We compare the vasoreactive responses of Fluosol perfluorocarbon emulsion versus Earl's balanced salt+albumin solution as perfusates in an isolated perfused rat lung. Comparisons were made with three separate vasoconstrictive stimuli: norepinephrine, and prostaglandin F2 alpha dose-response analysis, and generation of hypoxic pulmonary vasoconstriction. The hypoxia experiments were also performed with ...

The relationship between the perfusion pressure (P) and resistance (R) of the intrahepatic portal vascular bed was determined in isolated rat liver preparations perfused with fresh, heparinized rat blood (hematocrit 30%), with rat blood containing a vasodilator agent (sodium nitroprusside, 1 X 10(-3) mol/L), or with 2.5% bovine serum albumin ...

We hypothesized that normotensive sepsis affects the ability of the microcirculation to appropriately regulate microregional red blood cell (RBC) flux. An extensor digitorum longus muscle preparation for intravital study was used to compare the distribution of RBC flux and the functional hyperemic response in SHAM rats and rats made septic ...

Extra-adrenal steroid 21-hydroxylation and 11 beta-hydroxylation occur in a variety of human tissues. This study was undertaken to determine whether the rat mesenteric artery produces corticosterone and to demonstrate the CYP11B1 mRNA in the vascular tissue. Isolated rat mesenteric arteries were perfused with Krebs-Ringer solution for 4 h. The perfusate ...

The aim of the investigation was to explore whether ursodeoxycholate, a tertiary bile acid with potential for treatment of chronic cholestasis in cirrhotic liver disease, has the same physiological effects in cirrhotic as in normal rats. Furthermore, we wanted to investigate whether ductular proliferation, as it occurred in this situation, ...

OBJECTIVE: The renal fractional clearance of [3H]DEAE dextran has been widely used to substantiate the charge selective model for renal permselectively, although there has only been one reported study on this type of clearance. This study sets out to examine the fractional clearance and glomerular processing of DEAE dextran. METHODS: ...

The binding of hepatic lipase to rat liver was studied in an ex vivo perfusion model. The livers were perfused with media containing partially purified rat hepatic lipase or bovine milk lipoprotein lipase. The activity of the enzymes was determined in the perfusion media before and after passage through the ...

BACKGROUND/AIMS: The cause of Reye's syndrome has not been completely defined. The rate of ketogenesis in the liver is a key determinant of, and reciprocally related to, triglyceride secretion. In the present study, 3-mercaptopropionic acid (MPA), a known inhibitor of mitochondrial long-chain acyl coenzyme A (CoA) dehydrogenase, was used to ...

Jejunal perfusion of cimetidine resulted in the appearance of lumenal cimetidine sulfoxide in both rats and humans. In the rat, ileal perfusion yielded negligible sulfoxide metabolite as compared with that of the jejunum. Jejunal co-perfusion of an anionic-exchange inhibitor, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, blocked the appearance of drug sulfoxide, and methionine co-perfusion ...

Pyrrolizidine alkaloids such as monocrotaline are bioactivated in the liver to pneumotoxins that cause pulmonary arterial hypertension and right ventricular hypertrophy. The release of the highly reactive, alkylating pyrrole, dehydromonocrotaline, from the isolated rat liver perfused with monocrotaline has now been demonstrated and quantified, using thiopropyl Sepharose resin as a ...

To clarify the stereoselective renal tubular secretion of an organic anion, renal excretion of 5-dimethylsulfamoyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carbox yli c acid (DBCA), a racemic compound, was studied with a single-pass perfused rat kidney preparation under constant perfusion pressure (ca. 120 mm Hg). The steady-state renal extraction ratio of (R)-(+)-DBCA (0.134) was 10 times ...

Microspectroscopy is used to investigate optical properties of haemoglobin-free perfused rat liver. Visible spectra of 20 microns diameter spot size were measured in transmission and/or reflection modes as a function of the thickness (< 1200 microns) of the liver-edge. Optical density (OD) in transmission mode increased with the increasing liver ...

Isolated liver with a recirculating perfusate was used to study 3'-azido-3'-deoxythymidine (AZT) disposition in phenobarbitone-pretreated rats at 68 microM AZT concentration in the reservoir. Clearance of AZT in the livers obtained from control animals was 0.42 +/- 0.01 (mean +/- s.d.) mL min-1/10 g liver. Over the study period of ...

We investigated in the isolated perfused rat liver (IPRL) whether product inhibition of metabolism contributes to the dose-dependent bioavailability of propranolol, a drug with a high, but saturable, hepatic first-pass effect. (+/-)-Propranolol was infused in the IPRL, using a recirculating design, for three 36-min periods (n = 9). Mean steady-state ...

We have investigated the effect of rat liver perfusion with adriamycin on mitochondrial activities. Although the perfusion treatment per se induces some decline of respiratory activities, adriamycin strongly potentiates this effect; moreover the coenzyme Q9 content of the mitochondrial membrane is significantly lowered by the antibiotic. Coaddition of coenzyme Q10 ...

Drug metabolism in the liver was examined by the rat isolated perfused liver using the single-pass bolus-input technique. The test compounds, allopurinol and its metabolite oxipurinol, were independently introduced into the liver from the portal vein, and the concentration profiles in the venous outflow were monitored and kinetically analysed by ...

The effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and stroma-free hemoglobin (SFH) on vascular responsiveness to various vasoactive substances were examined in isolated perfused rat kidneys. The kidneys isolated from rats were perfused with 6% PHP, 6% SFH, and 6% hydroxyethylstarch (HES) solution at a constant flow rate. Vascular responsiveness ...

The factors affecting drug elimination following acute administration of carbon tetrachloride (CCl4) were investigated using a perfused rat liver system. Morphine and pethidine were used as markers of hepatic glucuronidation and oxidation, respectively. Hepatoxicity of CCl4 was indicated by widespread cellular necrosis and raised serum asparatate aminotransferase levels. At a ...

The effect of reactive oxygen generation on intact livers was studied. Production of reactive oxygen species in perfused livers isolated from normal and endotoxin-treated rats was measured using chemically enhanced chemiluminescence. The resting state chemiluminescence of the livers increased on endotoxin administration and was maximal about 6 h after treatment. ...

Nifurtimox disposition was investigated using the rat isolated perfused-liver method after administration of 25 micrograms mL-1 nifurtimox, and its disappearance was monitored by analysing the perfusate sample at various times. Biliary excretion was also measured. The drug concentration profile underwent a biexponential decline over the 2-h study period, with a ...

Gluconeogenesis from lactate and pyruvate and associated parameters were investigated in the bivascularly and hemoglobin-free perfused rat liver. The substrates were infused either via the portal vein (anterograde perfusion mode), via the hepatic vein (retrograde mode) or via the hepatic artery (anterograde and retrograde modes). The rates of lactate and ...

Blockade of kappa-opioid receptors in the medial basal hypothalamus (MBH) with nor-binaltorphimine (nor-BNI) stimulates luteinizing hormone (LH) release during midpregnancy in the rat [48]. The objective of this study was to determine whether norepinephrine (NE) or dopamine (DA) mediates the LH response to blockade of MBH kappa-opioid receptors on days ...

Previous studies on Wistar-Furth rat intestinal mucosal capillaries show a variation in extent of binding of cationized ferritin (CF) to the endothelial surface. Three possible causes of this variation were investigated: 1) location of capillaries along the intestine, 2) time after feeding, and 3) effect of short-term hemostasis. In studies ...

The duodenal transfer and metabolism of [3H]tyramine from sacs and perfused segments of rat intestine were determined. In sacs, a linear relationship between the steady-state transfer rate of total tritium and the initial mucosal tyramine concentration was observed, suggesting that the clearance is the same at different concentrations. In duodenal ...

Interferons (IFN) inhibit activity of many isoenzymes of the hepatic microsomal cytochrome P-450 system. This inhibition is species specific. Lidocaine is metabolized by cytochrome P-450 III A 4. We investigated in the rat the effect of rat alpha-IFN on lidocaine elimination and on its extraction by the isolated perfused rat ...

Polymorphonuclear neutrophils (PMNs) have been implicated in microvascular injury following ischemia and reperfusion (I/R) but the relative contribution of obstruction versus toxic mediators is not well defined. Therefore, the present study was performed to determine the contribution of exogenous or endogenous activation on PMN-induced microvascular and hepatocyte injury. Rat livers ...

A within-subject dose-response analysis was conducted by locally perfusing increasing concentrations (0.1, 1, 10 and 100 microM) of the selective D2 agonist quinpirole via a microdialysis probe into the neostriatum of urethane-anesthetized rat pups 5, 10-11, 15-16 and 21-22 days of age and adult rats. In Expt. 1, K(+)-evoked dopamine ...

A protocol of constant infusion of fructose has been carried out both in human volunteers and in the perfused rat liver, aiming at a steady-state blood fructose concentration of 6-8 mM. Localized 31P-NMR spectroscopy and biochemical analyses were used to evaluate the metabolic changes. Comparison of the model experiment and ...

1. Protection against 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity by two nitric oxide-related compounds, N omega-nitro-L-arginine (L-NOARG) and L-arginine, was studied in the corpus striatum by means of two MPP+ perfusions separated by 24 h. Dopamine extracellular output after the second MPP+ (1, 5 and 10 mM) perfusion was considered as an ...

Degradation of atracurium by Hofmann elimination and ester hydrolysis depends mainly on pH and temperature and is said to be independent of liver and kidney function. Consequently atracurium is used widely in patients with liver failure. However, there is evidence that incubation of atracurium at 37 degrees C and pH ...

The interaction between P-glycoprotein modulators and P-glycoprotein mediated transport was investigated using rhodamine 123 in the isolated perfused rat liver of a mutant (TR-) rat strain. TR- rats, deficient in the canalicular multispecific anion transport system, are unable to extrude organic anions (glucuronides) and therefore excrete solely unconjugated rhodamine 123 ...

We examined conversion of Big endothelin-1 (ET-1) to mature ET-1 and pressor action during perfusion of the isolated perfused rat lung with Big ET-1. Big ET-1 caused a concentration-related increase in perfusion pressure and the pressor molar potency of the peptide was fivefold less than that of ET-1. Pressor responses ...

A series of 2'-(O-acyl) derivatives of 9-(2-hydroxyethoxymethyl)guanine (acyclovir) was synthesized by acid anhydride esterification. Aqueous solubilities in isotonic phosphate buffer (pH 7.4), partition coefficients in 1-octanol/phosphate buffer, and hydrolysis kinetics in rat plasma were determined. The ester prodrugs showed consistent increases in lipophilicity with corresponding decreases in aqueous solubility as ...

Semicarbazide-sensitive amine oxidase (SSAO) activity in rat vascular smooth muscle cells is associated extensively with the plasmalemma. To determine which side of the plasmalemma the active sites of these enzymes face, the non-permeating agent, diazotised sulphanilic acid (DSA; 4.4 mM) was perfused through the isolated mesenteric arterial bed of the ...

We performed this study to examine the presence of a kallikrein-kinin system in rat fetal and maternal tissues. Uteri and placenta from Wistar pregnant and nonpregnant rats were perfused to eliminate blood, and fetal membranes were washed several times with saline. Amniotic fluids were obtained without blood contamination by amniocentesis ...

Microdialysis was used to estimate in vivo tyrosine hydroxylase (TH) activity in locus coeruleus (LC) of conscious rats. An aromatic amino acid decarboxylase inhibitor, difluoromethyl-DOPA (DFMD), was perfused through the dialysis probe and the DOPA accumulating in dialysates was measured. A 3 h perfusion of a 6 x 10(-4) mol/l ...

The pharmacokinetics and metabolism of radiolabelled salicylate were studied in rats and compared with that of the isolated perfused rat liver and the perfused rat kidney. Both parent compound and salicylate metabolites (mainly conjugates with glycine and glucuronic acid) were eliminated mostly into urine. The comparison of a relative proportion ...

Intracellular pH (pHi) has been measured in intact, perfused rat mandibular salivary glands loaded with the fluorescent pH indicator BCECF [2',7'-bis(2-carboxyethyl)-5(6)- carboxyfluorescein]. Glands mounted in the cuvette of a conventional bench-top spectro-fluorometer were perfused for 5 min with the acetoxymethyl ester of BCECF and fluorescence was measured ratiometrically at 6-s ...

The system of perfusing rat livers has been used to evaluate the uptake and incorporation of liposomal CoQ10 into mitochondria. After 90 minutes of perfusion the cells are strongly enriched in CoQ10 up to levels of the same order of magnitude as CoQ9. Heavy and light mitochondrial crude subcellular fractions, ...

We dissected and perfused outer medullary vasa recta (OMVR) from vascular bundles in the rat. Permeabilities of sodium (PNa) and urea (Pu) were simultaneously determined from the lumen-to-bath efflux of 22Na and [14C]urea. PNa and Pu were also measured by in vivo microperfusion of descending (DVR) and ascending vasa recta ...

Endothelin-1 or sarafotoxin 6c (10(-12) to 10(-9) M) induced concentration-dependent increases in perfusion pressure in the isolated perfused kidney of the rat, and increased the release of 6-keto-prostaglandin F1 alpha, prostaglandin E2 and prostaglandin F2 alpha. The pressor effects of endothelin-1 were partially antagonised by BQ-123 (10(-6) M) and more ...

After i.v. injection of 833 x 10(3) microfilariae (mf) per animal (150 g) into naive recipient cotton rats, at autopsy 15 min thereafter 30.4% of them could be recovered as a total: 19.1% were proved in the peripheral circulating blood (PCB) completely intact. 6.5% were recovered by perfusion of the ...

At least three independent groups of natriuretic hormones have been isolated over the past ten years. Two, atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), are proteins and the third is made up of digitalis-like substances (DLS). The present report concerns the isolation, substantial purification and biologic actions of ...

Radiolabeled bioactive peptides may show receptor-mediated binding to tumors, making them suitable for scintigraphic imaging. The liver is an important organ for peptide clearance. To gain insight into the uptake and intracellular processing of somatostatin analogs, we compared the hepatobiliary handling of 125I-Tyr3-octreotide and 111In-DTPA-D-Phe1-octreotide, which are successfully used to ...

The influence of colchicine-specific Fab fragments on hepatic metabolism and biliary excretion of colchicine was studied in the isolated perfused rat liver. Isolated rat livers were perfused for 180 min with either [3H]colchicine (initial concentration: 50 ng/ml) or Fab-[3H] colchicine in a stoichiometrical proportion at a constant flow of 100 ...

Bile lipids are secreted in association with a newly identified major apoprotein called anionic polypeptide fraction-calcium binding protein (APF-CBP), which is synthesized in the hepatocytes and has been detected in both bile and plasma and characterized. The secretion of the lipids in bile depends both on the concentration and the ...

Cyclosporine has been used with increased frequency, occasionally in conjunction with cimetidine and omeprazole. The present study was undertaken to study a possible interaction between either of the two drugs and cyclosporine in the liver. The isolated perfused rat liver was used with recirculation of perfusate for 150 min. 6 ...

Intraneuronal and extracellular dopamine (DA) metabolism in rat striatum during inhibition of neurotransmission processes by tetrodotoxin (TTX) perfusion was examined by analysis of the striatal DA content and the amount of initial post-mortem DA output. In spite of there being an excess amount of DA already present in the striatum, ...

Antibodies against a synthetic peptide representing the 14 C-terminal amino acids of the N-terminal propeptide of rat and bovine procollagen type III were raised in rabbits and used to develop a radioimmunoassay. N-Terminal propeptide of procollagen type III, purified from calf skin, served as standard and tracer material. The IC50 ...

The effect of nutritional status on livers preserved either by simple cold storage or by hypothermic perfusion was studied using isolated rat liver perfusion model. Livers either form fed or fasted rats were preserved for 18 hours by simple cold storage procedure with UW solution, or continuously perfused for 12 ...