Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ISOLATION PERFUSION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed1982

Fluid Exchange in the isolated perfused lung.

The advantages of an isolated, perfused lung preparation in studies of transvascular fluid shifts are described. We find the permeability characteristics of the exchange vessels in the rabbit lung preparation to be similar to those obtained in lungs in situ. The filtration coefficient is similar during plasma and during Krebs-Ringer dextran T 70 perfusion. Therefore proteins in the perfusate do not modify the permeability of the exchange vessels in these lungs as had been reported for other vascular beds. Interstitial fluid pressure in both the alveolar walls and the alveolar corner regions increases with a rise in alveolar pressure. The result is a reduction in the fluid filtration rate under both zone-III and zone-I conditions. The resistance of the extravascular pathway and the fluid pressure in the periarterial/perivenous spaces both appear to be reduced when lung volume is increased by a reduction in pleural pressure. The net effect of positive airway pressure on the transvascular fluid exchange will depend on the relative contribution of the alveolar pressure effects and the lung volume effects. Fluid reabsorption can be observed to occur in the isolated, perfused rabbit lung. This reabsorption does not take place at the level of the loose perivascular tissue spaces since the interstitial fluid pressure at these sites is much lower than the microvascular pressure. We suggest that fluid reabsorption takes place at the thick part of the air-blood barrier, which, most likely, has a higher fluid pressure.

Albumins↗
PubMed1989

[Isolation perfusion chemotherapy using cisplatin in malignant tumors of the extremities].

Since 1960 isolation perfusion chemotherapy has been performed as a preoperative procedure combined with surgery in 226 patients with malignant tumor of the extremities in our department. In this report we presented the result of isolation perfusion chemotherapy using cisplatin (CDDP) for 27 patients since 1983. The histologic classification of the malignant tumor was osteosarcoma in 17 patients, malignant fibrous histiocytoma (MFH) of bone in 8, and other tumor in 2. The extremity was perfused with CDDP (100 micrograms/ml) for 60 minutes. Of 27 patients, 11 were treated with hyperthermic isolation perfusion. The two-year survival rate of the 15 patients with osteosarcoma was 80%, and that of the 7 patients with MFH of bone 71%. The tumor was microscopically analyzed, and the ratio of necrotic to viable tumor cells was calculated. The degree of tumor necrosis was classified as excellent (greater than or equal to 95%), good (80-94%), fair (50-79%), and poor (less than 50%). Of 16 patients, 7 were excellent, 5 good, 3 fair and 1 poor. We concluded that isolation perfusion chemotherapy using CDDP is an effective procedure combined with surgery for malignant tumor of the extremities.

Adolescent↗
PubMed1989

Effect of albumin on the electrophysiologic stability of isolated perfused rabbit hearts.

The electrophysiologic stability of isolated perfused rabbit hearts was evaluated over a period of 5 h. Hearts perfused with protein-free buffer deteriorated over time, with significant shortening of the ventricular effective refractory period (ERP) and development of ventricular fibrillation. When serum albumin (6.01 x 10(-4) mM) was added to the perfusate, hearts were more stable, the ventricular ERPs remained relatively constant throughout the 5-h perfusion period, and hearts did not fibrillate. When a fatty acid-free protein source was used, the hearts demonstrated similar stability to those perfused with protein containing fatty acids. Despite marked changes in the refractory periods of hearts perfused with protein-free buffer, the QRS interval did not change over time, indicating that this is a very insensitive parameter for monitoring the electrophysiologic stability of isolated perfused hearts. In studies utilizing isolated hearts to evaluate antiarrhythmic drug effects, it is preferable to use a protein-containing buffer.

Albumins↗
PubMedDate not supplied

Metabolism of the human carcinogen, benzidine, in the isolated perfused rat liver.

14C-Benzidine (BZ) was added to the recirculating perfusate of the isolated perfused rat liver. The system was monitored at timed intervals for the disappearance of BZ and the appearance of metabolites. BZ was extensively metabolized by this system and after 2 hr of perfusion greater than 95% of the administered radiolabel was in the form of metabolic products. In the perfusate the concentration of BZ declined rapidly whereas the concentration of N-acetyl-BZ (ABZ) increased temporarily and then declined. The concentration of N,N'-diacetyl-BZ (DABZ) increased with time and by 1 hr DABZ had become the major metabolite in the system. In the bile, which contained 22% of the dose after 2 hr, BZ-N-glucuronide and ABZ-glucuronide were the major metabolites initially, but after 1 hr of perfusion N-hydroxy-DABZ-glucuronide had become the major biliary metabolite. Addition of BZ and 35S-Na2SO4 to the perfusate resulted in at least one 35S-containing metabolite. Other major metabolites excreted in bile included 3-hydroxy-DABZ glucuronide, ABZ, and DABZ. DABZ underwent deacetylation to ABZ and N-hydroxy-DABZ underwent rapid reduction to DABZ when added to the isolated liver system. Qualitatively similar biliary metabolite patterns at later times were observed when either BZ, DABZ, or N-hydroxy-DABZ was added to the perfusate.

Animals↗
PubMed1981

The metabolism and excretion of styrene oxide-glutathione conjugates in the rat and by isolated perfused liver, lung and kidney preparations.

The metabolism and excretion of styrene oxide-glutathione conjugates were studied in the intact rat and by isolated perfusion techniques in rat lung, liver and kidney. The intact animals converted the styrene oxide-glutathione conjugates almost entirely to styrene oxide-n-acetylcysteine derivatives mercapturic acids), with much smaller amounts of cysteine, cysteinylglycine and (unchanged) glutathione conjugates. Only small amounts of biliary excretion (approximately 5%) and less than 1% of fecal excretion of radioactivity were found. The isolated perfused kidney retains the capacity to transform virtually all of the glutathione conjugates at the dose level studied (25-30 mumol/kidney) and the principal component in urine from the isolated kidney was the cysteine conjugate. Isolated perfused lung experiments demonstrated that this organ has a minor role in styrene oxide-thioether conjugate. Isolated perfused lung experiments demonstrated that this organ has a minor role in styrene oxide-thioether conjugate metabolism. The isolated perfused liver experiments showed that phenobarbital pretreatment has little effect on biliary excretion but barbital pretreatment has little effect on biliary excretion but that it causes profound qualitative and quantitative effects on metabolism of styrene oxide-glutathione conjugates in the perfusion medium. The high level of styrene oxide-cysteine conjugates in the perfusion medium of an isolated perfused liver, especially after phenobarbital treatment, is consistent with the theory that gamma-glutamyltransferase activity is extracellular. The high-pressure liquid chromatography system of analysis described offers the ability to simultaneously separate and quantitate the major thioether conjugates of styrene oxide and other electrophilic epoxides.

Animals↗
PubMedDate not supplied

Ultrastructure and intercellular vacuolization of isolated perfused and control rat testes.

Isolated rat testes perfused in closed circuit with albuminated Krebs-Ringer bicarbonate buffer were examined by light and electron microscopic techniques in order to assess the structural integrity of the model. The extent of intercellular vacuolization in perfused testes was similar to that of control testes that had been prepared for electron microscopy by routine methods of perfusion fixation. The isolated perfused testes exhibit excellent preservation at the light and electron microscope level. The results indicate that albuminated Krebs-Ringer bicarbonate buffer is an excellent perfusate for in vitro studies of the isolated rat testis. This model of perfused testis can be used to study the early pathology of the effects of toxic compounds on the microscopic anatomy of the male gonad.

Animals↗
PubMed1993

Involvement of endothelium-derived relaxing factor in the pressure control of renin secretion from isolated perfused kidney.

Using isolated rat kidneys perfused at controlled pressure, we examined a potential role of endothelium-derived relaxing factor (EDRF) in the pressure control of renin secretion. We found that stimulation of EDRF release by acetylcholine (1 mumol/liter) increased mean perfusate flow rates from 15.0 +/- 0.5 to 18.0 +/- 0.5 ml/min per g and average renin secretion rates from 3.5 +/- 0.5 to 16.0 +/- 2.0 ng angiotensin I/h per min per g at a perfusion pressure of 100 mmHg (mean +/- SEM, n = 6). Those effects of acetylcholine were significantly reduced during inhibition of EDRF formation with NG-nitro-L-arginine (100 mumol/liter), but they were not affected with the cyclooxygenase inhibitor indomethacin (10 mumol/liter). Lowering of the perfusion pressure from 100 mmHg to 40 mmHg resulted in an increase of average renin secretion rates from 3.5 +/- 0.5 to 79 +/- 12 ng AngI/h per min per g under control conditions (n = 8), and to 171 +/- 20 ng AngI/h per min per g in the presence of 10 mumol/liter acetylcholine (n = 3). The rise of renin secretion in response to a reduction of the renal artery pressure was markedly attenuated with inhibitors of EDRF formation such as NG-nitro-L-arginine (100 mumol/liter) and related compounds. During inhibition of EDRF formation, addition of sodium nitroprusside (10 mumol/liter) increased mean perfusate flow rates from 12.0 +/- 0.5 to 23.0 +/- 2.0 ml/min per g and average renin secretion rates from 2.0 +/- 0.5 to 18.0 +/- 1.5 ng AngI/h per min per g at 100 mmHg (n = 5). Lowering of the perfusion pressure from 100 mmHg to 40 mmHg under those conditions increased average renin secretion rates to 220 +/- 14 ng AngI/h per min per g (n = 5). Taken together, our findings suggest that EDRF and related activators of soluble guanylate cyclase stimulate renin secretion from isolated kidneys, predominantly at lower perfusion pressure. Moreover, pressure control of renin secretion appears to require the tonical stimulation by intrarenal EDRF.

Acetylcholine↗
PubMedDate not supplied

Correlation of 14C-griseofulvin metabolism in rat liver microsomes, isolated perfused rat livers, and in rats with bile duct cannulas.

The metabolism of 14C-griseofulvin has been compared in rat liver microsomes, isolated perfused rat livers, and rats with bile duct cannulas. In all three preparations, 4-desmethylgriseofulvin and 6-desmethylgriseofulvin were the major metabolites. The ratio of total 4-desmethylgriseofulvin to 6-desmethylgriseofulvin formed was 1.20, 0.89, and 1.01 in liver microsomes, isolated perfused livers, and rats with bile duct cannulas, respectively. After a 7-min incubation with liver microsomes, most (96%) of the griseofulvin remained unchanged. Only small amounts of 4-desmethylgriseofulvin (1.26%) of dose) and 6-desmethylgriseofulvin (1.05% of dose) were formed. In isolated perfused liver, most of the drug (59% of dose) was excreted into bile within 4 hr, primarily as 4-desmethylgriseofulvin (24% of dose) and 6-methylgriseofulvin (24% of dose). In animals with bile duct cannulas, 65% of the dose was excreted into bile and 18% of the dose into urine within 4 hours. In bile, 32% of the dose was excreted as 4-desmethylgriseofulvin and 20% of the dose as 6-desmethylgriseofulvin, whereas in urine the drug was excreated predominantly as 6-desmethylgriseofulvin (13% of dose) with only a small amount of 4-desmethylgriseofulvin (1% of dose), during the first 4 hr. These results show that there is good correlation in the metabolic fate of 14C-griseofulvin in the liver microsomes, isolated perfused liver, and rats with bile duct cannulas. In addition to the similar ratio of 4-desmethylgriseofulvin to 6-desmethylgriseofulvin, there is also an agreement in the extent of metabolism and biliary excretion in isolated perfused liver and in rats with bile duct cannulas, which suggests that the isolated perfused liver is an important technique for studying drug metabolism in animals.

Animals↗
PubMed1985

Improved tissue perfusion during pressure regulated hyperthermic regional isolated perfusion. A clinical study.

In previous studies on isolated hindlimb perfusions in dogs, the authors proved that the extracorporeal circuit should be regulated at a delta pressure (systemic mean arterial pressure minus hindlimb mean arterial pressure) of not more than 15 mmHg, to achieve adequate tissue perfusion. To confirm this in patients the authors performed clinical perfusions, divided into three groups. In group I and II the extracorporeal circuit was regulated at a delta pressure of 15 mmHg and 50 mmHg, respectively. In group III perfusions were performed using the common technique of a predetermined fixed flow. Tissue oxygenation, determined by means of a transcutaneous pO2 electrode, was adequate in group I and was severely impaired in group II and III. Although in group I high perfusion flows were needed, leakage was less than 10%. To achieve adequate tissue perfusion during clinical regional perfusions, the extracorporeal circuit must be regulated at a delta pressure of 15 mmHg.

Adult↗
PubMed1991

Aldosterone metabolism in combined isolated perfused rat liver and kidney.

The metabolism of aldosterone (Aldo) at 4 nM was studied by radioimmunoassay and by high-performance liquid chromatography in isolated perfused liver (IPL), isolated perfused kidney (IPK), and combined isolated perfused liver and kidney (CIPLK) of male Wistar rats. Effect of D[4-(14)C]aldosterone (D [4-(14)C]Aldo) on the function of IPK of intact and adrenalectomized (ADX) rats was also studied. Aldo clearance in the liver was most important, 16.3 +/- 1.7 ml/min. In IPK, the total clearance of Aldo was 0.27 +/- 0.36 ml/min (39% of the glomerular filtration rate) (GFR). Fractional excretion (FE) of Aldo was 16 +/- 8%. Metabolic clearance of Aldo was (0.21 +/- 0.23 ml/min), 78% of total renal clearance. In CIPLK, the kidney inhibited hepatic clearance of Aldo by 23% when compared with IPL (P less than 0.05). Hepatic Aldo metabolites were predominantly eliminated by biliary excretion of polar metabolites. Several hepatic polar metabolites and tetrahydroaldosterone (THA) accumulated in perfusate and were excreted in the urine in a similar pattern. After hydrolysis of the polar metabolites, some coeluated with THA and dihydroaldosterone (DHA), whereas other metabolites remained more polar than Aldo. Without addition of Aldo, in IPK of ADX rats FENa was higher (P less than 0.01), and FEK was lower (P less than 0.01), resulting in three- to fourfold higher urinary Na-K ratio (P less than 0.01) when compared with IPK and CIPLK of intact rats. In IPK of ADX rats with Aldo in perfusate, only FEK was restored. Addition of Aldo to IPK of intact rats had no effect. However, only in CIPLK, addition of Aldo resulted in an increasing kaliuresis in three subsequent periods of 30 min (0.56-0.95, P less than 0.01). Thus the hepatic metabolites of Aldo could in part mediate the kaliuretic effect of Aldo.

Adrenalectomy↗
PubMed1984

Metabolic blocker-induced cell damage in rat cardiac tissue. Comparison of three models currently used: the isolated perfused heart, heart cell cultures and isolated myocytes.

In a comparative study on metabolic blockade-induced cardiac cell damage, three different heart (cell) preparations are exposed to potassium cyanide (KCN) and iodoacetamide (IAA) in fixed concentrations (5 and 0.1 mmol/l, respectively). The preparations used are the perfused rat heart, isolated rat heart myocytes and rat heart cell cultures. Irreversible heart cell damage is reflected by the release of a cytoplasmic enzyme, LDH (lactate dehydrogenase), or HBDH (alpha-hydroxybutyrate dehydrogenase) from the heart (cell) preparations. Metabolic blockade-induced release of 50% of the originally intracellularly located LDH or HBDH is reached after 2-3 h from rat heart cell cultures, after 2-4 h from isolated rat heart myocytes and after variable (coronary flow-dependent) durations of perfusion from perfused rat hearts. It is concluded that to study the effect of toxic agents on myocytic integrity, the use of isolated cardiac myocytes and heart cell cultures is preferable to the use of isolated perfused hearts.

Animals↗
PubMed1987

The metabolism of oestrone and some other steroids in isolated perfused rat and guinea pig livers.

1. Oestrone is rapidly taken up by isolated perfused rat liver (t 1/2 less than 2 min) to yield at least 10 metabolites excreted in the bile; peak concentration occurs after about 20 min. 2. Sulphated metabolites of oestrone appear in the perfusate, reaching peak concentration at about 10 min, and then slowly disappear. 3. Sulphated metabolites of oestrone accumulate in the liver during the first 10 min. They are partly converted to sulphoglucuronides (steroid 3-sulphates conjugated with glucuronic acid in the D ring) and partly hydrolysed to be reconjugated as glucuronides. 4. The major biliary metabolites of oestrone in isolated perfused rat liver are glucuronides and sulphoglucuronides, but free steroids, sulphates and polar metabolites are also so excreted. 5. The isolated perfused guinea pig liver also rapidly takes up oestrone (t 1/2 less than 2 min) but, in contrast to the rat, a single glucuronide is the only quantitatively important metabolite in the bile: it is also extensively secreted into the perfusate where it reaches peak concentration at about 10 min. 6. In perfused guinea pig liver, oestrone does not form sulphoglucuronides, and sulphates are only minor metabolites; this is not due to lack of the appropriate sulphotransferase because oestradiol 17 beta-(beta-D-glucuronide) is extensively sulphated in this system. 7. Oestradiol 17 beta-(beta-D-glucuronide) is not cholestatic in the isolated perfused guinea pig liver although it is in rat liver. 8. There is a similar species difference in the metabolism of dehydroepiandrosterone in the two species: the rat forms sulphoglucuronides, the guinea pig does not. 9. The perfused rat liver extensively hydroxylates, presumably on the D ring, 17-deoxyoestrone and 17-deoxydehydroepiandrosterone. 10. The inability of perfused guinea pig liver to form sulphoglucuronides from oestrone or dehydroepiandrosterone is probably due to its restricted ability to hydroxylate the D ring of steroids. 11. Both rat and guinea pig biles contain beta-glucuronidase, about 80 and 230 sigma units/ml, respectively.

Animals↗
PubMed1981

Differential scanning calorimetry and fluorescence probe investigations of very low density lipoprotein from the isolated perfused rat liver.

Isolated rat livers were perfused at 37 degrees C with blood-free, defined medium containing delipidized bovine serum albumin (BSA), BSA-oleate, or BSA-palmitate. Very low density lipoproteins (VLDL) were isolated from the perfusate at 12 degrees C and lipid components were extracted and purified. Differential scanning calorimetry indicated multiple phase alterations in intact VLDL. The extracted triglycerides exhibited phase alterations at similar temperatures as the intact VLDL. The small quantities of cholesteryl esters present in the VLDL generally did not greatly affect the VLDL triglyceride transitions. The extracted phospholipids showed detectable transitions that were abolished by cholesterol at mole ratios found in the respective VLDL. The phase behavior of VLDL and its component triglycerides was associated with the degree of unsaturation of the infusate fatty acid, and by variation of fatty acid chain length. The structural differences between VLDL lipid fractions noted by DSC were also monitored by fluorescence probes. The data indicated that in the intact VLDL the physical properties of the 'interior core' lipids can affect the properties of the 'surface monolayer'. In addition, Arrhenius plots of corrected fluorescence indicated that trans-parinarate and diphenyl-hexatriene detected different characteristic breakpoint temperatures in the phospholipids. The breakpoints of triglycerides were highly dependent on the type of fatty acid in the infusate, but were similar to those noted in intact VLDL. Finally, the breakpoints in Arrhenius plots of fluorescence probe parameters did not necessarily coincide with onset or end temperatures of DSC transitions.

Animals↗
PubMed1992

Effect of angiotensin II-induced changes in perfusion flow rate on chlorothiazide transport in the isolated perfused rat kidney.

Angiotensin II was used as a probe to study the effect of changes in perfusate flow rate on the renal clearance parameters of chlorothiazide in the isolated perfused rat kidney. Perfusion studies were performed in five rats with no angiotensin II present in the perfusate and in five rats with a 1-4 ng/min infusion of angiotensin II into the perfusate. Angiotensin II had a dramatic effect on the renal hemodynamics, resulting in a 43% decrease in perfusate flow, a 16% decrease in glomerular filtration rate (GFR), and a 45% increase in filtration fraction. Values for the fractional excretion of glucose were low and consistent, with or without angiotensin II. Although the unbound fraction (fu) of chlorothiazide was unchanged between treatments, the renal (CLr) and the secretion clearances were reduced by about 50% in the presence of angiotensin II; the excretion ratio [ER = CLr/(fu.GFR)] was reduced by 38% with angiotensin II present in the perfusate. Analysis of the data was complicated by the presence of a capacity-limited transport for renal tubular secretion. Transport parameters (+/- SD) were obtained and the corrected intrinsic secretory clearance [(Vmax/GFR)/Km] of chlorothiazide was 123 +/- 18 without angiotensin II vs. 72.8 +/- 30.0 with angiotensin II. These results demonstrate that alterations in organ perfusion can significantly reduce the clearance parameters of chlorothiazide in the rat IPK. These flow-induced changes in intrinsic secretory transport may reflect perturbations other than that of perfusion flow rate alone.

Angiotensin II↗
PubMed1996

High-pressure liquid chromatographic assay for the determination of thyrotropin-releasing hormone and its common metabolites in a physiological salt solution circulated through the isolated perfused rat lung.

A specific and sensitive assay for TRH (L-pyroglutamyl-L-histidyl-L-proline amide), 3H-TRH (L-proline 3,4-3H(N), histidyl-3-3H(N)), and four possible metabolites of TRH, present in the recirculated perfusate of an isolated perfused rat lung preparation, was developed. Unlike previous methods, the method developed does not require extraction of the analytes from the biological matrix. The crude sample was adjusted to a pH of 3.2 with concentrated trifluoroacetic acid and injected on to a PRP-1 (polystyrene divinylbenzene) column (10 microns, 25 cm x 4.6 mm i.d.). The mobile phase was 10% v/v acetonitrile and 90% v/v 0.75 g l-1 1-hepantanesulfonic acid in 0.004 M trifluoroacetic acid, adjusted to a pH of 2.4 with concentrated NaOH. The flow rate was 0.5 ml min-1 and the analytes were detected by UV absorption at a wavelength of 26 nm and by radiochemical detection utilizing a liquid scintillation counter. The nominal retention times for L-PRO, L-PRO-NH2, TRH, cyclo(HIS-PRO) and TRH-OH were 4.0 +/- 0.9, 10.0 +/- 0.2, 15.5 +/- 0.4, 19.2 +/- 0.5 and 25.3 +/- 0.5 min respectively. The assay performs well in terms of precision and accuracy as indicated by linear regression and intra-assay variability analysis.

Animals↗
PubMed1999

Peptidoleukotriene (PLT) release and absorption from the airways of the isolated perfused guinea pig lung following chemical and antigenic challenge.

PURPOSE: To study the release and absorption of peptidoleukotrienes (PLTs) from the airways of the guinea pig lung following calcium ionophore A23187 (CI), benzalkonium chloride (BAC), ethylene diamine tetra-acetic acid (EDTA) or ovalbumin (OA) challenge. METHODS: PLT C4/D4/E4 were quantified in the perfusate of the isolated perfused guinea pig lung (IPGPL) following intratracheal administration of CI, BAC, EDTA or OA in different doses. The formation and airway-to-perfusate transfer kinetics of PLTs were analyzed by fitting mean data for cumulative PLT in perfusate vs. time to an A-->B-->C first-order release and transfer model, with dose-dependent transfer rate constants. RESULTS: CI induced apparent first order release of PLTs with a t1/2 approximately equal to 1.2 minutes. The amount of PLT released was CI dose-dependent, as was the airway-to-perfusate transfer rate constant. These reached maxima of 0.254 microgram and 0.0557 min.-1, respectively, around a CI dose of 100 micrograms. In OA-sensitized IPGPL preparations, OA induced a similar dose-dependent release of PLTs, although the rates of PLT release were much greater and more variable than those seen with CI. In OA sensitized IPGPL preparations, at an OA dose of 1000 micrograms, the maximum amount of PLT released was 0.289 micrograms and the maximal airway-to-perfusate transfer rate constant was 0.0229 min-1. BAC and EDTA failed to induce quantifiable PLT release from the airways. CONCLUSIONS: Rapid release of the inflammatory mediators, PLT C4/D4/E4, could be induced in the unsensitized IPGPL by CI, and in the sensitized IPGPL by OA. Transfer into perfusate occurred in both cases with dose-dependent t1/2 ranging from 12.4 through 57.8 minutes.

Absorption↗
PubMed1977

Synthesis and release of low density lipoproteins by the isolated perfused pig liver.

In previous studies, we have shown that a relatively large amount of low density lipoproteins is released into the perfusate during isolated pig liver perfusion. The present studies were done to determine the source of these lipoproteins. Breakdown of the very low density lipoproteins to low density lipoproteins by the perfusion apparatus or by hepatic catabolism was excluded by adding 125I very low density lipoproteins to the perfusate in the presence and absence of a liver and then measuring the radioactivity in the low density lipoprotein fraction after rate-zonal ultracentrifugation. Release of preformed low density, lipoproteins from the liver was investigated by injecting iodine-labeled low density lipoproteins in vivo several hours prior to perfusion of the liver and then measuring the release of labeled low density lipoproteins into the perfusate. It was shown that intact labeled low density lipoproteins were released by the perfused liver. De novo synthesis of the low density lipoproteins was established by measuring the incorporation of [1-14C]leucine into this lipoprotein fraction. The radioactivity in the low density lipoprotein fraction increased with time and accounted for 20 to 25% of the total radioactivity incorporated into all the lipoprotein fractions. The incorporation of [1-14C]leucine into the low density lipoproteins was confirmed by rate-zonal analysis. We conclude that the low density lipoproteins in the perfusate from pig liver perfusions were derived mainly from a preformed liver pool, but also partly from de novo synthesis by the liver.

Animals↗
PubMedDate not supplied

Metabolism and choleretic effect of naltrexone in the isolated perfused rat liver.

A specific high-pressure liquid chromatographic assay was developed for the measurement of the narcotic antagonist drug, naltrexone. When 10 mg of naltrexone . HCl was added to the perfusate of the isolated perfused rat liver, the concentration of the drug in the perfusate declined rapidly with an apparent half-life of about 9 min. At 30 min 90% of the unchanged drug had been removed from the perfusate; the liver at this time retained 47% of the total radioactivity, of which only 75 represented unchanged drug. The bile at 30 min contained 28% of the total radioactivity and by 120 min this had risen to 70%. Initially naltrexone glucuronide was the principal metabolite in the bile. After 60 min N-dealkylated naltrexone glucuronide was the principal metabolite in bile. A marked increase in bile flow was noted immediately after the addition of the drug to the perfusate. The choleretic effect was attributed to the osmotic effect of the metabolites of naltrexone in the bile.

Animals↗