Lars Thulin

Effects of somatostatin on hepatic bile formation

Somatostatin is a peptide that has anticholeretic properties in the dog. The purpose of the present work was to investigate if somatostatin is an anticholeretic agent in humans also. The effects of intravenous infusion of somatostatin on hepatic bile flow and biliary electrolytes and secretion of biliary lipids were studied in 7 patients with complete biliary drainage who had been operated on for choledocholithiasis. Somatostatin, 250 microgram/h, was found to decrease the hepatic bile secretion by approximately 30%. The peptide also reduced the outputs of bile acids, cholesterol, and phospholipids and the outputs of sodium, potassium, and chloride. The concentrations of the biliary lipids were not significantly changed. Somatostatin inhibited the erythritol clearance in the 2 patients studied by approximately 25%. The present study thus provides evidence that somatostatin inhibits bile formation in humans. It appears as if the reduction in bile production is mainly due to decreased canalicular bile flow. It is possible that this effect of somatostatin is attributable to inhibition of bile acid synthesis or of transport-secretion of bile acids, or both.

Circulatory effects of VIP in anesthetized man

VIP was given intravenously over 1 min at the doses 0.1 and 0.2 micrograms X kg X min-1 to twenty-one anesthetized patients undergoing abdominal surgery. Intra-arterial blood pressure was monitored and various blood flows were measured simultaneously by electromagnetic technique. Following VIP, intra-arterial blood pressure was decreased. The blood flows were increased in the gastroduodenal-, and the left gastric arteries. The flow in the hepatic artery proper was increased only following the 0.2 micrograms dose. The flow in the superior mesenteric artery varied considerably inter-individually. In branches supplying only the small intestine, it seemed to be unaffected. The flow in the splenic artery was decreased in normal-sized spleens, but unaffected in enlarged spleens. The flow in the external iliac artery initially decreased and thereafter increased. Changes in vascular resistances showed that VIP acted as a vasodilator in the splanchnic region except in the superior mesenteric vasculature, where it was ineffective. In normal spleens it was a vasoconstrictor. In the external iliac artery, an initial insignificant vasoconstriction was followed by vasodilation. It seemed that VIP acts directly on the vessels and has a specific pattern of vasoactivity of probable physiological significance.

Endoscopic Fluorescein Flowmetry in the Evaluation of Gastric and Duodenal Mucosal Blood Flow

Fluorescein flowmetry (FF) implies the measurement of a relative capillary blood flow, expressed as an index--that is, the ratio between the maximum fluorescence, obtained during the first circulatory passage of sodium fluorescein (Na-F), and the rise time, defined as the time interval between 10% and 90% of the maximum fluorescence. The aim of this study was to develop FF to be used during endoscopy for the evaluation of ventricular and duodenal mucosal blood flow. FF was applied during gastroduodenoscopy in 38 patients with normal mucosa, as verified by histopathologic examination. The blood flow index did not differ significantly for the mucosa of the fundus, corpus, and antrum. However, when compared with the duodenal mucosa, the blood flow index of the ventricular mucosa was almost twice as high (P less than 0.01). This, in turn, was due to a significantly higher maximum fluorescence in the ventricular mucosa (P less than 0.01), indicating a denser capillary network than in the duodenal mucosa. Since FF is a reliable method, easy to perform and without complications, it is suitable whenever mucosal blood flow warrants measurement during endoscopy.

Anticholeretic effects of substance P and somatostatin

The aim of the present work was to study the effect of substance P (SP) and somatostatin (SST) on hepatic bile flow. For this purpose a total of 54 anesthetized mongrel dogs were used. The gallbladder was excluded by ligation of the cystic duct and a common duct fistula was created by insertion of a catheter into the common duct. Both SP and SST were found to exert an anticholeretic effect in the dog. SST was also found to be anticholeretic in man. In the dog, SP was infused at dosages from 0.5-20 ng kg-1 min-1 and exerted a significant anticholeretic effect at a dosage of 2.5 ng or higher. At dosages of 2.5 and 20 ng kg-1 min-1, SP decreased the basal bile secretion by about 20 and 40% respectively. The decrease in bile flow was accompanied by decreased outputs of sodium, potassium, chloride, bicarbonate and amylase. With taurocholate-stabilized and taurocholate-stabilized and hormone-induced bile secretion, SP had the above mentioned effects and in addition the output of bile acids decreased. The effect of SP occurred within minutes and after withdrawal of SP there was a positive rebound effect, with a magnitude of about 30% following the 20 ng dosage. SST at dosages from 20-1000 ng kg-1 min-1 induced an anticholeretic effect with a magnitude of 10-25%. With both basal and taurocholate-stabilized bile secretion, the outputs of bile, bile acids and electrolytes decreased during the infusion period and remained diminished for 10-20 min after termination of the infusion. Unlike SP, SST had no anticholeretic effect in the presence of CCK or secretin. A simultaneous infusion of SP and SST decreased bile flow more than either agent alone. The anticholeretic effect of SST was verified in five patients. They had all been operated on for choledocholithiasis. In four patients a complete diversion of bile was obtained with a Foley catheter in the common duct and in the fifth patient from an impacted stone in the common duct. During infusion of SST, 250 ug h-1, the outputs of hepatic bile and bile acids decreased while the outputs of cholesterol and phospholipids were unchanged. The serum bile acid concentration was unaffected by SST and therefore SST is suggested to exert an inhibitory effect on bile acid synthesis. The changes in electrolyte outputs induced by SST in man corresponded to those in the dog.(ABSTRACT TRUNCATED AT 400 WORDS)