Long-Term Perfusion of Isolated Rat Liver

Bartošek, I.; Guaitani, A.; Garattini, Silvio

doi:10.1159/000136341

Cited by 25 publications

(6 citation statements)

References 17 publications

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“…Nevertheless, a steady-state perfusate concentration is quickly achieved, and since this concentration is higher than the normal portal venous bile salt concentration, the net bile salt extracted per passage is similar to that in vivo. The decrease in function that occurred between 2 and 3 h was variable and is consistent with other data2 (27) suggesting that 3 h of perfusion represents the upper limit of usefulness of this preparation.…”

Section: Resultssupporting

confidence: 90%

The regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the isolated perfused rat liver.

Cooper¹

1976

J. Clin. Invest.

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A B S T R A C T The effect of perfusion of an isolated rat liver on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase was studied. In liver removed during the basal period of the diurnal cycle of enzyme activity, a 227±41% increase in enzyme activity occurred after 3 h of a l)lasna-free perfusion. This could be prevented by the addition of cycloheximide or pure cholesterol (dispersed with lecithin) to the perfusate. In contrast, the continuous addition of taurocholate or taurochenodeoxycholate, alone or in combination, at a variety of rates did not prevent the increase in enzyme activity. The added bile salts were efficiently extracted from the perfusate and excreted in the bile. The addition of these bile salts to a cholesterol-enriched perfusate did not alter the effect obtained with cholesterol alone.If the perfusate contained whole serum, the increase induced by perfusion in the basal period was smaller (88±27%) than with plasma-free perfusate. Again, the major bile salts of the rat failed to prevent the increase in enzyme activity induced by liver perfusion.If livers were removed and perfused at the height of the diurnal cycle of enzyme activity, the enzyme activity remained high (2+10% increase) rather than decreasing, as occurs in vivo. If cholesterol was added to these perfusions, a 52-+-4% decrease was induced. Bile salt addition induced no decrease. From these results it is concluded that the major bile salts are not direct regulators of hepatic cholesterol synthesis, but pure cholesterol, in the absence of bile salt or lipoprotein, is able to initiate the mechanism that represses hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase.

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Section: Resultssupporting

confidence: 90%

The regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the isolated perfused rat liver.

Cooper¹

1976

J. Clin. Invest.

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“…Differentiated decrease of microsomal enzyme activities has been previously observed in our laboratory (4); the hydroxylation of aniline and O-demethyla tion o f p-nitroanisol did not change substantially during 4-hour perfusion while the N-demethylation of aminopyrine was reduced by about 40 %. A pretreat-ment of the liver donors with phénobarbital to obtain an induction of micro somal enzymes did not influence the effect exerted by the perfusion.…”

supporting

confidence: 67%

“…Moreover, in non-sterile conditions the bacterial contamination of the isolated organ begins to alter its metabolic activity after 3 h of perfusion (3).…”

Section: Resultsmentioning

confidence: 99%

“…The technique of perfusing isolated liver is frequently used in studies of drug metabolism (5). It is therefore of general interest to obtain more informa tion about the changes of microsomal enzyme activities during the perfusion.…”

mentioning

confidence: 99%

“…These changes of the metabolic activity are different with various substrates (3,4). Moreover, the conditions of liver perfusion as seen in the preliminary fasting of the organ donor (7), the composition of the perfusion medium (8) and the presence of extrahepatic tumors (2,6,21) may influence the results and alter their significance to a large extent.…”

mentioning

confidence: 99%

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Differential Effects of Fasting and Nicotinic Acid on Various Enzymatic Activities of the 9,000 <i>g</i> Fraction of the Perfused Rat Liver

1975

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The multiple-indicator dilution technique for characterization of normal and retrograde flow in once-through rat liver perfusions†

et al. 1989

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The technique of normal and retrograde rat liver perfusion has been widely used to probe zonal differences in drug-metabolizing activities. The validity of this approach mandates the same tissue spaces being accessed by substrates during both normal and retrograde perfusions. Using the multiple-indicator dilution technique, we presently examine the extent to which retrograde perfusion alters the spaces accessible to noneliminated references. A bolus dose of 51Cr-labeled red blood cells, 125I-albumin, 14C-sucrose and 3H2O was injected into the portal (normal) or hepatic (retrograde) vein of rat livers perfused at 10 ml per min per liver. The outflow perfusate was serially collected over 220 sec to characterize the transit times and the distribution spaces of the labels. During retrograde perfusion, red blood cells, albumin and sucrose profiles peaked later and lower than during normal perfusion, whereas the water curves were similar. The transit times of red blood cells, albumin and sucrose were longer (p less than 0.005), whereas those for water did not change. Consequently, retrograde flow resulted in significantly larger sinusoidal blood volumes (45%), albumin Disse space (42%) and sucrose Disse space (25%) than during normal flow, whereas the distribution spaces for total and intracellular water remained unaltered. The distension of the vascular tree was confirmed by electron microscopy, by which occasional isolated foci of widened intercellular recesses and spaces of Disse were observed. Cellular ultrastructure was otherwise unchanged, and there was no difference found between normal and retrograde perfusion for bile flow rates, AST release, perfusion pressure, oxygen consumption and metabolic removal of ethanol, a substrate with flow-limited distribution, which equilibrates rapidly with cell water (hepatic extraction ratios were virtually identical: normal vs. retrograde, 0.50 vs. 0.48 at 6 to 7.4 mM input concentration). These findings suggest that the functional and metabolic capacities of the liver remain unperturbed during retrograde perfusion, rendering the technique suitable for the investigation of zonal differences in drug-metabolizing enzymes.

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Long-Term Perfusion of Isolated Rat Liver

Cited by 25 publications

References 17 publications

The regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the isolated perfused rat liver.

The regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the isolated perfused rat liver.

Differential Effects of Fasting and Nicotinic Acid on Various Enzymatic Activities of the 9,000 <i>g</i> Fraction of the Perfused Rat Liver

The multiple-indicator dilution technique for characterization of normal and retrograde flow in once-through rat liver perfusions†

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