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J Svanvik

Publications and source records attributed to J Svanvik.

At least 19 recordsLinked to original sources

Location of enkephalinase and functional effects of [Leu5]enkephalin and inhibition of enkephalinase in the feline main pancreatic and bile duct sphincters.

1. Morphological studies have demonstrated enkephalinergic nerve fibres in proximity to the sphincter of Oddi, and opiates are known to contract this sphincter. In this study, the flow resistances in the common bile duct and main pancreatic duct sphincters were studied simultaneously in anaesthetized cats using a perfusion technique. 2. Naloxone did not affect the activity of these sphincters under basal conditions, indicating that there is no basal enkephalinergic tone. 3. The response to [Leu5]enkephalin (0.015-15 micrograms/kg), morphine (1 mg/kg) and ketamine (10 mg/kg) was a naloxone-sensitive increased activity in the sphincters with a raised frequency of phasic contractions. The threshold dose for an effect of [Leu5]enkephalin on the sphincter of Oddi was 0.015 microgram/kg and a maximal response was observed at 0.75 microgram/kg. There were no differences in the response of the main pancreatic duct sphincter and the bile duct sphincter to the different drugs. 4. Immunoautoradiographic studies demonstrated enkephalinase in the sphincter++ of Oddi. 5. Acetorphan (3 mg/kg intravenously), which inhibits endogenous enkephalinase both in the peripheral and the central nervous system when administered parenterally, caused a naloxone-sensitive contraction, whereas thiorphan (3-20 mg/kg), an enkephalinase inhibitor that does not easily penetrate the blood-brain barrier, had no effect on the sphincter of Oddi. 6. These results show that endogenous and exogenous opiates influence the function of the feline sphincter of Oddi and that enkephalins may be involved in the physiological control of this sphincter, although not under basal conditions.

Animals

Effect of short-term indomethacin treatment on the clinical course of acute obstructive cholecystitis.

In acute obstructive cholecystitis the increased intraluminal pressure in the gallbladder is reduced by nonsteroid anti-inflammatory drugs which effectively relieve biliary pain. To investigate if such drugs influence the clinical course, a double-blind study was performed in which indomethacin (suppositories 75 mg b.d.) was tested against placebo in 34 patients with acute obstructive cholecystitis. During the 3-day treatment period both the indomethacin and the placebo group improved significantly as regards pyrexia, pain, abdominal tenderness and leukocytosis. The indomethacin group showed significantly greater improvement than the placebo group in temperature, pain and white blood cell count on day 1, and significantly greater reduction of abdominal tenderness on day 2. The serum bilirubin fell significantly during the 3-day period in the indomethacin, but not the placebo group. The hospital stay in cases without early surgery was significantly shorter in the indomethacin group (5.4 vs. 8.5 days). Because of its favourable effect on the clinical course of acute cholecystitis, rectally administered indomethacin is useful for patients awaiting operation or scheduled for later elective surgery.

Acute Disease

Functional and morphological relationships between the feline main pancreatic and bile duct sphincters.

To analyze the relationships between the bile duct and main pancreatic duct sphincters, the resistance to flow through these sphincters was studied simultaneously with perfusion techniques in anesthetized cats. Basal flow resistance was higher in the pancreatic sphincter than in the bile duct sphincter. The pressure in one duct system was not affected by the flow in the other. The muscular activities in the sphincters were usually well coordinated. Distention of the upper biliary tract or the pancreatic duct system reduced the flow resistance in both sphincters. Cholecystokinin-8 (0.01 micrograms), duodenal distention, and sublingual glyceryl trinitrate (0.4 mg) also relaxed both sphincters, whereas secretin in a dose that induced pancreatic secretion had no consistent effect. Morphine increased flow resistance in both systems. These functional studies indicate that the 2 sphincters share smooth muscle fibers at the level where the flow resistances arise, and there are thus no grounds for separate control of the sphincters. There was no evidence of a functionally common sphincter ampulla. The conclusions drawn from the manometric results were supported by morphological findings in this study.

Animals

Biliary excretion of different sized polyethylene glycols in the cat.

Polyethylene glycol (PEG) 900 is excreted more extensively into bile than mannitol and erythritol. In this study, the biliary recovery of intravenously injected marker molecules was analysed in anaesthetised cats with ligated renal pedicles. It was demonstrated that among polyethylene glycols sized 292-1250 Da, the species sized 1074 Da was maximally excreted in the bile. After 5 h, about 12% of the injected amount of this molecular species was recovered in bile. Both larger and smaller polyethylene glycol molecules had a lower biliary excretion. The distribution of different sized PEGs in the range 766-1250 Da in serum was fairly constant and cannot explain the recovery profile in bile. 14C-Labelled mannitol was recovered in bile to the extent of 0.7% of the amount given i.v. after 5 h, a figure that corresponds to that obtained for polyethylene glycol with a size of 370 Da. Bile/plasma ratios during steady state conditions of labelled PEG 450, PEG 900, PEG 2500 and PEG 4000 were 10, 36, 3 and 4, respectively. The results may be tentatively explained by restricted passage of the larger PEG molecules into the canaliculi, and leakage of the smaller molecules from bile back to plasma.

Animals

Adrenergic influence on bile secretion--an experimental study in the cat.

The influence on bile secretion of electrical stimulation of the splanchnic nerves and arterial infusion of adrenergic agonists was studied in anaesthetized cats. The bile salt secretion was supported by a continuous intravenous infusion of sodium glycocholate. Electrical stimulation of the splanchnic nerves reduced the volume outflow of bile from 0.71 to 0.44 ml h-1 kg-1 body wt and raised the bile acid concentration in bile, while the bile salt secretion rate was not affected. This response was reduced but not blocked by pretreatment with phentolamine, an alpha-adrenergic blocker, at a dose that prevented the blood pressure response. Infusion of noradrenaline, a mainly alpha-adrenergic agonist, into the hepatic artery mimicked the response. Infusion of isoprenaline, a beta-adrenergic agonist, also reduced the volume outflow of bile from the liver. The biliary clearances of mannitol and polyethylene glycol 900, both of which are suggested to reflect canalicular events, were reduced by stimulation of the splanchnic nerves and infusion of noradrenaline. It is concluded that stimulation of the alpha-adrenergic receptors reduces the bile acid-independent bile secretion. This reduction in bile flow induced by stimulation of the splanchnic nerves and infusion of noradrenaline is elicited mainly at the canalicular level.

Adrenergic alpha-Agonists

Hepatobiliary compensation for the loss of gallbladder function after cholecystectomy. An experimental study in the cat.

The side effects of the removal of a functioning gallbladder are surprisingly few, and it has been suggested, but never demonstrated, that the hepatobiliary tract then adjusts to compensate for the loss of gallbladder function. In this study the effects of cholecystectomy on bile acid kinetics, bile flow, and biliary clearance of mannitol were studied in cats 6-8 weeks after cholecystectomy. An enhanced recycling rate of a diminished bile acid pool was found. The bile flow was reduced and the bile acid concentration in hepatic bile was increased, but fasting bile acid secretion rate was not changed. Both when the bile acid secretion rate was reduced by drainage via an acute bile fistula and when it was enhanced by intravenous infusion of glycocholic acid, there was a lower bile acid-independent flow in the cholecystectomy group. This reduced bile flow after cholecystectomy was not explained by the higher proportion of deoxycholic acid present in the bile of the cholecystectomized animals. Biliary clearance of mannitol, which is supposed to reflect the canalicular inflow, was not reduced, indicating that the reduction in bile flow is explained by a reduced fluid secretion or an enhanced fluid reabsorption in the bile ductules and ducts after cholecystectomy. In this manner the bile ducts compensate for the loss of the absorptive function of the gallbladder after cholecystectomy.

Animals

A porcine model for acute distal aortic occlusion.

Periarterial and intramural nerves and lymphatics as well as the vascular endothelium may influence pathophysiologic responses to acute arterial occlusion. For study of such pathophysiologic patterns, experimental models resembling the clinical situation are therefore preferable. In this porcine study acute distal aortic occlusion was mimicked by use of a balloon catheter introduced via a vascular graft anastomosed to the lateral aortic wall. Peripheral circulatory disturbance was assessed by measurements of femoral vein blood flow, skin blood flow in the hind foot and oxygen tension in the calf muscle, which verified the degree of ischemia. During the 4-hour ischemic period, repeated arterial and venous blood gas analyses showed increasing acidosis in effluent venous blood from the hind limbs, which after reperfusion slowly normalized. As highly reproducible conditions are achievable with the present experimental model, it can be used for studies of pathophysiologic responses to acute distal aortic occlusion.

Animals

Inhibition of prostaglandin synthesis as a treatment for biliary pain.

Twenty patients with confirmed gallbladder disease were treated with intravenous indomethacin during 24 separate attacks of biliary pain. In all cases the pain was promptly relieved and there were no important side-effects. Indomethacin, and inhibitor of prostaglandin synthesis, may reduce intraluminal pressure in the gallbladder, and relieve pain.

Cholelithiasis

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.

Animals