J. Svanvik

Effects of Intra-arterial Prostaglandin E2 on Gallbladder Fluid Transport, Motility, and Hepatic Bile Flow in the Cat

The effects of intra-arterial infusion of prostaglandin E2 on gallbladder concentrating function, motility, and hepatic bile flow were studied simultaneously in the anesthetized cat by means of a perfusion technique. Prostaglandin E2 reversibly inhibited gallbladder net fluid absorption and in some cases reversed the direction of transport to a net fluid secretion. A contraction of the gallbladder and an increased flow of hepatic bile were seen during prostaglandin infusion. The results are discussed in relation to the role of prostaglandins in the pathophysiology of cholecystitis.

Gallstones and Previous Cholecystectomy in 77-to 78-Year-Old Women in an Urban Population in Sweden

A randomly selected sample of 120 women, born in 1906-1907 and living in the city of Gothenburg, were invited to an ultrasound examination for gallstone disease. One hundred and nine subjects participated in the study, and among these, 24% gave a history of a previous cholecystectomy, 27% had gallstones, and 49% had no stones in the gallbladder. Among the women with stones in the gallbladder only 35% had associated symptoms. The design of the study enabled a comparison among women with no stones in the gallbladder, with gallstones, and with a previous cholecystectomy. Women with gallstones, previous or present, had a higher body weight, body mass index, skinfold thickness, and serum triglyceride level than subjects without gallstones.

Influence of Electrical Vagal Stimulation and Acetylcholine on the Function of the Feline Gallbladder

The effects of electrical stimulation of the vagus nerves on the function of the feline gallbladder and hepatic bile outflow were studied with a perfusion technique in vivo. After elimination of the muscarinic receptors with atropine, efferent stimulation of the cut vagus nerve in the neck relaxed the gallbladder, reduced the net water absorption rate across its wall, and increased the bile outflow from the liver. The results imply that the concentrating function of the gallbladder and the bile formation in the liver are under regulatory control by noncholinergic, nonadrenergic nerve fibres in the vagus nerves.

The Effects of Morphine and Enkephaline on Gallbladder Function in Experimental Cholecystitis: Inhibition of Inflammatory Gallbladder Secretion

Administration of morphine or its derivatives is the traditional way to treat biliary pain. Despite the common use of morphine and its analogues in patients with cholecystitis and biliary pain, their effects on the function of the inflamed gallbladder are not known. In the present study it is demonstrated that morphine usually contracts the normal gallbladder but does not influence the fluid transport across the mucosa. In experimental cholecystitis morphine and enkephaline do not further contract the gallbladder but, by specific opioid receptors, reduce the inflammatory fluid secretion by the mucosa. In case of obstruction of the gallbladder, fluid secretion by the mucosa will distend its wall and induce biliary pain. It is suggested that the pain-relieving effect of morphine in cholecystitis and attacks of biliary pain is mediated not only by a central analgesic effect but also by an influence on the function of the inflamed gallbladder.

A Comparison of Glucagon, Gastric Inhibitory Peptide, and Secretin on Gallbladder Function, Formation of Bile, and Pancreatic Secretion in the Cat

The effects of glucagon, gastric inhibitory peptide (GIP), and secretin on the concentrating mechanism and the motility in the feline gallbladder have been studied in vivo. A technique by which the gallbladder in situ was perfused by an electrolyte solution made possible a simultaneous study of the motility and of the net transport of water and electrolytes across the gallbladder wall. Secretin (0.6 microgram per kg/h) was found to abolish the net absorption of water, Na+, and HCO3- and strongly reduce the net absorption of K+ and Cl-, whereas neither glucagon (1--20 microgram per kg/h) nor GIP (1--30 microgram per kg/h) was found to significantly influence the concentrating function of the gallbladder. The motility of the gallbladder was not influenced by the peptides. The formation of bile and pancreatic secretion was not changed by glucagon or GIP, whereas secretin had a potent effect.

The Influence of Pregnancy and Contraceptive Steroids on the Biliary Tract and Its Reference to Cholesterol Gallstone Formation

The evidence that pregnancy and the use of contraceptive steroids are associated with increased risk of cholesterol gallstones is reviewed from a physiologic viewpoint. Hepatobiliary functions known to be involved in gallstone formation are physical and chemical composition of bile; nucleation retention and crystal growth; decreased gallbladder motility; enterohepatic circulation of bile acids; speed of gastric emptying and intestinal transit time. In pregnancy many changes in bile acid concentration and pool size have been documented in animals and women with conflicting results. Late pregnant women have enlarged gall bladders that empty slowly in response to food and prolonged intestinal transit time but not gastric emptying has been reported. Cholesterol saturation of bile is increased. Estrogens are known to bind to receptors in hepatocytes and gall bladder. During estrogen administration cholesterol saturation in bile increases the bile acid pool size decreases synthesis of bile acids declines and recycling of bile acids increases with increased fecal losses of bile acids. Progestins have the opposite effects favoring bile acid synthesis. Progesterone has a quieting effect on smooth muscle possibly causing some of the complaints of pregnancy and oral contraception such as heartburn and constipation. These changes with the possibility that emptying of the gall bladder is incomplete give cause for the association between oral contraception and gallstones.

Enzyme Substitution in Chronic Pancreatitis: Effects on Clinical and Functional Parameters and on the Hydrogen (H2) Breath Test

Ten patients with chronic pancreatitis (with abdominal pain and/or diarrhoea) were treated in a double-blind multiple cross-over trial with Pankreon granules 20 g per day or placebo during three periods of one month each. Pain and bowel habits were recorded. Faecal fat and breath hydrogen (H2) excretion were analyzed during the last days of each treatment period. The pain score was initially low in all patients and was not affected by enzymes. The number of daily bowel movements was reduced from 3.16 to 2.32 (n.s.). Faecal fat excretion per 72 hrs was reduced from 357 +/- 158 mmol free fatty acid to 226 +/- 98 mmol (p less than 0.05). With placebo treatment H2 excretion (from 60 and 180 min after a standard breakfast) was significantly increased compared with 19 healthy volunteers (p less than 0.05). It was not significantly reduced by enzymes. In 28 comparisons the H2 output between 60 and 180 min was correlated to faecal fat. In eight patients the oro-coecal transit-time could be determined by the H2 breath test. The transit-time did not differ from that of ten healthy volunteers and remained unchanged by enzymes. Carbohydrate maldigestion occurs parallel to fat maldigestion in chronic pancreatitis, and is not sufficiently reduced by 20 g of pancreatic enzymes.

The influence of somatostatin on gallbladder response to intraduodenal acid and autonomic nerve stimulation in the cat.

The influence of somatostatin on the concentrating function and motility of the feline gallbladder has been studied with perfusion techniques in vivo. Somatostatin did not cause any change in the basal volume or concentrating function of the gallbladder. Duodenal acidification and also efferent electrical stimulation of the vagus nerves after atropinization reduced the net water absorption from the gallbladder, and these effects were blocked by intravenous somatostatin. The enhanced rate of net water absorption in response to electrical stimulation of the splanchnic nerves, however, was not influenced by somatostatin. Both the gastrointestinal peptides vasoactive intestinal peptide (VIP) and secretin reduce the net water absorption in the gallbladder. The blocking effect of the gallbladders response to duodenal acid might be explained by an inhibition by somatostatin of secretin release from the duodenum. The inhibition of the gallbladders reaction to vagal stimulation can be explained by a suppression of VIP release from noncholinergic, nonadrenergic nerve fibres in the gallbladder wall. Apart from the earlier described interference with gallbladder emptying, somatostatin seems to affect the regulation of the gallbladders concentrating function. The results are discussed in view of the recent observation that patients with somatostatinoma characterized by high levels of circulating somatostatin usually have gallstone disease.

Adrenergic Influence on Gallbladder Function in Experimental Cholecystitis

In experimental cholecystitis a net secretion of fluid to the gallbladder lumen is seen in animals with morphological signs of acute inflammation. This fluid secretion, which increases the intraluminal pressure in the obstructed gallbladder, is suggested to be influenced by non-cholinergic intramural gallbladder nerves activated by prostaglandins. In the present study in vivo we show that this fluid secretion, measured by a perfusion technique, is markedly inhibited by electrical activation of the splanchnic nerves that contain adrenergic fibres to the gallbladder and by intravenous administration of an alpha 2-adrenergic agonist, demonstrating that this fluid secretion can be modulated by activation of alpha 2-adrenergic receptors. In patients with an obstructed gallbladder outlet, inhibition of this secretion may reduce gallbladder distension and thus relieve biliary pain. The results suggest that pharmacological activation of adrenergic mechanisms could be useful in the treatment of cholecystitis and biliary pain.

Net Water Absorption and Mucosal Morphometry of Ileal Reservoirs and of Ileal Segments Transposed to the Colon in the Cat

New water absorption and changes in villous height were studied in ileal reservoirs and in ileal segments transposed to the colon in the cat. A continuous perfusion technique was used to estimate net water absorption. The villous height was reduced both in ileal reservoirs and in the transposed segments compared with normal ileum. The serosal area of the reservoir was significantly increased compared with the initial segment used in construction of the reservoir. The reservoir showed a reduced net water absorption rate per unit serosal area compared with a control segment, but when the absorption of the whole reservoir was compared with that of a control segment of the same initial length, there was no significant change. In the transposed segments no significant change in net water absorption could be revealed. Data from both series of experiments showed a positive correlation between net water absorption per unit serosal area and villous height. Blood flow registration in ileal segments transposed to the colon showed a blood flow of the same magnitude in the transposed segment as in the control segment.