Isolated segments of rat cortical (cTAL) and medullary (mTAL) thick ascending limbs were microperfused and the transepithelial net fluxes (JX) were determined by measuring the composition of the collected fluid with an electron microprobe. When perfused with symmetrical solutions both segments showed similar JNa and JCl and lumen-positive transepithelial voltage ...

Bleeding from esophageal varices is highly lethal in cirrhotics, the main cause of death being liver failure. Because adequate hepatic perfusion is a prerequest for the maintenance of liver function, the present study was designed to evaluate the influence of hemorrhagic shock on liver microcirculation in rats with portal hypertension ...

Dogs were used as a large animal model to assess the feasibility and safety of a surgical method for gene transfer into hepatocytes in vivo. This method, which we previously described in rats, consists of a partial hepatectomy aimed at inducing liver regeneration, followed by the selective in situ perfusion ...

Glomeruli isolated from rats with bilateral ureteral obstruction (BUO) of 24 hr duration produced significantly greater amounts of prostaglandin (PG) E2, 6-keto-PGF1 alpha, thromboxane B2, and leukotriene B4 than glomeruli isolated from sham-operated control (SOC) rats. To examine the mechanisms underlying the greater production of eicosanoids by glomeruli isolated from ...

The technique of microdialysis was employed to investigate in vivo 5-hydroxytryptamine (5-HT) release in isolation-reared rats compared with socially reared rats. Two methods were employed to stimulate 5-HT release: local KCI injection into the frontal cortex of chloral hydrate anaesthetized rats, and the exposure of freely moving rats to a ...

The isolated liver perfusion technique was used to study the effect of therapeutic doses of paracetamol on hepatic gluconeogenesis and bromosulphthalein clearance from the perfusate and biliary excretion of the dye in the rat. Six groups of rats were studied; those in the three experimental groups were given 0.02 g ...

Using a new cannulation method, which completely prevented interruption of circulation to brain tissue during surgical operations, we could prepare a functionally intact hemoglobin-free isolated perfused rat head in situ. The frequency distribution (8-25 Hz) and amplitude of a spontaneous electroencephalogram, EEG (50 microV), were kept within the normal ranges ...

The metabolism of cysteine and related compounds was investigated in the isolated perfused hindquarter of the rat. An erythrocyte-based perfusion medium was used; use of a perfluorochemical emulsion, FC-43, resulted in apparent chemical oxidation of cysteine, whereas bovine erythrocytes did not appear to contribute significantly to the metabolism of cysteine. ...

In order to investigate the effect of fructose on the metabolic rates of liver glycolysis, changes in fructose 2,6-bisphosphate content and fructose 6-phosphate, 2-kinase (F6P2kinase) activity were examined using perfused rat liver. When the starved liver was perfused with 0.5 mM fructose, the fructose 2,6-bisphosphate level was 6.66 nmol/g liver, ...

To clarify the interaction between endothelin-1 (ET-1) and atrial natriuretic peptide (ANP), the effects of ET-1 on ANP secretion were investigated in isolated perfused rat hearts and in conscious unrestrained rats. Perfusion with 10(-9) M ET-1 stimulated ANP secretion from the isolated perfused rat heart. However, 10(-10) M ET-1 significantly ...

The effect of uremia on hepatic metabolism of aldosterone was studied in the isolated perfused liver of female Wistar rats. Uremia was induced by five-sixths partial nephrectomy 4 weeks before experiments. Isolated livers of normal and uremic rats were perfused at a constant flow rate with a hemoglobin-free medium, to ...

OBJECTIVE: Our aim was to test the hypothesis that maternofetal placental calcium transfer rate decreases in experimentally induced acute maternal hypermagnesemia in the rat. STUDY DESIGN: We measured the unidirectional maternofetal clearance of calcium 45 and chromium 51-ethylenediaminetetraacetic acid across in situ perfused placentas of rats randomized to intravenous treatment ...

Dimethylacetamide (DMAc) is a skin-penetrating solvent able to induce hepatic damage after chronic exposure. Previous research has indicated that metabolism may be saturated at its present TLV/TWA (10 ppm). Biological monitoring of monomethylacetamide (MMAc), the primary metabolite of DMAc, might therefore underestimate exposure to DMAc and related health hazards. We ...

Radiolabeled Borrelia burgdorferi, the etiologic agent of Lyme disease, injected intravenously into rats are cleared from the vasculature within 1 h of injection. One low passage isolate showed trafficking between the circulation and possibly the vessel walls for the first 2 h after injection. All strains used were resistant to ...

In the isolated perfused rat mesenteric vasculature with intestine attached N omega-nitro-L-arginine (L-NNA) (30 mumol/l), an inhibitor of nitric oxide (NO) synthesis from L-arginine, did not alter spontaneous noradrenaline outflow. Transmural field stimulation (2-10 Hz) caused a frequency-dependent increase in noradrenaline outflow. The evoked overflow was reduced by L-NNA. L-Arginine ...

Insulin response to glucose is severely impaired in patients with non-insulin-dependent diabetes mellitus (NIDDM). Also in a rat model of NIDDM, neonatally streptozotocin diabetic rats (STZ), the insulin response to glucose is profoundly suppressed when studied in vivo or in the perfused pancreas. The insulin response was better preserved from ...

The source and function of elevated uracil release during vasoconstriction in the perfused rat hindlimb was investigated. The possibility that uracil release derived from the breakdown of released vasoactive uridine 5'-triphosphate (UTP) was examined. Exogenous UTP was found to be a potent vasodilator in the perfused rat hindlimb, opposing norepinephrine ...

RATIONALE AND OBJECTIVES: Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a recently introduced experimental magnetic resonance (MR) contrast agent for hepatic imaging. Although liver enhancement has been investigated in a number of animal models, tolerance evaluations of Gd-EOB-DTPA injection have been limited. METHODS: The authors investigated acute hepatotoxicity in an isolated perfused rat liver ...

We have accumulated evidence that coenzyme Q (CoQ) concentration in the mitochondrial membrane is not saturating for NADH oxidation but is saturating for succinate and glycerol-3-phosphate oxidation. As a result of its kinetic properties CoQ concentration changes must yield changes in respiration rates. This provides a rationale for the reported ...

Using a bivascularly perfused rat liver, we investigated the hepatic extraction and hepatic action on glucose output of insulin, glucagon, and epinephrine. The liver was perfused for 70 min without recirculation via the portal vein and hepatic artery (3.0 ml/(min.g liver) from portal vein and 1.0 ml/(min.g liver) from celiac ...

The effect of atropine on gastrointestinal motility and the bioavailability of cyclosporine A (CyA) was studied in rats. Atropine dose-dependently inhibited gastrointestinal motility, and the ID20 and ID50 doses of atropine were chosen to study the bioavailability of CyA. After oral administration of CyA, the bioavailability was about 27%, and ...

The effect of buformin, a biguanide, on gluconeogenesis from 10 mM alanine in the presence of 143 nM glucagon were studied using isolated rat liver perfusions. In addition, to investigate possible mechanisms of biguanide action, alanine utilization in isolated rat liver perfusion and [3H]alanine uptake in isolated hepatocytes were observed. ...

The application of the axial dispersion model to diazepam hepatic elimination was evaluated using data obtained for impulse-response experiments with diazepam in the single-pass isolated perfused rat liver preparation. The transient form of the two-compartment dispersion model was applied to the output concentration versus time profile of diazepam after bolus ...

1. Ethacrynic acid (EA), a phenoxyacetic acid diuretic, has similar effects to tienilic acid (TA) on rat liver glutathione S-transferase (GST) activity in vitro, using either 1-chloro-2,4-dinitrobenzene or sulphobromophthalein (BSP) as a substrate. EA inhibits the basic rat liver GST, with inhibition being greater with GST containing subunits 3 and ...

We have attempted to direct low molecular weight compounds to the liver via the internalizing asialoglycoprotein receptor on parenchymal cells by conjugation to a monomeric triantennary galactosyl cluster. Acetate and a hypolipidaemic ansamycin were derivatized and the biodistribution of the conjugates was determined 250 sec and 30 min after administration ...

A sizeable pre-epithelial diffusion barrier (unstirred layer) is present during perfusion of the rat jejunum. In the present study, three rapidly transported compounds, CO, [14C]warfarin, and glucose (5.5 mmol/L), were used as probes to assess the ability of manipulations to reduce the unstirred layer. This layer was 700-800 microns thick ...

We have examined the relationship between the metabolism of the pyrrolizidine alkaloid, monocrotaline, and glutathione concentration in the isolated, perfused rat liver. On perfusion of monocrotaline (300 microM) through the isolated liver, high concentrations (1.1 mM) of its metabolite glutathionyldehydroretronecine are released into bile, while much lower amounts (4.86 microM; ...

The single oligosaccharide attachment in rat transferrin exhibits marked structural microheterogeneity. In this study we examined whether all microheterogeneous forms of rat transferrin found in plasma are derived from a single organ, such as the liver. To this end we analyzed the glycans of rat transferrin synthesized by the isolated ...

The rate and extent of hepatic distribution of antipyrine was examined in the rat isolated perfused liver. Tritiated water and [14C]antipyrine were injected simultaneously into the portal vein as a bolus using either Krebs-Ringer bicarbonate or rat plasma as the perfusate. The effluent profiles of each compound using the two ...

The purpose of this study was to test the hypothesis that different hepatocellular functions are regulated individually during sepsis. This was done by simultaneously measuring bile production, release of liver transaminases, and synthesis of secreted proteins in perfused livers from control and septic rats. Sepsis was induced by cecal ligation ...

Intrinsic liver function may be specifically studied using the isolated perfused liver system. In this report, the metabolic characteristics of the perfused rat liver are described in response to lactate (5 mM) and ammonia (10 mM) loading. These conditions are analogous to the increased substrate availability that accompanies some acute ...

The pharmacokinetics of atracurium, which is degraded by Hofmann decomposition and ester hydrolysis, is not altered by impaired liver function. Atracurium should, therefore, be ideal for patients with heptic failure, and is now widely used in clinical practice. However, some studies reported considerable hepatotoxicity after atracurium, especially from its breakdown ...

The 31P NMR visibility of ATP of the perfused rat liver was tested over a wide range of metabolic conditions, including normoxic and hypoxic perfusions, fructose loads, and various intervals of normothermic ischemia, for both ad libitum fed and 24-h fasted rats. The 31P NMR signal of ATP was compared ...

The antipyretic effect of arginine vasopressin (AVP) introduced into the ventral septal area (VSA) by push-pull perfusion was investigated in the urethane-anaesthetized rat. In addition, experiments were carried out to determine whether AVP could suppress fever when similarly perfused within the medial amygdaloid nucleus (meA). During push-pull perfusion of artificial ...

We have modified the apparatus for isolated rat liver perfusion (IPRL) in order to be able to perform two perfusions simultaneously. In addition, we studied the quality and stability of livers by comparison of five different perfusates: Blood (Group A), Original Krebs Henseleit buffer (Group B), Krebs buffer with glucose ...

The effects of low-density lipoprotein (LDL) on cyclosporine (CyA) metabolism were studied in the isolated perfused rat liver, in a recirculating mode, using Krebs-Ringer buffer in the absence (control perfusion) or presence of LDL (1 microM) (LDL perfusion). In the LDL perfusions, CyA concentrations at all sampling times were about ...

The effects were studied of improved oxygen supply on the integrity and metabolic activity towards dimethylacetamide of the isolated perfused rat liver. Improvement of oxygen supply by increased medium oxygenation or addition of chemical oxygen carriers (perfluortributylamine) or erythrocytes led to increased bile secretion. Leakage of lactate dehydrogenase and aspartate ...

Transcapillary CO2 exchange entails a transient perfusate CO2-HCO3(-)-H+ disequilibrium, leading to net loading or unloading of blood HCO3-. Perfusate reequilibration may or may not reach completion during the time of capillary transit, depending on the rate of intracapillary CO2-HCO3(-)-H+ reactions. Failure to reestablish equilibrium within the "open" capillary system leads ...

Effects of sensitizing antigen (ovalbumin) on various physiological and hepatic parameters were investigated in sensitized rats and isolated perfused livers derived from sensitized rats. Administration of ovalbumin (500 micrograms) to the portal venous circulation of sensitized but not nonsensitized rats resulted in a rapid and sustained decrease in systemic arterial ...

S-8666 (5-dimethyl-sulfamoyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxylic acid), a novel uricosuric antihypertensive diuretic, and its N-monodemethylated metabolite (M-I) were studied in a single pass perfused rat liver preparation under constant perfusate flow (ca. 16 ml/min). During perfusion with 100 nmol/ml of racemic S-8666 not containing bovine serum albumin (BSA), the steady-state hepatic extraction ratio of ...

Debrisoquin undergoes oxidative metabolism to 4-hydroxydebrisoquin, catalyzed by cytochrome CYP2D1 in rats and CYP2D6 in humans. Cytochrome CYP2D6 also plays a major role in dextromethorphan O-demethylation. In preliminary studies in perfused Lewis rat livers, we observed a difference in repeat clearance experiments using debrisoquin, but not dextromethorphan. To determine whether ...

In order to investigate the regulatory mechanism for the atrial release of atrial natriuretic peptide (ANP), a perfused rabbit atrial model was devised. In the present experiments, the effect of a reduction in atrial distension on the immunoreactive ANP (irANP) secretion was investigated and compared in the perfused right and ...

De novo synthesis and excretion into perfusate and bile fluid of hepatic gangliosides were studied in isolated perfused rat livers. Addition of N-acetyl-[6-3H(n)]D-mannosamine to the perfusate resulted in radioactive synthesis of at least eight gangliosides labeled in their sialic acid residues. About 10% of total de novo synthesized gangliosides were ...

We examined the influence of nutritional state on the role of the hepatic plasma membrane lactate transporter in determining overall hepatic lactate disposal. The effects of infusion of sodium D-3-hydroxybutyrate (DOHB) on lactate uptake were studied in perfused livers from fed or starved rats. In livers from starved rats, DOHB ...

We describe a simple method of performing sequential excision biopsies during liver reperfusion in the isolated perfused rat liver. After hepatectomy, four ligatures (5.0 silk) tied with a slip knot are placed around the pedicles of: (1) the inferior and (2) the superior parts of the caudate lobe, as well ...

We examine here the delivery of gangliosides from the perfused rat liver into the perfusate. One hour after the administration of [3H]GM1 to recirculating perfused livers, almost 80% of the perfusate radioactive gangliosides were recovered associated to the HDL fraction. This fraction was relatively enriched in radioactive GD1a. The pattern ...

1. The regulation of the splenic perfusion during normal and pathological conditions is incompletely understood. We studied the time course of splenic blood flow during the initial (0-24 h) development of haemorrhagic anaemia in awake and anaesthetized rats, as well as in awake rabbits and cats. Another group of rats ...

A new approach in the treatment of gastrointestinal tumors with 5-fluorouracil involves the infusion of high doses of uridine to improve the chemotherapeutic efficiency of the former. High amounts of uracil formed from uridine can interfere with the hepatic catabolism of 5-fluorouracil and thus increase its bioavailability and toxicity. In ...

Perfused rat liver can be considered as one of the most suitable ex vivo models for studies of liver metabolism. To assess the possible effect of L-carnitine and some of its acyl esters on proteolysis in the rat liver, the amino acid derivatization and high-performance liquid chromatographic separation of Tapuhi ...

The clearance in vivo of rat C-reactive protein (CRP) was studied: (i) in the whole animal and (ii) by using a rat liver perfusion system. Rat CRP is a glycosylated serum protein containing a complex-type biantennary carbohydrate structure on each of its five subunits. The half-life of rat asialo CRP ...