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 577 records · Page 32Linked to original sources
PubMed1988

Radioimmunoassay for rat pancreatic alpha-amylase and the effect of Phe-Met-Arg-Phe-amide on amylase secretion in the isolated perfused rat pancreas.

In this study a radioimmunoassay was developed to measure secreted amylase from the isolated perfused rat pancreas. Using Sephadex G-75 gel chromatography, rat pancreatic amylase was purified to a single migrating protein band as determined by SDS polyacrylamide gel electrophoresis. Specificity of a rat pancreatic amylase antiserum, raised in rabbits, was determined using immunodiffusion, immunoelectrophoresis, and immunoblotting techniques. Secreted amylase concentrations, obtained using the radioimmunoassay, were not significantly different than those measured with the amylase enzyme assay. The rat pancreatic amylase radioimmunoassay was used to measure the amylase secretion in the isolated perfused rat pancreas. Phe-Met-Arg-Phe-amide (FMRF-NH2) immunoreactivity has been shown to be co-localized with pancreatic polypeptide in the rat pancreatic islet, and evidence suggests that islet peptides modulate amylase secretion from the exocrine pancreas. In the present study, FMRF-NH2 significantly (p less than 0.05) suppressed cholecystokinin (CCK)-stimulated amylase secretion by 55%. The average pancreatic amylase secretion in response to CCK was 10.89 +/- 2.0 micrograms/ml/min (n = 6); with the addition of FMRF-NH2, CCK-stimulated amylase secretion was reduced to 4.79 +/- 1.6 micrograms/ml/min (n = 6). These results are consistent with the insuloacinar hypothesis in that an FMRF-NH2-like substance in the islet may act to modulate the exocrine pancreas.

Animals↗
PubMed1987

Xanthine oxidase is not responsible for reoxygenation injury in isolated-perfused rat heart.

The massive leakage of intracellular enzymes which occurs during reoxygenation of heart tissue after hypoxic or ischemic episodes has been suggested to result from the formation of oxygen radicals. One purported source of such radicals is the xanthine oxidase-mediated metabolism of hypoxanthine and xanthine. Xanthine oxidase (O form) has been suggested to be formed in vivo by limited proteolysis of xanthine dehydrogenase (D form) during the hypoxic period (Granger et al., Gastroenterology, 81, 22 (1981)). We measured the activities of xanthine oxidase in both fresh and isolated-perfused (Langendorff) rat heart tissue. Approximately 32% of the total xanthine oxidase was in the O form in fresh and isolated-perfused rat heart. This value was unchanged following 60 min of hypoxia and 30 minutes of reoxygenation. The infusion of 250 microM allopurinol throughout the perfusion completely inhibited xanthine oxidase activity but had no effect on the massive release of lactate dehydrogenase (LDH) into the coronary effluent upon reoxygenation of heart tissue subjected to 30 or 60 min of hypoxia. Protection from 30 min of hypoxia was also not obtained when rats were pretreated for 48 h with allopurinol at a dose of 30 mg/kg/day and perfused with allopurinol containing medium. Superoxide dismutase (50 units/ml), catalase (200 units/ml), or the antioxidant cyanidanol (100 microM) also had no effect on LDH release upon reoxygenation after 60 min of hypoxia. Xanthine oxidase activity was detected in a preparation enriched in cardiac endothelial cells while no allopurinol-inhibitable activity could be measured in purified isolated cardiomyocytes. It is concluded that xanthine dehydrogenase is not converted to xanthine oxidase in hypoxic tissue of the isolated perfused rat heart, and that the release of intracellular enzymes upon reoxygenation in this experimental model is mediated by factors other than reactive oxygen generated by xanthine oxidase.

Allopurinol↗
PubMed1987

The biosynthesis of 2-guanidinoethanol in intact mice and isolated perfused rabbit kidneys.

The metabolic pathway for the synthesis of 2-guanidinoethanol (GEt) was studied in intact mice and isolated perfused rabbit kidneys. GEt excretions in 24-hr urine increased after the intraperitoneal injection of ethanolamine (EA) into mice. Perfusion of isolated rabbit kidneys with EA and L-arginine (Arg) enhanced the GEt excretion from the ureter. This enhancement was observed in an EA concentration-dependent manner under the presence of Arg. When glycine (Gly) was added to the perfusion medium together with EA and Arg, the enhancement of GEt excretion was inhibited, whereas, guanidinoacetic acid excretion was increased to the same extent as during the perfusion with Gly and Arg. These results indicate that GEt is synthesized from Arg and EA in the kidney and that this synthesis is catalyzed by Arg:Gly amidinotransferase (EC 2.1.4.1.). We also described the guanidino compound excretion levels, including levels of GEt, in the rabbit, mouse, rat, and cat. The levels varied considerably with mammalian species.

Animals↗
PubMed2006

Responsiveness to inhaled NO in isolated-perfused lungs from endotoxin-challenged rats is dependent on endogenous nitrite/nitrate synthesis.

BACKGROUND AND OBJECTIVES: In isolated-perfused lungs of lipopolysaccharide (LPS)-challenged rats, vasodilatation to inhaled nitric oxide (NO) is impaired. Inhibition of nitric oxide synthase 2 (NOS2) by aminoguanidine (AG) prevented hyporesponsiveness to inhaled NO. Here, we investigated whether NOS2-mediated nitrite/nitrate synthesis modulates responsiveness to inhaled NO. METHODS: Sprague-Dawley rats received intraperitoneally 0.5 mg kg(-1) LPS. Four hours later, LPS-treated rats received 3, 10 or 30 mg kg(-1) AG or 0.01, 0.1 or 1 mg kg(-1) S-methylisothiourea (SMT) by intraperitoneal injection. Sixteen to eighteen hours later, lungs were isolated and perfused, and pulmonary artery pressure (PAP) was elevated by 6-8 mmHg using the thromboxane analogue U46619. The decrease of PAP in response to inhaled NO and nitrate/nitrite levels in serum and perfusate was measured. RESULTS: In rats treated with LPS alone or 0.01 or 0.1 mg kg(-1) SMT, 40 ppm NO decreased PAP less than in rats treated with AG and 1 mg kg(-1) SMT (-1.8 mmHg (95% confidence interval: -1.5 to -2.1) vs. -6.0 mmHg (-5.7 to -6.3), P < 0.01). Improved NO responsiveness was associated with lower serum and perfusate nitrite/nitrate levels than in rats with hyporesponsiveness to inhaled NO (102 micromol (82-122) vs. 282 micromol (261-303) and 8.1 micromol (6.9-9.3) vs. 19.8 micromol (17.2-22.4), respectively, P < 0.01). CONCLUSIONS: These observations demonstrate that in isolated-perfused lungs of LPS-treated rats, NOS2 inhibition improved responsiveness to inhaled NO. Here, responsiveness to inhaled NO is dependent on the ability of NOS2 inhibitors to reduce nitrite and nitrate levels in serum and released in the lung.

Administration, Inhalation↗
PubMed1996

Interleukin-6 tumor necrosis factor-alpha clearance and metabolism in vivo and by the isolated, perfused liver in the rat: effect of acute alcohol administration.

Plasma clearance and organ distribution of intravenously injected human recombinant [125I]interleukin (IL)-6 and [125I]tumor necrosis factor (TNF)-alpha were studied in male rats, 2 hr after intravenous alcohol (ethanol) administration (single dose, 2.2 g.kg-1 body weight). Also, the rate of uptake and degradation of the two cytokines by the isolated, perfused rat liver was studied in the absence or in the presence of ethanol (35 mM) in the perfusate. Acute ethanol administration significantly increased plasma clearance rate for both cytokines (36% and 72%, for IL-6 and TNF-alpha, respectively), decreased the t1/2 alpha (30% and 11%, for IL-6 and TNF-alpha, respectively), abolished the slow (beta)-phase component for TNF-alpha, and increased t1/2 beta for IL-6 (31%). Although alcohol did not affect organ distribution of TNF-alpha, it increased the IL-6 content in the liver, kidney, and blood. IL-6 uptake rate by the isolated, perfused rat liver was 2-fold higher than TNF-alpha uptake, whereas the rate of degradation was larger for TNF-alpha than for IL-6, despite the fact that both cytokines were presented to the liver at the same concentration (6 nM). Ethanol addition to the perfusate (35 mM, final concentration) significantly increased TNF-alpha uptake (24%), without affecting IL-6 uptake or the degradation rate of either cytokine. Also, the kinetics of degradation by the isolated, perfused rat liver was linear for TNF-alpha, but exponential for IL-6. Data presented in this study demonstrate that: (1) acute alcohol consumption can alter the kinetic behavior of IL-6 and TNF-alpha in the bloodstream, mainly by accelerating their clearance which, in turn, may counteract the outcome of cytokine secretion and delivery to the blood; and (2) short exposure of liver to ethanol levels commonly seen in humans after binge drinking may alter its capacity to take up cytokines.

Alcoholic Intoxication↗
PubMed1988

Effect of altered albumin concentrations on elimination of unbound prazosin in vivo in the rat and in the isolated perfused rat liver.

Albumin is known to affect the intrinsic clearance of many compounds in the isolated perfused rat liver, but little is known of its effect in vivo. The influence of decreased albumin concentrations on clearance of unbound prazosin and intrinsic clearance of prazosin was therefore studied in vivo in rats that had undergone plasmapheresis. An approximate 30% reduction in the plasma albumin concentration was achieved in animals not given plasma expanders and an approximate 50% reduction was achieved in animals given Ficol 70 as a plasma expander. No differences were seen in the intrinsic clearances or in the clearances of unbound prazosin between control animals and plasmapheretic animals. The reason for this lack of effect is apparent from parallel studies in isolated perfused rat livers. An increase in the clearance of unbound prazosin of 27% was seen when the albumin concentration was increased from 0 to 30 microM, and of 49% when the concentration of albumin was increased to 90 microM, with no further increase at higher albumin concentration. These results, therefore, suggest that changes in the albumin plasma concentrations normally encountered clinically may have little effect on the intrinsic elimination of drugs.

Albumins↗
PubMed1981

Fate of inhaled nitrogen dioxide in isolated perfused rat lung.

The fate of inhaled NO2 was studied with isolated perfused rat lungs. The isolated lungs were exposed to 5 ppm NO2 for 90 min at a ventilation rate of 34 ml/min. The NO2 exposure had no adverse effects on the lungs as judged from their weights, glucose uptake, or lactate production compared to control lungs. Isolated lungs absorbed 36% of ventilated NO2, which was detected in perfusate and lung tissue as NO2- but not NO3-. The NO2- concentration in perfusate increased linearly with time, and after 90 min of ventilation with NO2 and perfusion with erythrocyte-free medium the NO2- accumulation was 6.36 +/- 0.39 micrograms. If perfusate contained 10% erythrocytes, the ventilated NO2 product was mostly NO3- in perfusate but NO2- in lung tissue. Protein solutions absorbed NO2 more effectively than simple salt solutions, but they all yielded mainly NO2- unless erythrocytes were present, when the product was mostly NO3-. The results indicate that absorbed NO2 in the lung is converted predominantly to NO2-, but after its diffusion into the vascular space it is oxidized to NO3- by interactions with erythrocytes.

Absorption↗
PubMed1996

Factors influencing hepatocyte trafficking during allogeneic hepatocyte transplantation: improved liver sequestration with isolated perfusion.

Transplantation of normal or ex vivo modified hepatocytes holds promise in therapy of a variety of diseases. In order to investigate hepatocyte trafficking, and specifically to determine whether the route, method of delivery, or other host factors may affect hepatocyte sequestration in the liver, 51chromium- and 111indium-labeled hepatocytes were transplanted into allogeneic hosts. Systemic injection of hepatocytes into the femoral vein resulted in sequestration mainly in the lungs (30 +/- 4%) whereas sequestration in the liver amounted to only 5 +/- 1%. Portal injection resulted in a dramatic increase in the liver sequestration (52 +/- 4%) and a reduction in the lung (2 +/- 1%, P < 0.05 vs systemic injection). Nevertheless, nearly half of portally injected hepatocytes came to rest in other organ sites. Partial hepatectomy prior to transplantation did not change the total hepatocyte sequestration in the liver or the organ specific activity. A remote site of inflammation, in the form of a turpentine abscess, also did not alter the pattern of hepatocyte trafficking. Isolated perfusion of the liver with labeled hepatocyte, however, significantly increased the sequestration of hepatocytes at this organ (control, 52 +/- 4%; isolated perfusion, 71 +/- 9%; P < 0.05). In the delivery of potentially toxic gene products for therapy, isolated perfusion of the target organ appears to provide the greatest likelihood of restricting expression of potentially toxic gene products to the target organ.

Animals↗
PubMed1995

Immunoglobulin G, F(AB')2, and fab fragment uptake kinetics in isolated perfused rat liver and rat hepatic cells.

The interaction of 125I-radiolabeled immunoglobulin G (IgG), F(ab')2, and Fab fragments with different modes of production (polyclonal or monoclonal), belonging to different subclasses (IgG1 and IgGT) and derived from different sources (mouse, rat, and horse) with liver, was investigated by using isolated perfused rat liver and isolated rat hepatic parenchymal cells (PCs) and non-parenchymal cells (NPCs) in suspension. Lactosaminated-bovine serum albumin (Lac-BSA) and formaldehyde-bovine serum albumin were used as markers of specific binding to PCs and NPCs, respectively. Using the isolated perfused rat liver model, data clearly indicated a very weak hepatic extraction ratio (< 0.003) for IgGs and fragments in comparison with Lac-BSA (extraction ratio = 0.398) over the 3 hr of the experiments. No breakdown or higher molecular weight compounds were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Biliary excretion of IgGs and fragments ranged from 0.07 to 0.3%, mainly as free iodine-125. In contrast, 7% of Lac-BSA was excreted unchanged in bile, and 10% of free iodine was excreted at 3 hr. In vitro binding studies showed no specific binding of any antibody and fragment proteins at 4 degrees C or 37 degrees C. In contrast, saturable uptake was observed for Lac-BSA with PCs and formaldehyde-bovine serum albumin with NPCs. Both models demonstrated that nonspecific antibody/fragment interactions occurred with rat liver. Several hypotheses can be formulated to explain why liver-antibody interactions depend on more complex antibody molecular states (aggregated structure and immune complex) rather than the monomeric structure investigated in the present study.

Animals↗
PubMed1986

Metabolism of hexachlorobenzene (HCB) in the isolated perfused rat liver.

The metabolism of HCB in the isolated perfused rat liver was studied by administration of [14C]HCB diluted with unlabelled HCB at a total dose of 0.1 mg HCB/ml perfusate. Metabolites in bile, perfusate and liver were studied by GLC-mass spectrometry. Histological examination of the livers showed that no hepatic necrosis had developed, although there was a slight increase in ASAT and ALAT in the perfusate and about 50% decrease in hepatic glutathione. About 0.15% of administered radioactivity was recovered in the bile within 2 hr. In the bile, HCB together with the metabolites pentachlorothiophenol and pentachlorophenol, were identified and accounted for about 20% of the radioactivity excreted. In addition, eleven metabolites with 4 or 5 chlorines were isolated. In the perfusate and in the liver, unchanged HCB was responsible for most of the radioactivity. Traces of pentachlorothiophenol and pentachlorophenol were identified in the perfusate and the liver, respectively.

Animals↗
PubMed1991

Studies on secretion of catecholamine evoked by caffeine from the isolated perfused rat adrenal gland.

The influence of caffeine on secretion of catecholamines (CA) was examined in the isolated perfused rat adrenal gland. Caffeine (0.3 mM) perfused into an adrenal vein of the gland produced a marked increase in secretion of CA. This secretory effect of CA evoked by perfusion of caffeine for one minute was considerably prolonged, lasting for more than 90 minutes. The tachyphylaxis to releasing effect of CA induced by caffeine was observed by repeated perfusion of this drug. The caffeine-evoked CA secretion was markedly inhibited by pretreatment with ouabain, trifluoperazine, TMB-8 and perfusion with calcium-free Krebs solution containing 5 mM EGTA, but was not affected by perfusion of calcium-free Krebs solution without other addition. CA secretion evoked by caffeine was not reduced significantly by pretreatment with chlorisondamine but after the first collection of perfusate for 3 min was clearly inhibited. Interestingly, the caffeine-evoked CA secretion was considerably potentiated by pretreatment with atropine or pirenzepine, but after the first collection for 3 min it was markedly decreased. These experimental results suggest that caffeine causes a marked increase in secretion of CA from the isolated perfused rat adrenal gland by an extracellular calcium-independent exocytotic mechanism. The secretory effect of caffeine may be mainly due to mobilization of calcium from an intracellular calcium pool in the rat chromaffin cells and partly due to stimulation of both muscarinic and nicotinic receptors.

Adrenal Glands↗
PubMed1983

Possible prostacyclin-mediated vascular effect of angiotensin II in the isolated perfused rat lung.

Angiotensin I (A I) and angiotensin II (A II) when injected through the pulmonary artery caused an increase in perfusion pressure (PP) of the isolated perfused rat lung and a contraction when the venous outflow was superfused over rat ascending colon (RC). Nicotine (N) when added to the perfusion medium caused a significant increase in PP to A II without altering that to A I. Further addition of ZK 36374, a stable analog of prostacyclin (PGI2), to the medium prevented the potentiating effect of N on the A II pressor response. Neither N nor ZK 36374 altered the superfused RC responses to A I and A II-injected venous effluent. Lysine acetylsalicylate (ASA), however, caused a potentiation in the pressor response to A I. The response of venous effluent superfused RC to A I was also found to be potentiated by ASA. ASA failed to alter the responses to A II. These results were taken as evidence that A II is a potent activator for the biosynthesis of PGI2 in the pulmonary vascular bed. Moreover, PGI2 does not affect angiotensin converting enzyme activity in the lung circulation while other stable metabolites of arachidonic acid can inhibit the conversion of A I to A II.

Angiotensin I↗
PubMed1997

Differential effects of diadenosine phosphates on purinoceptors in the rat isolated perfused kidney.

1. The activation of various purinoceptors in rat renal vasculature by P1,P2-diadenosine pyrophosphate (Ap2A), P1,P3-diadenosine triphosphate (Ap3A), P1,P4-diadenosine tetraphosphate (Ap4A), P1,P5-diadenosine pentaphosphate (Ap5A), P1,P6-diadenosine hexaphosphate (Ap6A) was studied by measuring their effects of perfusion pressure of a rat isolated perfused kidney. 2. The vasoconstrictive response to Ap5A was completely due to P2x purinoceptor activation, that to Ap4A and Ap6 was P2x purinoceptor mediated to a large extent, as evidenced by the inhibitory effects of suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (PPADS). 3. The vasoconstrictive effects of Ap2A and Ap3A were mostly due to stimulation of A1-receptors, as shown by the inhibitory effect of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). 4. The vasoconstrictive response to Ap6A was partially insensitive to A1 and P2x purinoceptor blockers. 5. In raised tone preparations Ap2A and Ap3A evoked vasodilatation, which was blocked by the A2 receptor blocker, 3,7-dimethyl-1-propargylxanthine (DMPX). 6. In raised tone preparations Ap4A evoked vasodilatation when the P2-purinoceptors were blocked by suramin. 7. The activation of different purinoceptor subtypes by diadenosine phosphates critically depends on the number of phosphate groups.

Adenosine↗
PubMedDate not supplied

Mechanisms of lidocaine kinetics in the isolated perfused rat liver. II. Kinetics of steady state elimination.

The steady state kinetics of lidocaine and its metabolites were modeled using nonlinear elimination pathways for multiple enzymes. The main metabolites, monoethylglycinexylidide and 3-hydroxy-lidocaine, were infused in the absence of lidocaine to measure the kinetic parameters for secondary elimination. Data from continuous perfusion of lidocaine in the isolated perfused rat liver at concentrations ranging from 9.6 to 278 microM (N = 16) were used to calculate the kinetic parameters for formation of the main metabolites. The elimination of lidocaine in the liver was approximated by the well stirred model. The whole liver study gave higher elimination rates than were predicted from microsomal studies. The major pathways for elimination of lidocaine in the rat were deethylation and hydroxylation, and subsequent elimination along these pathways accounted for the poor material balance at low dosage levels. The observed competitive inhibition of hydroxylation was in agreement with the predictions of the model.

Animals↗
PubMed1990

Basal prostaglandin synthesis by the isolated perfused rat kidney.

In order to assess the main characteristics of the prostaglandin (PG) biosynthesis by the isolated perfused rat kidney, the urinary and venous outputs of PGE2, PGF2alpha, 6-keto-PGF1alpha and of thromboxane (Tx)B2 were followed during 120 min after an equilibration period of 30 min. Single pass kidneys were perfused with a Krebs-Henseleit solution added with Polygeline at a constant flow rate providing a perfusion pressure about 90 mm Hg. From the beginning of the study, major differences could be observed in the renal biosynthetic rate of the 4 PG studied which were mainly excreted into the venous effluent. During the perfusion, urinary and venous outputs of PGE2, PGF2alpha and of TxB2 remained stable whereas those of 6-keto-PGF1alpha sharply increased and were found inversely related to the glomerular filtration rate (r = -0.95; p n 0.001). Finally, the urinary and venous outputs of each of the four PGs studied were found positively related. It is concluded that the isolated perfused rat kidney is a valuable preparation for studying the biosynthesis of PGs and that, at least in thi model, the urinary excretion of PGs is a good index of their renal synthesis.

Animals↗
PubMed1996

Effects of nitric oxide on hyperinflation-induced pulmonary hypertension in the isolated-perfused lung.

OBJECTIVE: To determine if nitric oxide decreases pulmonary vascular resistance in hyperinflation-induced pulmonary hypertension. DESIGN: Isolated-perfused lamb lung model. SETTING: Experimental animal laboratory in a university setting. SUBJECTS: Ten isolated-perfused lamb lungs harvested from subjects with a mean age of 29 days. INTERVENTIONS: After induction of anesthesia, endotracheal intubation, and mechanical ventilation, lungs were perfused via an extracorporeal circuit. Ventilatory pressures were set to provide tidal volumes of 10 mL/kg and ventilatory rates were adjusted to maintain a Paco2 of 40 +/- 5 torr (3.5 +/- 0.7 kPa). The perfusion system consisted of a blood reservoir, a membrane oxygenator, and a nonocclusive roller pump. Blood flow was increased progressively to 50 mL/kg/min, maintaining a pulmonary arterial pressure of < 25 mm Hg and a left atrial pressure between 2 and 5 mm Hg. End-expiratory lung volume was measured using a nitrogen washout method. Baseline data were collected after a 1-hr stabilization period. Lung volume was increased to achieve 25% (moderate hyperinflation) and 50% (severe hyperinflation) increments in pulmonary vascular resistance. Nitric oxide (80 parts per million) was administered to the preparation after each increment in lung volume. MEASUREMENTS AND MAIN RESULTS: Mean pulmonary arterial pressure, mean left atrial pressure, pulmonary vascular resistance, and static lung compliance were measured at baseline and after moderate and severe hyperinflation, both before and after nitric oxide administration. Significant decreases in pulmonary vascular resistance were found when the preparation was ventilated with nitric oxide at baseline (43% decrease) and during hyperinflation induced pulmonary hypertension at both moderate (31% decrease) and severe (23% decrease) levels of hyperinflation. CONCLUSIONS: Inhaled nitric oxide significantly reduces pulmonary vascular resistance, even when pulmonary hypertension is induced by airway hyperinflation and supraphysiologic lung volumes. These data suggest that the use of nitric oxide following lung transplantation may allow for effective management of pulmonary hypertension in patients who receive allografts from undersized donors. Further clinical experience will be crucial in precisely defining the range of donor-recipient size mismatch that can be adequately managed and the time course over which nitric oxide can be administered safely and effectively to these patients.

Animals↗
PubMed1996

Folate transport pathways regulate urinary excretion of 5-methyltetrahydrofolate in isolated perfused rat kidney.

The reabsorption of 5-methyltetrahydrofolic acid (5-CH3-H4PteGlu) by the renal proximal tubule has an important role in the maintenance of plasma folate concentrations. However, the mechanism by which this vitamin traverses the renal epithelium remains to be determined. Studies in cultured cells have suggested that the folate receptor in association with a probenecid-sensitive anion carrier may be involved in the transmembrane transport of the vitamin. Because 5-CH3-H4PteGlu is reabsorbed and metabolized in the isolated perfused rat kidney (IPRK) in a smaller manner to in vivo models, the IPRK was used to evaluate pathways involved in folate reabsorption. Reabsorption of 5-CH3-H4PteGlu could not be saturated in the isolated perfused rat kidney, even at concentrations up to 2 mumol/L. Folic acid (PteGlu) was used as a competitive inhibitor of FR-dependent reabsorption of 5-CH3-H4PteGlu. When 5-CH3-H4PteGlu was maintained at 1 nmol/L (a concentration at which receptor-mediated transport should be maximal), PteGlu (up to 100 nmol/L) had no effect on reabsorption. The addition of probenecid (1 mmol/L) did not affect the reabsorption of 5-CH3-H4PteGlu but inhibited the fractional excretion of the anion para-aminohippurate. Probenecid also inhibited the urinary excretion of 5-CH3-H4PteGlu metabolites, indicating that reabsorbed 5-CH3-H4PteGlu was metabolized to products that were subsequently secreted into the urine by anion exchange pathways. The physiological importance of a folate receptor-mediated reabsorption of 5-CH3-H4PteGlu appears to be minor in the isolated perfused rat kidney, whereas nonspecific pathways appear to play a major role in the renal folate reabsorption.

Analysis of Variance↗
PubMed1991

Antiarrhythmic drugs impair hepatic uptake and secretory function by different mechanisms in the isolated perfused rat liver.

In the present study the effect of various antiarrhythmic drugs on hepatic perfusion parameters, uptake capacity of organic anions and biliary secretion using the isolated perfused rat liver was examined. Infusion of verapamil (VP), diltiazem, N-propyl-ajmaline (NPAB), and quinidine at pharmacological doses induced consistently a 1.4-1.6-fold increase in portal pressure accompanied by a approximately 60% decrease in bile flow and a approximately 65% inhibition of biliary taurocholate (TC) excretion. Furthermore, hepatic uptake of oxygen, bromosulphthalein (BSP), and TC was significantly reduced. All these effects were dose-dependent and reversible upon withdrawal of the drugs. Studies of the hepatic circulation using a Trypan blue staining technique demonstrated a patchy perfusion pattern during infusion of the antiarrhythmic drugs as compared to the homogenously stained control organ. The hemodynamic alterations and the impairment of the hepatic initial uptake function could be entirely prevented by concomitant administration of the vasodilator papaverine. Bile flow and biliary TC excretion, however, were still inhibited under these conditions. The present results indicate that antiarrhythmic drugs produce cholestasis in the isolated perfused rat liver independently of their adverse effect on hepatic hemodynamics.

Animals↗