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.

SourceResearch connectionFrom yearThrough year

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

At least 181 records · Page 10Linked to original sources

PubMed1980

Effect of phosphate on the arginine-induced insulin release by the isolated perfused rat pancreas.

The isolated perfused rat pancreas was used to investigate the effect of extracellular phosphate on the arginine-induced insulin release. In the absence of any metabolic substrate, the insulin response to arginine was monophasic. In the absence of phosphate in the medium, the insulin release as unaffected until the 15th minute of the stimulation period, but was significantly augmented from that time onward. In the presence of oleic acid in the perfusate, the insulin response to arginine was also monophasic but occurred earlier than in controls. In this conditin, phosphate omission resulted in an increase of the insulin response to arginine from the 3rd minute of the stimulatory period onward. In the presence of glucose 5.5 mM in the medium the insulin response to argnine was biphasic and was not affected by extracellular phosphate omission.

Animals↗

PubMed1995

Disposition of quinapril and quinaprilat in the isolated perfused rat kidney.

An isolated perfused rat kidney model was used to probe the renal disposition of quinapril and quinaprilat after separate administration of each drug species. Control studies were performed with drug-free perfusate (n = 8) and perfusate containing quinapril (n = 9) or quinaprilat (n = 7) at initial drug concentrations of 1000 ng/ml (including corresponding tracer levels of tritiated drug). Physiologic parameters were within the normal range of values for this technique and were stable for the duration of each experiment. Quinapril and quinaprilat concentrations were determined in perfusate, urine, and perfusate ultrafiltrate using a specific and sensitive reversed-phase HPLC procedure with radiochemical detection, coupled to liquid scintillation spectrometry. Perfusate protein binding was determined using an ultrafiltration method at 37 degrees C. The total renal clearance of quinapril (CLr) was calculated as Dose/AUC(0-infinity), and is represented by the sum of its urinary and metabolic clearances. The urinary clearances (CLe) of quinapril and quinaprilat were calculated as urinary excretion rate divided by midpoint perfusate concentration for each respective species. Of the total renal clearance for quinapril (CLr = 4.49 ml/min), less than 0.1% was cleared as unchanged drug (CLe = 0.004 ml/min); over 99% of the drug was cleared as quinaprilat formed in the kidney. The clearance ratio of quinapril [CR = CLr/(fu.GFR)] was 41.0, a value representing extensive tubular secretion into the renal cells. Following quinaprilat administration, the clearance ratio of metabolite [CR = CLe/(fu.GFR)] was 3.85, indicating a net secretion process for renal elimination.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1989

Splanchnic neural regulation of pancreatic polypeptide release in the isolated perfused human pancreas.

The isolated perfused human pancreas was employed as a model in which electrical stimulation of the celiac mixed neural bundle was performed in the presence and absence of selective neural antagonists. Stimulation of the celiac neural bundle in the presence of hyperglycemia resulted in augmentation of pancreatic polypeptide release. Cholinergic stimulation appears to predominate, whereas beta-adrenergic fibers stimulate pancreatic polypeptide-cell secretion, and alpha-adrenergic fibers inhibit pancreatic polypeptide release. During euglycemia, both cholinergic stimulation and gastric inhibitory polypeptide infusion resulted in a marked release of pancreatic polypeptide. These stimulatory effects were additive, which suggests a linked hormonal and neural mechanism of pancreatic polypeptide release after a meal. In this in vitro human model, our data confirm that the splanchnic innervation of the pancreas has a potent regulatory role in pancreatic hormone release in man.

Adolescent↗

PubMed1985

Regulation of canalicular bile formation by alpha-adrenergic action and by external ATP in the isolated perfused rat liver.

In isolated perfused rat liver, addition of adrenaline induced a complex response of bile flow including rapid, reversible stimulation (1/2-2 min), reversible inhibition (2-10 min), and prolonged stimulation. Both the reversible stimulation and the inhibition were mimicked by the alpha-sympathomimetic agonist phenylephrine but not by the beta-agonist isoproterenol. The reversible stimulation was a very early effect being terminated prior to all other alpha-adrenergic responses of liver. External ATP considerably lowered bile flow while inducing release of glucose and lactate, inhibition of respiration, and a reversible efflux of Ca2+. Variations of mannitol clearance parallel to those of bile flow indicate a canalicular origin of all changes.

Adenosine Triphosphate↗

PubMed1988

Synergistic effects of hypoxia and fasting on harmol elimination in the isolated perfused rat liver.

In isolated hepatocytes the availability of intracellular glucose appears to be a key factor controlling the rate of xenobiotic glucuronidation during hypoxia. This study in the isolated perfused rat liver examines the effect of both a 24-hr fast and removal of glucose (8 mM) from liver perfusate on the elimination of bolus doses of harmol (20 mumol) under normoxic and hypoxic conditions. In the preparations used in these experiments, harmol glucuronide is the major metabolite (greater than 80%) with the remainder being sulphate. During normal oxygenation, in the livers from fed rats, harmol was rapidly eliminated (t1/2 = 4.2 +/- 0.4 min; mean +/- SD, N = 4). Fasting led to a small reduction in harmol elimination rate (t1/2 = 5.6 +/- 0.4 min; P less than 0.025) while removal of glucose from perfusate made no difference in either fed or fasted preparations. In the same livers, a second bolus dose of harmol was given during hypoxia. This produced a modest decline in harmol elimination in fed rats (t1/2 = 7.1 +/- 2.0 min; P less than 0.05). However, in fasted rats there was a striking reduction in harmol elimination (t1/2 = 109.8 +/- 54.0 min; P less than 0.025). The removal of glucose from perfusate made no significant difference to these results (t1/2 = 253 +/- 209 min in fasted preparations, P greater than 0.1). In all preparations, reoxygenation resulted in a rapid recovery of drug elimination. We conclude that nutritional state is important in determining the impact of hypoxia on harmol elimination by the liver. This study suggests that clinically significant reductions in xenobiotic glucuronidation are most likely to occur in poorly nourished or fasted subjects who became hypoxaemic.

Alkaloids↗

PubMed1977

Cortisol metabolism and excretion in the isolated perfused rat kidney.

The isolated perfused rat kidney allows a simultaneous kinetic study of both the renal metabolism and the urinary excretion of cortisol and its metabolites in the rat. In this system, cortisol was completely metabolized within 120 minutes. The main renal metabolites of cortisol (cortisone, 20 reduced cortisol and 20 reduced cortisone) were found in the recirculating perfusate and in urine. The formation of these metabolites was quantitatively evaluated and compared to a theoretical model.

Animals↗

PubMed1992

Nervous control of the release of substance P and neurokinin A from the isolated perfused porcine ileum.

Using isolated perfused porcine ileum we studied the release of substance P (SP) and neurokinin A (NKA) in response to electrical stimulation of the mixed periarterial nerves and to infusion of different neuroactive agents. Nerve stimulation (8 Hz) had no significant effect on the release of SP and NKA. Nerve stimulation also had no effect on the release of SP and NKA during infusion of atropine (10(-6) M) or phentolamine (10(-5) M), whereas a significant increase (from 8.2 +/- 1.9 to 20.1 +/- 4.6 pmol/l for SP and from 12.3 +/- 2.7 to 34.2 +/- 7.7 pmol/l for NKA, n = 7) was observed during nerve stimulation after pretreatment with both atropine and phentolamine. This increase was abolished by hexamethonium (3 x 10(-5) M). Also acetylcholine infusion causes a significant release of SP and NKA after infusion of both atropine and phentolamine (to 172 +/- 56% and 232 +/- 69% of basal release, n = 7), an effect that was abolished by hexamethonium infusion. Infusion of atropine alone increased the release of SP and NKA significantly (to 337 +/- 92% and 386 +/- 124% of basal output, n = 5). Norepinephrine (10(-6) M) inhibited the release of SP and NKA (to 69 +/- 6% and 80 +/- 6% of basal release, n = 7). Our results suggest that the SP- and NKA-producing neurons receive intrinsic tonic muscarinic inhibitory impulses, extrinsic nicotinic excitatory impulses, and extrinsic adrenergic inhibitory impulses.

Acetylcholine↗

PubMed1985

Effect of gastrointestinal hormones on choleresis from the isolated perfused rat liver.

Using isolated perfused rat liver, the direct effect of secretin, glucagon, caerulein, insulin and somatostatin on choleresis was investigated. When the liver was perfused in the absence of sodium taurocholate, the bile volumes were: control, 0.33 +/- 0.01 (mean +/- S.E.M.) ml/10 g liver per 50 min; secretin 0.05 U/ml, 0.39 +/- 0.01 (P less than 0.01); glucagon 10(-10) M, 0.44 +/- 0.02 (P less than 0.01); caerulein 10(-8) M, 0.34 +/- 0.03 (n.s.); insulin 1 mU/ml, 0.35 +/- 0.02 (n.s.); glucagon plus somatostatin 10(-7) M, 0.46 +/- 0.03 (n.s. vs. glucagon alone), respectively. When 10(-5) M sodium taurocholate was present in the perfusate, the bile volumes were: control, 0.61 +/- 0.03; secretin, 0.63 +/- 0.01 (n.s.); glucagon, 0.70 +/- 0.01 (P less than 0.05); caerulein, 0.55 +/- 0.01 (n.s.); insulin, 0.62 +/- 0.04 (n.s.); somatostatin, 0.59 +/- 0.01 (n.s.); respectively. Glucagon increased glucose output and cyclic AMP in the effluent from the liver neither of which were suppressed by somatostatin. Secretin increased cyclic AMP but not glucose output. These results indicate that glucagon has the most potent action on bile acid-independent canalicular bile, that caerulein and insulin do not act on canalicular bile production directly and that somatostatin does not directly suppress canalicular bile production nor hepatic glucose output produced by glucagon in rats.

Animals↗

PubMed1990

Biological properties of the 2-fluoro-beta-alanine conjugates of cholic acid and chenodeoxycholic acid in the isolated perfused rat liver.

The isolated perfused rat liver was used to examine the hepatic extraction, biliary secretion and effect on bile flow of the 2-fluoro-beta-alanine conjugates of cholic acid and chenodeoxycholic acid. The naturally occurring taurine and glycine conjugates of these bile acids were used for comparisons. The 2-fluoro-beta-alanine conjugates were extracted by the liver to a similar extent as the taurine and glycine conjugates. The biliary secretion rate and increase in bile flow were similar for all the cholic acid conjugates. On the other hand, the maximal biliary secretion rate of the 2-fluoro-beta-alanine conjugate of chenodeoxycholate was similar to that of the glycochenodeoxycholate, but 47% lower than that of taurochenodeoxycholate. In addition, the 2-fluoro-beta-alanine conjugate of chenodeoxycholate produced a decrease in bile flow that was comparable to that observed with the glycochenodeoxycholate (54% vs. 74%), but which was greater than that produced by the taurochenodeoxycholate (12%). In summary, these data demonstrate that the biological properties of the 2-fluoro-beta-alanine conjugates of cholic acid and chenodeoxycholic acid are not markedly different from those of the naturally occurring taurine and glycine conjugates. These data also suggest that the amino acid moiety can influence the biliary secretion and cholestatic properties of chenodeoxycholic acid conjugates.

Alanine↗

PubMed1965

THE INCORPORATION OF CARBON DIOXIDE INTO MILK CITRATE IN THE ISOLATED PERFUSED GOAT UDDER.

1. Isolated perfused goat udders supplied with glucose, acetate and amino acids were infused for several hours with NaH(14)CO(3). 2. Lactose, milk-fat fatty acids and glycerol had very little radioactivity. The specific radioactivity (counts./min./mg. of C) of milk citrate was 9-16% that of the carbon dioxide in the perfusion fluid and 19% that estimated for tissue carbon dioxide. The specific radioactivity of tissue citrate resembled that of milk citrate. 3. The radioactivity in citrate was predominantly in C-6, suggesting some carboxylation of alpha-oxoglutarate in addition to carboxylation of C(3) compounds. 4. [1-(14)C]Glutamate was infused in a similar experiment, and milk citrate radioactivity was predominantly in C-1+C-5. 5. The results are discussed in relation to the contribution of glucose and acetate carbon to citrate. The implications of the carboxylation of alpha-oxoglutarate are considered.

Acetates↗

PubMed1980

The renal clearance of thyroid hormones in the isolated perfused rat kidney.

The isolated perfused rat kidney was used to study renal handling of thyroid hormones. Substrate enriched protein free perfusates were chosen which allowed the kidneys to perform a normal glomerular filtration rate of 1.1 ml/g kidney x min and enabled accurate estimation of filtered load and tubular handling of free thyroid hormones without interference from the presence of hormone binding substances. Under these conditions we found a high tubular reabsorption capacity for both T3 and T4. This reabsorption capacity was unsaturable, even when the filtered hormone load was far above (x 100) the physiological range.

Absorption↗

PubMedDate not supplied

Effect of endothelial damage on prostaglandin synthesis by isolated perfused rabbit mesenteric vasculature.

Isolated perfused rabbit mesenteric blood vessels selectively metabolized arachidonic acid to prostacyclin (prostaglandin I2). However, the less lipid soluble prostaglandin endoperoxide (PGH2) administered exogenously was not metabolized by vascular prostacyclin synthetase but was partially degraded to prostaglandin E2 (PGE2). Peptide stimulation (e.g., angiotensin II, bradykinin) resulted in formation of both PGI2 and PGE2 from endogenous arachidonic acid. Denuding the blood vessels of their endothelial layer by perfusion with hypotonic fluid did not affect the metabolism of arachidonic acid or the response to peptide stimulation, suggesting that the cyclooxygenase, prostacyclin synthetase, and angiotensin II receptors are present and functional in the subendothelial smooth muscle cells of the vessel walls. In contrast, exogenous PGH2 either escaped completely unmetabolized or was converted to both PGI2 and PGE2 in the presence of vascular injury induced by hypotonic fluid.

Angiotensin II↗

PubMed1981

Regulation of plasma ferritin by the isolated perfused rat liver.

The isolated perfused rat liver has been used to investigate the regulation of plasma ferritin in normal, iron-deficient and iron-overloaded states. Both 125I-labelled and non-labelled rat liver ferritins were rapidly cleared from the perfusion circuit with a half-life of approximately 30 min. Perfusion of livers from normal, iron-loaded or iron-deficient rats with blood obtained from normal, iron-loaded or iron-deficient rats showed that the liver takes up plasma ferritin, and releases ferritin into the perfusate to achieve a perfusate ferritin level appropriate to the iron stores of the animal from which the liver was taken. It is concluded that the liver is capable of both uptake and release of ferritin and that within the liver there resides a mechanism which maintains circulating ferritin concentrations at a level appropriate to body iron stores.

Animals↗

PubMed1984

Regulation of hepatic glutamate metabolism. Role of 2-oxoacids in glutamate release from isolated perfused rat liver.

In isolated perfused rat liver, addition of the oxoanalogues of leucine, isoleucine, methionine and phenylalanine is followed by a rapid and reversible stimulation of glutamate release. This is not observed with the corresponding amino acids or 2-oxoisovalerate, 2-oxoglutarate or oxaloacetate. The increased glutamate release by the liver is accompanied by a decrease in the tissue contents of 2-oxoglutarate and glutamate by about 25% and 50%, respectively. During the metabolism of glutamine, i.e. conditions with elevated tissue glutamate concentrations, 2-oxoacid-induced glutamate release is stimulated. In the presence of glutamine (5 mM), 2-oxoisocaproate, 2-oxo-4-methylvalerate and 2-oxo-4-methylthiobutyrate were found to be most effective and glutamate release by the liver increased linearly from about 80 nmol g-1 min-1 to 600 nmol g-1 min-1 at increasing 2-oxoacid concentrations up to 1 mM. When glutamate tissue levels were decreased by phenylephrine, stimulation of glutamate release by 2-oxoisocaproate was markedly diminished. 2-Oxoacid-stimulated glutamate release is independent of oxoacid metabolism, indicating that the effect is probably not explained by a 2-oxoacid/glutamate exchange across the liver plasma membrane. 2-Oxoacid-induced glutamate export predominantly occurs in a sodium-independent way. At low concentrations of 2-oxoisocaproate (below 0.2 mM), the increased glutamate release was accompanied by a slight inhibition of 14CO2 production from added [14C]glutamate, indicating a simultaneous glutamate uptake and release also under these conditions. Stimulation of glutamate release by 2-oxoisocaproate is followed by a decreased rate of urea and glutamine synthesis from portal ammonia, as a consequence of an increased glutamate release.

Animals↗

PubMed1992

Effect of lectins on hepatic clearance and killing of Candida albicans by the isolated perfused mouse liver.

The isolated perfused mouse liver model was used to study the effects of various lectins on hepatic trapping and killing of Candida albicans. After mouse livers were washed with 20 to 30 ml of perfusion buffer, 10(6) C. albicans CFU were infused into the livers. At the time of recovery, 63% +/- 2% (mean +/- standard error of the mean) of the infused C. albicans CFU were recovered from the liver and 14% +/- 1% were recovered from the effluent for a total recovery of 77% +/- 2%. This indicated that 86% +/- 9% of the original inoculum was trapped by the liver and that 23% +/- 2% was killed within the liver. When included in both preperfusion and postperfusion buffers (0.2 mg of lectin per ml), Ulex europeaus lectin (binding specificity for fucose) decreased hepatic trapping of C. albicans by 37% and eluted trapped C. albicans from the liver only when included in postperfusion buffer. By comparison, treatment of C. albicans with U. europeaus lectin before infusion had no effect on the trapping or killing of yeast cells. When Lens culinaris lectin (binding specificity for mannose) was included in the perfusion buffers, hepatic killing of C. albicans increased by 16% with no significant effect on hepatic killing when yeast cells were treated with L. culinaris lectin before infusion. Forty to 55% of the infused C. albicans were killed when concanavalin A (binding specificities for mannose and glucose), Glycine max (binding specificity for N-acetylgalactosamine), or Arachis hypogea (binding specificity for galactose) lectin was included in the perfusion buffer or when yeast cells were treated with these lectins before their infusion. When C. albicans was treated with concanavalin A at a concentration of less than 0.02 mg/ml, hepatic killing of yeast cells was not significantly increased. The data suggest that a fucose-containing receptor on the surface of either sinusoidal endothelial cells or Kupffer cells is involved in the trapping of C. albicans by the perfused mouse liver. Moreover, lectins with binding specificities for mannose, N-acetylgalactosamine, and galactose increased hepatic killing of C. albicans.

Animals↗

PubMed1985

Influence of pH change on redox state and CCK-induced secretion in isolated perfused rat pancreas.

The isolated perfused rat pancreas was used to examine the influence of the acid-base status of the perfusing solution on the redox states of cytochromes and secretory responses. Lowering the pH in a perfusing solution (pHe) from 7.3 to 6.8 induced simultaneous oxidation of cytochromes aa3, b, and c + c1, and further lowering to 6.0 induced larger oxidation of the cytochromes. Raising the pHe from 7.3 to 8.0 induced reduction of the cytochromes. Continuous stimulation with synthetic C-terminal octapeptide of cholecystokinin (CCK-8) at 100 pM induced the maximum secretory responses (pancreatic juice flow, protein output, and amylase output) during perfusion with the standard solution. The responses were not inhibited at pHe 6.8 but were inhibited significantly at pHe 6.0 or 8.0. The responses induced by stimulation with 20 pM CCK-8 were completely inhibited when pHe was lowered to 6.0 and CaCl2 was removed from the perfusing solution.

Adenosine Triphosphate↗

PubMed1986

Effects of tolbutamide on gluconeogenesis and glycolysis in isolated perfused rat liver.

In isolated perfused livers of 24-h fasted rats, perfused with lactate (2 mM), pyruvate (0.5 mM), or dihydroxyacetone (1 mM), infusion of tolbutamide (0.5 mM) very rapidly (within 3 min) inhibited the rate of gluconeogenesis. However, gluconeogenesis from fructose (1 mM) and glycerol (1 mM) was not affected by tolbutamide. Tolbutamide also inhibited by 30% the rate of 14CO2 production from livers perfused with [1-14C]pyruvate, without altering the rate of 14CO2 production from [2-14C]pyruvate. The rate of hepatic glycolysis from fructose, glycerol, and dihydroxyacetone was also stimulated by 250, 40, and 100%, respectively, during tolbutamide infusion into perfused livers. Tolbutamide also inhibited the endogenous rate of hepatic ketogenesis by 30%. All of the tolbutamide-mediated alterations in hepatic metabolism were reversed upon withdrawal of tolbutamide from the perfusion medium. Decreased hepatic gluconeogenesis from lactate and pyruvate in the presence of tolbutamide was not a consequence of increased pyruvate oxidation via the pyruvate dehydrogenase complex or the tricarboxylic acid cycle.

Animals↗

PubMed1993

Active transport and passive liquid movement in isolated perfused rat lungs.

The isolated perfused liquid-filled rat lung in a "pleural bath" was the model used to study liquid exchange across the lung epithelium. Active transport and passive solute movement between the air space, the vascular perfusate, and the bath result in concentration changes of the three markers (Evans blue-tagged albumin, 22Na+, and [3H]mannitol) instilled in the air space. A mathematical model was developed to estimate the active and passive solute transports and to interpret the results. Rat lungs were perfused at left atrial and pulmonary arterial pressures of 0 and 8 mmHg, respectively. Six rat lung experiments were conducted at 37 degrees C and six at 4 degrees C. The normothermic experiments demonstrate that active transport accounts for 26% of the Na+ movement out of the air space (17.3 +/- 0.7 nm/s) and that passive mechanisms account for the remaining 74% (48.0 +/- 5.7 nm/s). Hypothermia inhibits lung liquid clearance but does not affect passive solute movement, suggesting that lung liquid clearance is effected by active Na+ transport mechanisms.

Animals↗