The Effect of Choleretic and of Hydrocholeretic Agents on Bile Flow and Bile Solids in the Isolated Perfused Liver

Bräuer, Ralph W.; Pessotti, Rita L.

doi:10.1126/science.115.2980.142

Cited by 17 publications

(5 citation statements)

References 4 publications

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“…Extracorporeal liver perfusion has been utilised in an experimental setting for many years (1) to study unique components of liver physiology and more recently as a possible mechanism of liver support (2). One new field of interest involves employing machine perfusion as a possible mechanism for preservation and resuscitation of injured livers before transplantation.…”

Section: Introductionmentioning

confidence: 99%

“…One important aspect of liver physiology is that of bile production, which is necessary in order for biliary canaliculi to remain in a functional state and excretion of hydrophobic compounds to be maintained (3). This in return relies on a choleretic stimulus from a constant supply of bile acids (1), the majority of which are delivered in vivo via the enterohepatic circulation. The isolated circuit clearly precludes the latter because bile is excreted and discarded.…”

Section: Introductionmentioning

confidence: 99%

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Optimisation of Bile Production during Normothermic Preservation of Porcine Livers

Imber

Peter

Cenarruzabeitia

et al. 2002

American Journal of Transplantation

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Machine perfusion of livers may provide a mechanism for extended preservation of marginal donor organs before transplantation, as well as a method for viability assessment. It has proved possible in a series of experimental porcine liver perfusions to maintain liver viability for up to 72 h. However, a reduction in bile production with associated histological evidence of cholestasis was seen after 10 h of perfusion, damaging the biliary canaliculi during the preservation period and leaving these organs in an unacceptable condition for transplantation. It was proposed that reduction in bile production was the result of a relentless depletion of available bile salts, gut recirculation not being possible and de-novo synthesis being unable to keep up with loss. This was proved by measuring porcine native bile acids within serial perfusate and bile samples using gas chromatography mass spectrophotometry. It was shown that all three native pig bile acids were decreased to 30% of their original value by 20 h of unsupplemented perfusion. An infusion of taurocholate managed to maintain bile production at physiological levels throughout the 20-h period (8 mL/h ∫ 0.75). It was successfully incorporated by the porcine livers into bile. We propose to use this circuit as a novel means of preserving donor livers for transplantation in which the organ is maintained at normal body temperature and perfused with blood. This will reduce ischaemia reperfusion injury and may enable prolonged preservation. The modification described ensures optimal bile production over the entire perfusion period, preventing inspissation and subsequent damage to the canaliculus.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Optimisation of Bile Production during Normothermic Preservation of Porcine Livers

Imber

Peter

Cenarruzabeitia

et al. 2002

American Journal of Transplantation

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“…Since bile flow rate has been shown to be predominantly dependent upon bile salt secretion (6)(7)(8)(9), this suggests that primary bile acid secretion may be impaired 'by estrogen. The observation that the bile flow rate in ethinylestradiol-treated animals was markedly less than that of control rats, both during the initial 24 hr of bile drainage and during the 9-hr study period was of great interest.…”

mentioning

confidence: 99%

Effects of Ethinylestradiol-Induced Cholestasis on Bile Flow and Biliary Excretion of Estradiol and Estradiol Glucuronide by the Rat

Kreek

Peterson

Sleisenger

et al. 1969

Experimental Biology and Medicine

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The phenolic steroid hormones estrone and estradiol, are excreted in bile and undergo an enterohepatic circulation in the rat and in man. I t has been shown that high doses of exogenous estrogen may impair hepatic excretory function in human females and in the rat (1, 2 ) . There is also evidence that endogenous hormones may cause abnormalities of liver function or cholestasis during late pregnancy (3)(4)(5), and that in those individuals who have suffered from cholestatic jaundice of pregnancy or pruritus gravidarum, moderate or low dose of estrogen administered in the nonpregnant state will reproduce the symptoms and liver function test abnormalities that occurred during pregnancy (4, 5 ) . The present study was carried out to determine whether administered estrogen impairs bile flow and biliary excretion of labeled estrogen in the rat.Methods and Materials. Female Sprague-Dawley rats, weighing from 150 to 180 g were fed ethinylestradiol (0.5 mg in saline suspension, by oral tube) daily, for 9 days. Litter-mate control animals were similarly saline sham-fed. On the tenth experimental day common bile duct cannulation and femoral vein catheterization were performed with the rats under light ether anesthesia. Each animal was then confined to a modified plastic restraining cage. Constant intravenous hydration with 5% dextrose and saline solution administered by a Harvard infusion apparatus at a rate of 0.0764 ml/min, and constant room temperature conditions, 25-26', were maintained throughout the entire study. Public Health Service F2 A.M. -30,036.On the eleventh experimental day, 18-20 hr after surgery and 40-48 hr after the last dose of ethinylestradiol, a tracer dose of radioactive estrogen (estradiol or estradiol glucuronide) and bromsulfophthalein ( 10 mg) were administered intravenously via the femoral catheter, in 0.4 ml of 50% ethanolsaline solution, followed by a 1.0-ml saline flush. Bile was collected in 10-min fractions during the first hour, 15-min fractions during the second hour, 30-min fractions during the next 2 hr, and at 1-or 2-hr intervals up to a total of 9 hr. At the end of the collection periods, the animals were killed, the livers were examined grossly and under light microscopy with hematoxylin and eosin sections.Radioisotopes, estradiol-l7p-6, 7-3H, 5.6 Ci/mmole, istradiol-1 7P-4J4C, 8.18 mCi/ mmole and estradiol-6, 7-3H, 1 7/3-~-glucuronide, 1.0 Ci/mmole, were obtained from the New England Nuclear Corporation and were repurified by paper chromatography prior to use. The activity of the radioactive estrogen solutions to be administered was measured a t the time of each injection. Bile samples were measured for volume. Qualitative analysis for the appearance of bromsulfophthalein in the bile was made in all control and estrogentreated animals. Aliquots were taken for measurement of radioactivity. To each bile aliquot, 50 pl or less, was added 2 ml of ethanol and 10 ml of toluene-POPOP phosphor solution. Quench correction was carried out by the addition of an appropriate internal standard to ...

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“…Reduction in bile flow may be related to INTRODUCTION It is generally accepted that the bile acid salts are major determinants of bile flow. This view is based, in part, on the knowledge that glycine and (or) taurine conjugates of chenodeoxycholic,' deoxycholic, and cholic acids are present in much higher concentrations in the bile than in the plasma of many mammalian species (1), and that infusions of some of these compounds cause an increase in bile flow and bile acid excretion (2,3).…”

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confidence: 99%

Effect of sodium taurolithocholate on bile flow and bile acid excretion

Javitt¹,

Emerman²

1968

J. Clin. Invest.

244

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The Effect of Choleretic and of Hydrocholeretic Agents on Bile Flow and Bile Solids in the Isolated Perfused Liver

Cited by 17 publications

References 4 publications

Optimisation of Bile Production during Normothermic Preservation of Porcine Livers

Optimisation of Bile Production during Normothermic Preservation of Porcine Livers

Effects of Ethinylestradiol-Induced Cholestasis on Bile Flow and Biliary Excretion of Estradiol and Estradiol Glucuronide by the Rat

Effect of sodium taurolithocholate on bile flow and bile acid excretion

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