionStimulation of gallbladder contraction with a fatty meal during hepatobiliary iminodiacetic acid testing is a more affordable and reliable alternative to cholecystokinin for patients undergoing evaluation for gallbladder dysmotility.

The unappreciated roles of the cholecystokinin receptor CCK(1) in brain functioning.

The CCK(1) receptor is a G-protein-coupled receptor activated by the sulfated forms of cholecystokinin (CCK), a gastrin-like peptide released in the gastrointestinal tract and mammal brain. A substantial body of research supports the hypothesis that CCK(1)r stimulates gallbladder contraction and pancreatic secretion in the gut, as well as satiety in brain. However, this receptor may also fulfill relevant roles in behavior, thanks to its widespread distribution in the brain. The strategic location of CCK(1)r in mesolimbic structures and specific hypothalamic and brainstem nuclei lead to complex interactions with neurotransmitters like dopamine, serotonin, and glutamate, as well as hypothalamic hormones and neuropeptides. The activity of CCK(1)r maintains adequate levels of dopamine and regulates the activity of serotonin neurons of raphe nuclei, which makes CCK(1)r an interesting therapeutic target for the development of adjuvant treatments for schizophrenia, drug addiction, and mood disorders. Unexplored functions of CCK(1)r, like the transmission of interoceptive sensitivity in addition to the regulation of hypothalamic hormones and neurotransmitters affecting emotional states, well-being, and attachment behaviors, may open exciting roads of research. The absence of specific ligands for the CCK(1) receptor has complicated the study of its distribution in brain so that research about its impact on behavior has been published sporadically over the last 30 years. The present review reunites all this body of evidence in a comprehensive way to summarize our knowledge about the actual role of CCK in the neurobiology of mental illness.

Liquid gastric emptying as an adjunct to hepatobiliary scintigraphy when oral corn oil is used as a cholecystagogue for determining gallbladder emptying.

During times of sincalide shortage, a fatty meal can be used to stimulate gallbladder contraction during hepatobiliary scintigraphy. However, if a patient has an abnormal gallbladder ejection fraction (GBEF), is the cause chronic cholecystitis or is it inadequate cholecystokinin stimulation due to poor gastric emptying? Hence, during the 2014 sincalide shortage, simultaneous liquid gastric emptying using (99m)Tc-sulfur colloid along with corn oil emulsion was initiated as routine practice in patients evaluated for GBEF. The objective of this study was to retrospectively assess the time course of gastric emptying in these patients, especially with regard to whether delayed gastric emptying may be a factor in some patients with a poor GBEF. My institution's clinical imaging procedure during the 2014 sincalide shortage consisted of routine (99m)Tc-mebrofenin hepatobiliary scintigraphy followed by corn oil emulsion and (99m)Tc-sulfur colloid orally. Dynamic imaging with regions of interest encompassing the gallbladder and the stomach allowed determination of GBEF and gastric emptying. For this study, the imaging records for 53 consecutive patients undergoing this clinical procedure were reviewed. The time for half gastric emptying, along with percentage gastric emptying at the end of imaging, was evaluated in relationship to GBEF. Seventeen patients had a normal GBEF (74% ± 14%) and satisfactory gastric emptying (31 ± 21 min for half emptying, 75% ± 14% emptying at end of imaging); 17 patients had a normal GBEF (77% ± 17%) despite unsatisfactory gastric emptying (only 30% ± 14% emptying at end of imaging); 5 patients had an abnormal GBEF (19% ± 9%) and satisfactory gastric emptying (26 ± 19 min for half emptying, 82% ± 14% emptying at end of imaging), supporting a diagnosis of chronic cholecystitis; 11 patients had an abnormal GBEF (26% ± 9%) but also unsatisfactory gastric emptying (only 26% ± 13% emptying at end of imaging), which did offer additional support for a diagnosis of chronic cholecystitis; and 3 patients had a borderline GBEF (40% ± 2%) with satisfactory gastric emptying (59% ± 6% emptying at end of imaging). Simultaneous liquid gastric emptying can provide additional information in the interpretation of GBEF when a fatty meal is used as an oral cholecystagogue, especially to help differentiate chronic cholecystitis from inadequate cholecystokinin stimulation due to poor gastric emptying.

Cholecystokinin-Assisted Hydrodissection of the Gallbladder Fossa during FDG PET/CT-guided Liver Ablation

A 68-year-old female with colorectal cancer developed a metachronous isolated fluorodeoxyglucose-avid (FDG-avid) segment 5/6 gallbladder fossa hepatic lesion and was referred for percutaneous ablation. Pre-procedure computed tomography (CT) images demonstrated a distended gallbladder abutting the segment 5/6 hepatic metastasis. In order to perform ablation with clear margins and avoid direct puncture and aspiration of the gallbladder, cholecystokinin was administered intravenously to stimulate gallbladder contraction before hydrodissection. Subsequently, the lesion was ablated successfully with sufficient margins, of greater than 1.0 cm, using microwave with ultrasound and FDG PET/CT guidance. The patient tolerated the procedure very well and was discharged home the next day.

Cholagogue-induced gallbladder emptying in the diagnosis of canine biliary obstruction

The efficacy of ultrasound-guided cholagogue-induced gallbladder emptying for differentiating obstructive from non-obstructive hepatobiliary diseases was studied in icteric dogs. In 7 healthy Beagle dogs, Lipofundin 20% infusion (2 ml/kg orally) evoked a vigorous gallbladder contraction of 44.2% (range: 35.3-57.6%) and proved to be a useful, well-tolerable meal for routine use. In 24 icteric dogs, gallbladder contraction was evoked by different cholagogues: the maximum reduction in gallbladder volume (%) for the three non-obstructive icteric dogs was 43.9% (range, 39.0-46.5%). The average gallbladder contraction of the 21 dogs with biliary obstruction was less than 5%. In conclusion, the stimulation of gallbladder contraction with orally applied magnesium sulphate (MgSO4) or Lipofundin can be well demonstrated by ultrasound in dogs. The examination of cholagogue-induced gallbladder emptying is a valuable technique in icteric patients to indicate surgical intervention.

Therapeutic potential for novel drugs targeting the type 1 cholecystokinin receptor

Cholecystokinin (CCK) is a physiologically important gastrointestinal and neuronal peptide hormone, with roles in stimulating gallbladder contraction, pancreatic secretion, gastrointestinal motility and satiety. CCK exerts its effects via interactions with two structurally related class I guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs), the CCK(1) receptor and the CCK(2) receptor. Here, we focus on the CCK(1) receptor, with particular relevance to the broad spectrum of signalling initiated by activation with the natural full agonist peptide ligand, CCK. Distinct ligand-binding pockets have been defined for the natural peptide ligand and for some non-peptidyl small molecule ligands. While many CCK(1) receptor ligands have been developed and have had their pharmacology well described, their clinical potential has not yet been fully explored. The case is built for the potential importance of developing more selective partial agonists and allosteric modulators of this receptor that could have important roles in the treatment of common clinical syndromes.

Duodenal phytohaemagglutinin (red kidney bean lectin) stimulates gallbladder contraction in humans

Lectins, carbohydrate-specific proteins without enzymatic activity on the ligand, are daily ingested plant proteins which survive the passage through the gastrointestinal tract in a biologically active form. Their binding to glycan determinants of natural glycoconjugates can trigger biological effects. The lectin phytohaemagglutinin (PHA) is abundantly present in red kidney beans and induces cholecystokinin (CCK) release in rats. The aim of the study was to investigate the effect of intraduodenal administration of PHA on plasma CCK levels and gallbladder contraction in humans and to elucidate potential mechanisms of action. Five healthy volunteers underwent four studies. After a basal intraduodenal saline infusion for 30 min, PHA or heat-inactivated PHA was infused in increasing doses: 150 microg, 1.5 mg and 15 mg for 30 min each. Intravenous saline, CCK(1) receptor antagonist dexloxiglumide or atropine were administered in random order. Gallbladder volumes were measured by ultrasonography and plasma CCK levels by radioimmunoassay. Intraduodenal PHA induced gallbladder contraction in a dose-dependent fashion starting with the lowest dose. The highest dose reduced the gallbladder volume to 65.3 +/- 9.4% of basal volume (P < 0.001) whereas heat-inactivated PHA did not have any effect. Blocking CCK(1) or muscarinic receptors completely abolished PHA-stimulated gallbladder contraction (dexloxiglumide 208.7 +/- 23.7%; atropine 104 +/- 7.0% of basal volume) while none of the treatments affected CCK levels. Duodenal administration of PHA potently stimulates gallbladder contraction in humans. This contraction is mediated via cholinergic pathway.

Low Dose Lipid Formulations: Effects on Gastric Emptying and Biliary Secretion

Food stimulates changes to gastrointestinal secretion and motility patterns, however, the effect of smaller quantities of lipid, such as that contained in a lipid-based drug formulation, has not been detailed. This study aimed to examine the effects of small quantities of lipid on gastric emptying and biliary secretion. The influence of oral administration of three lipid-based formulations and a negative control formulation on gastric emptying and biliary secretion was evaluated in 16 healthy male subjects using gamma scintigraphy, ultrasonography and duodenal aspiration. Low quantities (2 g) of long chain lipid stimulated gall bladder contraction and elevated intestinal bile salt, phospholipid and cholesterol levels. Changes in gastric emptying were also evident, although these did not reach statistical significance. Administration of a similar quantity of medium chain lipid, however, had little effect on gastric emptying and gallbladder contraction and did not stimulate appreciable increases in intestinal concentrations of biliary-derived lipids. The quantities of long chain lipid that might be administered in a pharmaceutical formulation stimulate gallbladder contraction and elevate intestinal levels of bile salt and phospholipid. This effect is a likely contributor to the ability of lipid based formulations to enhance the absorption of poorly water-soluble drugs.

Ultrasonographic evaluation of fatty meal stimulated gallbladder contraction in the diagnosis of biliary dyskinesia in children

Abstract Aim: Biliary dyskinesia (BD) is characterized by symptoms of biliary disease, no evidence of gallstones on ultrasonography (USG), and diminished gallbladder ejection fraction. The diagnosis is based on findings of abnormal gallbladder ejection fraction diagnosed by hepatobiliary scintigraphy before and after stimulation of gallbladder contraction with cholecystokinin (CCK). We used an easier diagnostic technique defined as ultrasonographic evaluation of fatty meal stimulated gallbladder contraction, employing USG with the diagnosis of biliary dyskinesia in children. The study was conducted by USG to investigate the volume and contractility of the gallbladder (GB) in fasting conditions and 45 min after a standardized fatty meal (SFM) in normal children and in a group of BD patients, and to compare the diagnostic value of this test with scintigraphy and to evaluate its use as a new method in the diagnostic algorithm of BD. Methods: We assessed the volume changes and contractility of the GB in response to SFM by USG in 14 patients with BD diagnosed by cholecystokinin stimulated hepatobiliary scintigraphy (CCKs‐HBS); and compared them with 14 control patients matched for age and gender before cholecystectomy. After an overnight fasting, GB volume was measured by USG then the GB volume was again measured after the SFM ingestion. Using USG, length, width and height of GB were measured, and volume of the GB was calculated using the ‘Dodds’ formula. These volume measurements were used to calculate the percentage of gallbladder emptying (ejection fraction). Fasting, after SFM and EF values comparisons between groups were done with student's t‐test. Results: No statistically significant difference of fasting GB volumes were demonstrated between BD and control groups (14.1±6.7 cm3 and 13.4±4.0 cm3 respectively). GB volumes of the BD group after SFM were significantly greater than in healthy controls (13.1±1.8 cm3 and 3.4±0.9 cm3 respectively, P&lt;0.0005). The calculated percentage of gallbladder contraction (ejection fraction) was found to be lower in BD patients than in healthy controls (7.1%±1.8% and 73.8%±6.4%, respectively, P&lt;0.0005). Conclusion: Ultrasonographic evaluation of fatty meal stimulated gallbladder contraction provides relatively reliable and reproducible results. Thus it can be used for scanning in patients with biliary symptoms as a prior modality to CCK‐HBS since it is a relatively easier, safer and available method with which to make a definitive diagnosis of BD. The patients with symptoms of biliary disease and no evidence of gallstones on USG should be evaluated by the method proposed in this study before the routine laboratory and radiologic tests.

Ultrasonographic evaluation of fatty meal stimulated gallbladder contraction in the diagnosis of biliary dyskinesia in children

Biliary dyskinesia (BD) is characterized by symptoms of biliary disease, no evidence of gallstones on ultrasonography (USG), and diminished gallbladder ejection fraction. The diagnosis is based on findings of abnormal gallbladder ejection fraction diagnosed by hepatobiliary scintigraphy before and after stimulation of gallbladder contraction with cholecystokinin (CCK). We used an easier diagnostic technique defined as ultrasonographic evaluation of fatty meal stimulated gallbladder contraction, employing USG with the diagnosis of biliary dyskinesia in children. The study was conducted by USG to investigate the volume and contractility of the gallbladder (GB) in fasting conditions and 45 min after a standardized fatty meal (SFM) in normal children and in a group of BD patients, and to compare the diagnostic value of this test with scintigraphy and to evaluate its use as a new method in the diagnostic algorithm of BD. We assessed the volume changes and contractility of the GB in response to SFM by USG in 14 patients with BD diagnosed by cholecystokinin stimulated hepatobiliary scintigraphy (CCKs-HBS); and compared them with 14 control patients matched for age and gender before cholecystectomy. After an overnight fasting, GB volume was measured by USG then the GB volume was again measured after the SFM ingestion. Using USG, length, width and height of GB were measured, and volume of the GB was calculated using the 'Dodds' formula. These volume measurements were used to calculate the percentage of gallbladder emptying (ejection fraction). Fasting, after SFM and EF values comparisons between groups were done with student's t-test. No statistically significant difference of fasting GB volumes were demonstrated between BD and control groups (14.1+/-6.7 cm3 and 13.4+/-4.0 cm3 respectively). GB volumes of the BD group after SFM were significantly greater than in healthy controls (13.1+/-1.8 cm3 and 3.4+/-0.9 cm3 respectively, P<0.0005). The calculated percentage of gallbladder contraction (ejection fraction) was found to be lower in BD patients than in healthy controls (7.1%+/-1.8% and 73.8%+/-6.4%, respectively, P<0.0005). Ultrasonographic evaluation of fatty meal stimulated gallbladder contraction provides relatively reliable and reproducible results. Thus it can be used for scanning in patients with biliary symptoms as a prior modality to CCK-HBS since it is a relatively easier, safer and available method with which to make a definitive diagnosis of BD. The patients with symptoms of biliary disease and no evidence of gallstones on USG should be evaluated by the method proposed in this study before the routine laboratory and radiologic tests.

Fat in the intestine as a regulator of appetite—role of CCK

The present review summarizes the appetite-suppressing effects of intestinal fat in the regulation of food intake in humans, with a special focus on the role of cholecystokinin (CCK). Current evidence supports a role for intestinal fat (especially long-chain free fatty acids) acting via the peptide CCK as a physiological satiety pathway. The regulation of satiety is, however, complex and it is not surprising that multiple control systems exist. It is interesting to note that nutrients, such as hydrolysis products of fat in the small intestine, stimulate the release of satiety peptides, such as CCK or PYY, that serve as satiety signals. CCK, released from the gastrointestinal tract by the local action of digested food, exerts various functions: stimulation of gallbladder contraction and exocrine pancreatic secretion, inhibition of gastric emptying, and inhibition of appetite. CCK functions therefore (1) as a positive feedback signal to stimulate digestive processes and (2) as negative feedback signal to limit the amount of food consumed during an individual meal.

Factors affecting gallbladder motility: drugs.

Various drugs and medications that inhibit or stimulate gallbladder contraction and basal tone in humans are described. Active gallbladder contraction may be achieved using synthetic hormones such as cholecystokinin, caerulein and motilin, cholinomimetic drugs such as bethanecol, prostigmine, and erythromycin due to its motilin-like effect. Furthermore, cisapride and cholestyramine, may have some excitatory activity on the gallbladder muscle. Intravenous amino acids also induce gallbladder contraction through the release of cholecystokinin. Inhibition of gallbladder contraction induced by a meal, or reduction of the basal fasting tone may be achieved by using atropine and other cholinergics, and by inhibitory hormones such as somatostatin, the nitric acid releaser arginine, the calcium channel antagonist nifedipine, and progesterone. Other drugs such as trimebutine, loperamide and ondansetron may negatively affect gallbladder contraction.

Review article: gall-bladder motility after intestinal surgery.

There is a close relationship in humans between gall-bladder motility and gastrointestinal motility during the fasting state, as well as in the post-prandial period. Only a minority of publications take this relationship into account in the description of biliary dysmotility after various surgical procedures. Most publications deal with post-prandial gall-bladder motility or with stimulation of gall-bladder contraction from various prokinetic drugs or gastrointestinal hormones. Impaired gall-bladder motility has been demonstrated after Billroth II gastric resection, pyloroplasty and colectomy, but the epidemiological data on the risk of gallstone formation in these patients are too scarce and equivocal to recommend prophylactic cholecystectomy. Future studies on gall-bladder motility after surgical procedures should include measurements of gall-bladder motility during the fasting state, as well as in the post-prandial period. The measurements should be related to the migrating motor complexes, and this necessitates a simultaneous recording of gastrointestinal motility.

Stimulated gastrointestinal hormone release and gallbladder contraction during continuous jejunal feeding in patients with pancreatic pseudocyst is inhibited by octreotide.

Continuous enteral feeding, the old-new therapeutic modality in the treatment of patients with acute pancreatitis and those with complications is considered to bypass the cephalic, the gastric, and (at least in part) the intestinal phase of pancreatic secretion. The aim of this study was to test the GI hormonal changes and gallbladder motility during CJF in patients with pancreatic pseudocysts following acute pancreatitis, with or without octreotide pretreatment. In 15 patients with pancreatic pseudocysts, an 8-French (8F) nasojejunal catheter was positioned into the jejunum distal to the ligament of Treitz during duodenoscopy. On test d 1, blood samples were taken for CCK, gastrin, insulin-like immunoreactivity (IRI), glucagon, and glucose measurements prior to and at 20, 40, 60, and 120 min following jejunal saline infusion at a rate of 2 mL/min. The gallbladder volumes were determined simultaneously by ultrasonography. On test d 2, CJF (175 kcal/h) was started by the same route and at the same infusion rate. Analogous measurements were performed as indicated above. On test d 3, 100 microg of octreotide was administered subcutaneously and the previous procedure was repeated. The plasma level of CCK and glucagon and the serum levels of IRI and gastrin were determined by bioassay and radioimmunoassay (RIA), respectively. Significant changes in hormone levels were not observed during jejunal saline perfusion. However, the levels of CCK (5.7+/-0.9 pmol), gastrin (10.6+/-1.3 pmol/L), IRI (27.2+/-5.8 microIU/mL), glucagon (322.8+/-32.4 pg/mL), and glucose (5.8+/-1.0 mmol/L) were significantly increased at 20 min during CJF vs the saline controls (2.0+/-0.3 pmol, 6.8+/-1.1 pmol/L, 7.8+/-0.4 microIU/mL, 172.8+/-33.4 pg/mL, and 4.5+/-0.5 mmol/L, respectively) and remained elevated at 40, 60, and 120 min. Octreotide pretreatment eliminated the increases in CCK, gastrin, IRI, and glucagon levels observed during CJF alone. The significant decrease in gallbladder volume during CJF was also prevented by octreotide pretreatment. Continuous jejunal feeding (CJF) elicited significant increases in gastrointestinal (GI) regulatory hormone (cholecystokinin [CCK], gastrin, IRI, and glucagon) levels and evoked a consecutive gallbladder contraction. These biological responses are eliminated by octreotide pretreatment. Further clinical studies are needed to assess the eventual therapeutic effect of octreotide during CJF in patients with pancreatic pseudocyst.

Bolus Intravenous Infusion of Amino Acids or Lipids Does Not Stimulate Gallbladder Contraction in Neonates on Total Parenteral Nutrition

Stimulation of gallbladder contraction in patients receiving total parenteral nutrition (TPN) may be beneficial in preventing cholestatic jaundice associated with TPN. Bolus intravenous administration of either amino acids or fat promotes gallbladder contraction in normal adult volunteers after a period of starvation. This phenomenon has not been investigated in patients receiving continuous TPN. The aim of this study was to test the hypothesis that bolus intravenous infusion of amino acids or fat produces gallbladder contraction in neonates receiving TPN. Methods: Twentyeight studies of gallbladder contraction were performed in 18 neonates receiving continuous TPN (median weight, 2.3 kg; range, 1.3 to 7.3; gestational age, 37 weeks; range, 28 to 40; age, 6.5 days; range, 2 to 180). Different types of experiments were performed: (1) bolus intravenous infusion of amino acid or fat for 60 minutes at twice the normal infusion rate; (2) bolus intravenous infusion of amino acid or fat for 15 minutes at four times the normal infusion rate. Gallbladder volume was measured by real‐time ultrasonography by a single investigator. Measurements were made before starting the bolus infusion and every 15 minutes for 1 hour. Results: The volume of the gallbladder before bolus intravenous infusion was not significantly different between experiments (median, 985; range, 603 to 1,802 mm3). These volumes are consistent with an enlarged and atonic gallbladder as previously reported in infants receiving parenteral nutrition. In all experiments there was no significant decrease in gallbladder volume after bolus infusion of either amino acids or fat. Conclusions: Contrary to their effects in adults, bolus infusions of amino acids or fat did not induce gallbladder contraction in neonates on TPN. This may have been because of lack of starvation in the neonates and/or the effect of continuous glucose infusion.

Coffee and Gastrointestinal Function: Facts and Fiction: A Review

Background: Effects of coffee on the gastrointestinal system have been suggested by patients and the lay press, while doctors tend to discourage its consumption in some diseases. Methods: The literature on the effects of coffee and caffeine on the gastrointestinal system is reviewed with emphasis on gastrointestinal function. Results: Although often mentioned as a cause of dyspeptic symptoms, no association between coffee and dyspepsia is found. Heartburn is the most frequently reported symptom after coffee drinking. It is demonstrated that coffee promotes gastro-oesophageal reflux. Coffee stimulates gastrin release and gastric acid secretion, but studies on the effect on lower oesophageal sphincter pressure yield conflicting results. Coffee also prolongs the adaptive relaxation of the proximal stomach, suggesting that it might slow gastric emptying. However, other studies indicate that coffee does not affect gastric emptying or small bowel transit. Coffee induces cholecystokinin release and gallbladder contraction, which may explain why patients with symptomatic gallstones often avoid drinking coffee. Coffee increases rectosigmoid motor activity within 4 min after ingestion in some people. Its effects on the colon are found to be comparable to those of a 1000 kCal meal. Since coffee contains no calories, and its effects on the gastrointestinal tract cannot be ascribed to its volume load, acidity or osmolality, it must have pharmacological effects. Caffeine cannot solely account for these gastrointestinal effects. Conclusions: Coffee promotes gastro-oesophageal reflux, but is not associated with dyspepsia. Coffee stimulates gallbladder contraction and colonic motor activity.

Bolus intravenous infusion of amino acids or lipids does not stimulate gallbladder contraction in neonates on total parenteral nutrition

Background/Purpose: Stimulation of gallbladder contraction in patients receiving total parenteral nutrition (TPN) may be beneficial in preventing cholestatic jaundice associated with TPN. Bolus intravenous administration of either amino acids or fat promotes gallbladder contraction in normal adult volunteers after a period of starvation. This phenomenon has not been investigated in patients receiving continuous TPN. The aim of this study was to test the hypothesis that bolus intravenous infusion of amino acids or fat produces gallbladder contraction in neonates receiving TPN. Methods: Twenty-eight studies of gallbladder contraction were performed in 18 neonates receiving continuous TPN (median weight, 2.3 kg; range, 1.3 to 7.3; gestational age, 37 weeks; range, 28 to 40; age 6.5 days; range, 2 to 180). Different types of experiments were performed: (1) bolus intravenous infusion of amino acid or fat for 60 minutes at twice the normal infusion rate; (2) bolus intravenous infusion of amino acid or fat for 15 minutes at four times the normal infusion rate. Gallbladder volume was measured by real-time ultrasonography by a single investigator. Measurements were made before starting the bolus infusion and every 15 minutes for 1 hour. Results: The volume of the gallbladder before bolus intravenous infusion was not significantly different between experiments (median, 985; range, 603 to 1,802 mm 3). These volumes are consistent with an enlarged and atonic gallbladder as previously reported in infants receiving parenteral nutrition. In all experiments there was no significant decrease in gallbladder volume after bolus infusion of either amino acids or fat. Conclusions: Contrary to their effects in adults, bolus infusions of amino acids or fat did not induce gallbladder contraction in neonates on TPN. This may have been because of lack of starvation in the neonates and/or the effect of continuous glucose infusion.

On the Measurement of Cholecystokinin

A hormone is a chemical transmitter that is secreted from one part of the body and circulates in the bloodstream to reach a distant target in another part of the body where it exerts its biologic effect. At its inception, this was a revolutionary concept that gave birth to an entire physiological and, later, medical discipline. Early on, hormones were discovered by their biologic actions. However, the physiology of hormones could not be assessed without quantification. Fundamental to the study of hormones was the ability to measure concentrations in the blood. Although biological assays have been the cornerstone of endocrinologic measurements, the development of the radioimmunoassay (RIA) completely changed the field of endocrinology (1). The attractive features of RIA include (a) applicability to most hormones, (b) ease of performance, and (c) relatively low cost, as well as high degrees of (d) accuracy, (e) sensitivity, and (f) specificity. Cholecystokinin (CCK) was discovered in 1928 on the basis of the ability of intestinal extracts to stimulate gallbladder contraction in dogs (2). Later it was recognized that CCK was a potent stimulant of pancreatic enzyme secretion (3). However, it was not until 1966, when CCK was purified, that the primary sequence was determined (4)(5). Early estimates of CCK-like activity in blood were based on biological assays such as pancreatic secretion or gallbladder contraction. However, these estimates were fraught with confounding problems that existed in whole animals, such as the effects of other hormones or neural influences. To circumvent these problems, a sensitive and specific in vitro bioassay was developed (6), but …

Luminal Cholecystokinin and Gastrin Cause Gallbladder Contraction

Cholecystokinin-8 placed in the gallbladder lumen causes gallbladder contraction by a neurally mediated, tetrodotoxin-sensitive mechanism. We wished to determine whether other cholecystokinin-like peptides in the gallbladder lumen cause contraction and whether this response is inhibited by cholecystokinin-receptor antagonists. In this study, we measured gallbladder contraction induced by cholecystokinin-like peptides or by hepatic bile placed in the gallbladder lumen. Isolated gallbladders were suspended in an organ bath while luminal hormones were infused. Gallbladder contraction was measured by continuous monitoring of luminal pressure. Cholecystokinin-8, cholecystokinin-5, and gastrin-17 caused dose-related gallbladder contraction with similar potency when placed in the lumen. Each stimulated 70–80% maximal contraction at a luminal concentration of 10−6M.Cholecystokinin-receptor antagonists CR1409 and loxi- glumide partially inhibited contraction caused by luminal cholecystokinin-8. Bile from fed animals, but not from fasted animals, stimulated gallbladder contraction to 36 ± 4% of maximal when placed in the gallbladder lumen. We conclude that cholecystokinin and gastrin peptides in the gallbladder lumen cause contraction. This may be mediated through receptors of the cholecystokinin-B type, possibly on intrinsic nerves. Bile from fed animals also contains substances that stimulate gallbladder contraction when bile is placed in the gallbladder lumen. These findings suggest intrinsic nerves participate in the postprandial gallbladder response to cholecystokinin.