Pharmacological and physiological doses of insulin and determinants of bile flow in dogs

1983 ◽  
Vol 245 (1) ◽  
pp. G157-G163
Author(s):  
C. A. Garberoglio ◽  
H. M. Richter ◽  
A. Henarejos ◽  
A. R. Moossa ◽  
A. L. Baker

The role of insulin in control of bile secretion is uncertain. To study the mechanism of choleresis produced by large doses of insulin, bile was collected through modified Thomas cannulas from dogs anesthetized with pentobarbital. Animals received pipenzolate methylbromide, sodium taurocholate, and [14C]erythritol. After bile flow had stabilized three animals received infusions of insulin at 2, 4, 13, 26, 35, and 70 mU . kg-1 . min-1 for 40 min each. Bile and [14C]erythritol clearance increased (P less than 0.005), but bile salt output remained constant, suggesting that the choleresis was mainly due to enhanced bile salt-independent canalicular flow. Plasma insulin and glucagon levels also rose when insulin was infused. To exclude the possible effects of glucagon three additional animals received somatostatin (800 ng . kg-1 . min-1) along with infusions of insulin. Bile flow and [14C]erythritol clearance again increased significantly, but glucagon levels remained low, suggesting that the effects on bile flow were due to insulin alone. To determine whether physiological doses of insulin altered bile flow dogs were anesthetized with pentobarbital and received pipenzolate methylbromide, taurocholate, [14C]erythritol, and somatostatin (800 ng . kg-1 . min-1). Insulin (0.2 and 0.8 mU . kg-1 . min-1) was infused through the portal vein for 1 h each. Bile flow and [14C]erythritol clearance increased with insulin (0.8 mU . kg-1 . min-1; P less than 0.02), suggesting that the choleresis may have been due to bile salt-independent canalicular flow. Plasma insulin rose to physiological postprandial levels. These studies demonstrate that pharmacological and physiological levels of insulin administered to dogs produce a significant choleresis. Thus insulin may play an important role in the regulation of bile secretion.

1982 ◽  
Vol 242 (4) ◽  
pp. G313-G318 ◽  
Author(s):  
J. S. Reed ◽  
N. D. Smith ◽  
J. L. Boyer

A technique is described for perfusion of livers from the little skate, Raja erinacea, in the isolated state at 15 degrees C utilizing a recirculating, well-oxygenated elasmobranch Ringer solution. Bile flow and oxygen consumption were optimal and remained relatively constant over a 4- to 5-h perfusion at portal vein pressures of 2.5-5.0 cm Ringer. At these pressures, bile flow rates were comparable to values previously observed in the free-swimming skate. In contrast to mammalian species, bile secretion in the elasmobranch is particularly sensitive to small changes in perfusion pressure. Hepatic clearance of sulfobromophthalein and [14C]sodium taurocholate demonstrated initial fractional disappearance rates that were also similar to values obtained in vivo. Only small amounts of sulfobromophthalein appeared in bile by 5 h, whereas 78.5 +/- 6.5% of [14C]sodium taurocholate was recovered in bile at this time. These experiments establish portal vein perfusion pressures for study of skate livers in the isolated state in which oxygen consumption is maximal and organic anion clearance from perfusate to bile exceeds values obtained in vivo.


1978 ◽  
Vol 55 (3) ◽  
pp. 253-259 ◽  
Author(s):  
R. J. Vonk ◽  
A. B. D. van Doorn ◽  
J. H. Strubbe

1. In freely moving, unanaesthetized rats bile flow was measured continuously over the whole day-night cycle. Bile composition was analysed and the influence of food intake on bile flow was investigated. 2. In both sexes a distinct circadian variation of bile production was observed. The mean night-time production was 50% higher than the day-time value for female rats and 38% for male rats. In the morning when the light was switched on, a sharp decrease in secretion rate was prominent and bile flow gradually increased in the afternoon. 3. The pattern of food intake was positively correlated with the pattern of bile secretion. During fasting only the general level of bile flow decreased, but the circadian variation persisted. Refeeding again increased the mean level of bile flow. 4. The chenodeoxycholate/cholate ratio in these rats with permanent bile fistulae was higher than in rats with ‘acute’ bile fistulae and changed during the day-night cycle. The ratio decreased from 1.01 at 05.00 hours to a minimum of 0.41 at 15.00 hours. 5. During the day-night cycle the sodium, potassium, calcium and cholesterol concentrations were relatively constant. The total bile salt concentration was only slightly changed, so that both the bile salt-dependent fraction and the bile salt-independent fraction were subject to about the same circadian variations.


1990 ◽  
Vol 68 (1) ◽  
pp. 136-138 ◽  
Author(s):  
Francis R. Sutherland ◽  
Roy M. Preshaw ◽  
Eldon A. Shaffer

Cyclosporine A is reported to cause cholestasis, but the evidence is confounded by anesthesia and surgery used in acute experiments. To better investigate the effect of cyclosporine on the liver, bile output was directly measured in three cholecystectomized dogs by cannulating the common duct through a chronic duodenal fistula. Control studies were done 1 month after surgery. Cyclosporine in oral doses of 5, 15, and 50 mg∙kg−1∙d−1 was then given for consecutive 1-week periods. Twice during each study period, bile output was measured for 5 h in fasted, awake animals: 3 h to establish basal conditions, followed by 2 h of taurocholate infusions at 1 and then 2 μmol∙kg−1∙min−1. Under basal conditions, bile flow rose with each dose of cyclosporine, increasing 63, 127, and 179% above control with cyclosporine 5, 15, and 50 mg∙kg−1∙d−1 respectively. Bile flow increased similarly during taurocholic acid stimulation. Cyclosporine had no effect on bile salt or bilirubin secretion. In this chronic dog model isolated from other causes of cholestasis, cyclosporine did not induce cholestasis but rather caused a dose-related choleresis without any change in bile salt secretion.Key words: cyclosporine A, bile, cholestasis, hepatotoxicity.


1996 ◽  
Vol 270 (5) ◽  
pp. G804-G812 ◽  
Author(s):  
T. Yamada ◽  
M. Hoshino ◽  
T. Hayakawa ◽  
Y. Kamiya ◽  
H. Ohhara ◽  
...  

The objective of this study was to characterize the bile secretion, including the composition of biliary bile acids, bile salt pool size, and transcytotic vesicle transport, in a rat model of subacute intestinal inflammation induced by indomethacin. Indomethacin treatment significantly decreased bile acid-independent bile flow and biliary secretion of bile acid and cholesterol, while increasing biliary phospholipid output in vivo. Although indomethacin treatment did not change the bile salt pool size in vivo, alpha- and beta-muricholic acids were significantly deceased and hyodeoxycholic and deoxycholic acids were increased in bile. Bile flow and the transport maximum of taurocholate did not decrease, and biliary horseradish peroxidase output was significantly enhanced in isolated perfused livers from indomethacin-treated rats. Endotoxin in the portal blood was significantly increased in rats treated with indomethacin. Clindamycin slightly reduced intestinal inflammation but significantly prevented decreases in bile flow, bile acid output, and transport maximum of taurocholate. We conclude that, although biliary secretory function was apparently decreased in vivo, that of hepatocyte function was maintained in this model.


1986 ◽  
Vol 64 (10) ◽  
pp. 1316-1320 ◽  
Author(s):  
S. M. Strasberg ◽  
R. G. Ilson ◽  
C. E. Bear

Bile salt dependent flow and electrolyte secretion in response to two bile salts were studied in awake rabbits. It was found that sodium glycodeoxycholate had a much greater choleretic and cholioneretic efficiency than sodium taurocholate. The effect of the bile salts on flow and electrolyte secretion was not linear across the range of bile salt secretion rates studied. When amiloride was administered significant decreases in choleretic and cholioneretic efficiencies occurred, but furosemide had no effect. It is concluded that bile salts stimulate electrolyte transport via amiloride inhibitable cellular processes, and that this electrolyte transport is in part responsible for bile salt dependent bile flow.


1989 ◽  
Vol 96 (4) ◽  
pp. 1142-1150 ◽  
Author(s):  
Paola Loria ◽  
Nicola Carulli ◽  
Giuseppe Medici ◽  
Alberto Tripodi ◽  
Rossella Iori ◽  
...  

1991 ◽  
Vol 261 (5) ◽  
pp. G775-G780 ◽  
Author(s):  
K. Beckh ◽  
R. Arnold

Although the biliary system is innervated by the autonomic nervous system, little is known about the regulation of bile secretion by hepatic nerves. In rat liver perfused in situ with constant pressure and erythrocyte-free medium, hepatic nerves were electrically stimulated (20 V, 20 Hz, 2 ms) by a platinum electrode placed around the hepatic artery and portal vein. Nerve stimulation caused a decrease in bile flow, bile acid secretion, and portal flow. The nerve effects on bile secretion were mediated via alpha 1-receptors. In this system, artificial reduction of perfusion flow by 30% led to a similar decrease of bile flow. In perfusion systems with constant flow and erythrocyte-free medium or with constant pressure and erythrocyte-containing medium, the nerve effects were reproduced despite the altered hemodynamics and the increased oxygen supply. In addition, partial inhibition by sodium nitroprusside of the nerve-induced reduction of portal flow had little effect on the reduction in bile secretion. In conclusion, a direct effect on bile formation was suggested. Yet an additional role of a vascular-mediated effect could not definitively be excluded. With the use of inhibitors of prostanoid synthesis the nerve effects on bile secretion were markedly reduced, suggesting a mediating or modulating role of prostanoids.


2020 ◽  
Vol 04 (03) ◽  
pp. 291-302
Author(s):  
Mariam F. Eskander ◽  
Christopher T. Aquina ◽  
Aslam Ejaz ◽  
Timothy M. Pawlik

AbstractAdvances in the field of surgical oncology have turned metastatic colorectal cancer of the liver from a lethal disease to a chronic disease and have ushered in a new era of multimodal therapy for this challenging illness. A better understanding of tumor behavior and more effective systemic therapy have led to the increased use of neoadjuvant therapy. Surgical resection remains the gold standard for treatment but without the size, distribution, and margin restrictions of the past. Lesions are considered resectable if they can safely be removed with tumor-free margins and a sufficient liver remnant. Minimally invasive liver resections are a safe alternative to open surgery and may offer some advantages. Techniques such as portal vein embolization, association of liver partition with portal vein ligation for staged hepatectomy, and radioembolization can be used to grow the liver remnant and allow for resection. If resection is not possible, nonresectional ablation therapy, including radiofrequency and microwave ablation, can be performed alone or in conjunction with resection. This article presents the most up-to-date literature on resection and ablation, with a discussion of current controversies and future directions.


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