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 541 records · Page 30Linked to original sources
PubMed1989

Airway responsiveness in isolated perfused rat lungs: effect of thoracic irradiation.

We developed techniques for assessing airway reactivity in isolated perfused rat lungs by measuring the lung mechanics changes produced by injection of ACh into the pulmonary circulation. Lung resistance (RL) and dynamic compliance (Cdyn) changed in a dose-response fashion after ACh. We used the preparation to examine the effect of thoracic irradiation on airway responsiveness and pulmonary inflammation. Groups of rats were studied after sham irradiation or 24 h or 72 h after a single dose of 1500 rads. Thoracic irradiation did not alter baseline lung mechanics, but did increase the responsiveness of rat lungs to ACh 72 h after radiation. Radiation was not associated with an increase in neutrophils in lung lavage, airways or peripheral lung tissue. We conclude that thoracic irradiation alters airways reactivity without causing overt pulmonary inflammation, and that isolated perfused lungs can be useful for measurement of airway reactivity.

Acetylcholine↗
PubMed1975

Arrhythmias and inhibition of noradrenaline uptake caused by tricyclic antidepressants and chlorpromazine on the isolated perfused rabbit heart.

1. Isolated rabbit hearts were perfused with a modified Tyrode solution containing noradrenaline in concentrations increasing stepwise from 5.9 nM to 5.9 muM at 5 min intervals. This dose regime was applied twice before and once 20 min after starting perfusion with one of 9 tricyclic drugs. Ventricular rate and right atrial and ventricular tensions were recorded using the transverse method. 2. Infusions of noradrenaline evoked ventricular arrhythmias in hearts perfused with amitriptyline 4.8 muM, chlorpromazine 5.0 muM, desipramine 5.0 muM, dibenzepine 34.7 muM, doxepin 4.7 muM, imipramine 4.7 muM, noxiptiline 9.1 muM and opipramole 9.2 muM. The incidence of arrhythmias increased with the concentration of noradrenaline applied and the dose of tricyclic drug administered. Whenever arrhythmias had started they continued as long as noradrenaline was infused. Noradrenaline failed to produce arrhythmias in hearts not exposed to drugs and after iprindole 4.7 muM or cocaine 2.9-18 muM. 3. Propranolol 0.1 muM inhibited the incidence of arrhythmias after doxepin 4.7 muM plus noradrenaline 5.9-190 nM. 4. Neuronal uptake of exogenous noradrenaline in the rabbit heart was inhibited by the tricyclic drugs in the following order of declining p potency: doxepin, noxiptiline, amitriptyline, desipramine, chlorpromazine, imipramine, dibenzepine, opipramole and iprindole. 5. Among tricyclic drugs the potency to inhibit amine uptake is related to the incidence of arrhythmias evoked by a submaximal concentration of noradrenaline. It appears, however, that these two parameters are not causally linked. 6. The isolated rabbit heart perfused with noradrenaline might be used as a model for testing the arrhythmogenic actions of tricyclic drugs and the treatment of such arrhythmias.

Animals↗
PubMed1976

Tryptophan metabolism in the isolated perfused liver of the rat: effects of tryptophan concentration, hydrocortisone and allopurinol on tryptophan pyrrolase activity and kynurenine formation.

1 The effect of tryptophan concentration on the rate of kynurenine appearance and tryptophan disappearance in the medium perfused through the isolated liver of the rat has been investigated. The effect of pretreatment of the rat with hydrocortisone or allopurinol was also examined, together with the effects of these treatments on liver tryptophan pyrrolase activity measured in vitro at the beginning and end of perfusion. 2 Hydrocortisone (5 mg/kg) injection 3 h before perfusion resulted in a four-fold increase in kynurenine production by the liver during perfusion with a medium containing either 0.1 mmol/1 or 1.0 mmol/1 tryptophan. Injection of allopurinol (20 mg/kg) together with hydrocortisone and addition of allopurinol (4 mg/100 ml) to the medium abolished the hydrocortisone-induced rise of kynurenine in the 0.1 mmol/tryptophan medium but not the 1.0 mmol/1 tryptophan medium. 3 Injection of cycloheximide (30 mg/kg) with hydrocortisone (5 mg/kg) 3 h before perfusion inhibited the hydrocortisone-induced rise of kynurenine production and the increase in pyrrolase activity measured in vitro both before and at the end of perfusion with 1.0 mmol/1 tryptophan. This last result suggests that protein synthesis is involved not only in hydrocortisone induction of pyrrolase but also in substrate induction. 4 Kynurenine production in the 1.0 mmol/1 tryptophan medium was less in both saline- and hydrocortisone-treated older rats (335-450 g) compared to younger rats (180-220 g). In agreement with a previous study, pyrrolase activity in vitro was also lower in both saline- and hydrocortisone- treated older rats at the beginning of the perfusion although activity had risen equally in both young and older rats at the end of perfusion. 5 There was little correlation between the rate of tryptophan disappearance from the medium and the activity of tryptophan pyrrolase either as measured in vitro or as indicated by the rate of kynurenine production. 6 In general, the production of kynurenine in the medium at the end of the 60 min perfusion was indicative of in vitro pyrrolase activity at the start of the perfusion. 7 It is concluded that while in vitro pyrrolase assay does not give a quantitative index of kynurenne production, it does provide a qualitative index. Furthermore, if kynurenine production in the isolated perfused liver of the rat is indicative of in vivo pyrrolase activity, then hydrocortisone must induce pyrrolase activity in vivo.

Age Factors↗
PubMed1983

Glomerular filtration in the isolated perfused kidney. II. Glomerular hemodynamics.

Glomerular hemodynamics were studied of isolated perfused kidneys of 12-wk-old normotensive (NR) and spontaneously hypertensive (SHR) rats, using Pluronic F108 (BASF, Wyandotte, MI, USA) as a plasma expander. Glomerular filtration rate (GFR), proximal tubular hydrostatic pressure (PT) and glomerular capillary hydrostatic pressure (PGC) were approximately linearly related with renal perfusion pressure. PGC measured directly by micropuncture was comparable to PGC calculated from other parameters of glomerular dynamics using pore theory. We conclude that GFR in isolated kidneys perfused with Pluronic F108 is lower than in vivo, mainly as a result of an increase in PT. This rise in tubular pressure is due to an increased urine flow rate and an elevated tubular fluid viscosity. The difference in glomerular dynamics between NR and SHR kidneys is the result of an increased preglomerular vascular resistance in SHR, possibly due to an adaptive hypertrophic reaction to a sustained hypertension.

Animals↗
PubMed1989

Effect of procainamide on renal tubular transport of cimetidine in the isolated perfused rat kidney.

The effect of procainamide on renal tubular transport of cimetidine was studied in isolated perfused rat kidney based on the multiple indicator dilution (MID) technique. T-1824-labeled albumin (a vascular reference), [14C]creatine (an extracellular reference), and [3H]cimetidine were rapidly injected into the renal artery of isolated perfused rat kidney in the presence or absence of procainamide (100 microM) in the perfusate, and normalized outflow-time patterns were secured from rapidly sampled renal perfusate. A distributed two-compartmental model was fitted to the dilution data by non-linear least-squares regression, and the influx, efflux and sequestration rate constants were estimated. Net transport and influx processes of cimetidine were competitively inhibited by procainamide (PA), while the efflux and sequestration processes were increased. The increase in the values of the efflux and sequestration rate constants by addition of procainamide may be explained by the increase in the tissue binding of cimetidine. However, these three processes were not significantly affected by p-aminohippurate (PAH). These results suggest that both cimetidine and procainamide are secreted into the lumen by an organic base transport mechanism in the perfused kidney, in which the spatial organization and cell polarity of the kidney are maintained.

Albumins↗
PubMed1992

Biotransformation of the hexachlorobutadiene metabolites 1-(glutathion-S-yl)-pentachlorobutadiene and 1-(cystein-S-yl)-pentachlorobutadiene in the isolated perfused rat liver.

1. The first step in the bioactivation of the nephrotoxin hexachlorobutadiene is the biosynthesis of 1-(glutathion-S-yl)-1,2,3,4,4-pentachloro-1,3-butadiene (GPCB). GPCB formed in the liver is secreted into bile, may be reabsorbed in the gut, intact or after hydrolysis to 1-(cystein-S-yl)-1,2,3,4,4-pentachloro-1,3-butadiene (CPCB), and undergo enterohepatic circulation or translocation to the kidney. Hepatic uptake and metabolism of GPCB and CPCB may thus influence the disposition of these S-conjugates. We therefore studied the metabolism and uptake of CPCB and GPCB in the isolated perfused rat liver. 2. Dose-dependent uptake of GPCB and CPCB from the perfusion medium by isolated perfused liver was demonstrated; CPCB is cleared from the perfusion medium to a much higher extent than GPCB. 3. GPCB and CPCB are intensively biotransformed to biliary metabolites. These metabolites were identified by thermospray mass spectrometry as products of the conjugation reaction of GPCB and CPCB with glutathione and subsequent hydrolysis of the glutathione moieties. 4. Hepatic biosynthesis of 1-(N-acetyl-L-cystein-S-yl)-1,2,3,4,4-pentachloro- 1,3-butadiene from CPCB was only a very minor pathway in GPCB and CPCB metabolism in liver. 5. The results indicate that hepatic biosynthesis of mercapturic acids may not contribute to the disposition of S-conjugates formed from hexachlorobutadiene in vivo and that GPCB may be, at least in part, delivered intact to the kidney.

Animals↗
PubMed1996

Vascular effects of [Arg8]vasopressin in the isolated perfused rat kidney.

The renal vascular effects of [Arg8]vasopressin (vasopressin) were investigated in the isolated perfused rat kidney. Vasopressin (0.01-3 nM) elicited a dose-dependent vasoconstriction in kidneys from Sprague Dawley rats, with a EC50 value of 0.206 +/- 0.044 nM. Inhibition of nitric oxide synthase by N omega-nitro-L-arginine (100 microM) shifted the vasopressin-induced vasoconstrictor response curve to the left. Inhibition of cyclooxygenase by indomethacin (10 or 30 microM) blunted the constriction induced by low concentrations of the peptide. Vasopressin, like angiotensin II but not noradrenaline, induced tachyphylaxis, SR 49059 ((2S)1-[(2R,3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene- sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2- carboxamide) (1-30 nM), a new potent and selective non-peptide vasopressin V1A receptor antagonist, shifted the concentration-response curve for vasopressin to the right without decreasing the maximum contraction. Antagonism became competitive with a pA2 value (+/- S.D.) of 9.72 +/- 0.20 during inhibition of nitric oxide release. [Mpa1,D-Arg8]Vasopressin (desmopressin; 0.1-100 nM), or vasopressin (0.01-1 nM) after blockade of the vasopressin V1A receptor by SR 49059, induced no vasopressin V2 receptor-related renal relaxation in kidneys with vascular tone previously restored by noradrenaline or prostaglandin F2 alpha. These findings indicate that in the isolated perfused rat kidney vasopressin is a potent renal vasoconstrictor. The constriction depends on activation of smooth muscle vasopressin V1A receptors and is modulated by endothelial nitric oxide but not by prostacyclin or vasopressin V2 receptor-related vasodilation.

Angiotensin II↗
PubMed1988

Effects of hydrocortisone on glucose- and cholecystokinin-induced insulin release from the isolated perfused rat pancreas.

The acute and chronic effects of hydrocortisone on insulin secretion were examined in the isolated perfused rat pancreas. In the first part of this study, the chronic effects of hydrocortisone on insulin release were examined using isolated perfused pancreas prepared from rats that had been given subcutaneous injections of hydrocortisone at doses of 1.25, 2.5, 5.0, and 10.0 mg/kg body weight once daily for 7 days. Hydrocortisone treatment led to a dose-dependent increase in insulin secretion in response to 8.3 mM glucose. The insulin response to 100 pM cholecystokinin (CCK-8) was also significantly higher in the hydrocortisone-treated rats than in the control group. However, the increment of insulin level over the value before CCK-8 addition in rats treated with hydrocortisone was not significantly different from that in the control rats. In the second part, the acute effects of hydrocortisone on insulin release were studied. Hydrocortisone (17-hydroxycorticosterone) at a concentration of 100 microM caused significant inhibition of the stimulatory effect of CCK-8 on insulin secretion. The inhibition started within 1 min of the beginning of hydrocortisone administration and ceased immediately after the termination of its infusion. We have demonstrated in this study a dual effect of hydrocortisone on insulin release: first, the potentiation of the insulin secretion stimulated by glucose but not by CCK-8 and, second, the inhibition of CCK-8-stimulated insulin secretion.

Animals↗
PubMed1997

Intraislet regulation of pancreatic polypeptide secretion in the isolated perfused rat pancreas.

The present study is to determine if intraislet insulin or somatostatin regulate pancreatic polypeptide (PP) secretion in the isolated perfused rat pancreas by infusing insulin or somatostatin antisera. Isolated rat pancreata were stimulated with either 16.7 mM glucose (G) alone, G with antisomatostatin antibody (G + SA), or G with antiinsulin antibody (G + IA). G inhibited PP secretion -22 +/- 9.5 pM below basal, a decrease of 9 +/- 6.3% (n = 6; p = NS), G + IA inhibited PP secretion -10 +/- 27.2 pM below basal, a decrease of 20 +/- 15% (n = 7, p = NS), and G + SA stimulated PP secretion 18 +/- 7.1 pM above basal, an increase of 26 +/- 5% (n = 6; p < 0.05). G stimulated insulin secretion 3,144 +/- 210 pM above basal (n = 6, p < 0.05), and G + SA stimulated insulin secretion 2,695 +/- 195 pM above basal (n = 7; p < 0.05 vs. baseline, p = NS vs. G alone). G stimulated C-peptide secretion 886 +/- 175 pM above basal (n = 6; p < 0.05), G + SA stimulated C-peptide secretion 847 +/- 102 pM above basal (n = 7; p < 0.05, p = NS vs. G alone), and G + IA stimulated C-peptide secretion 834 +/- 93 pM above basal (n = 7; p < 0.05, p = NS vs. G alone). These data demonstrate that infusion of SA results in significant stimulation of PP secretion during high-G infusion, whereas IA has no effect. Infusions of SA or IA at the doses used have no effect on G-stimulated insulin or C-peptide secretion. This suggests that intraislet somatostatin may be an inhibitory regulator of PP secretion in the isolated perfused rat pancreas.

Animals↗
PubMed1984

Isolated perfused lung preparation for studying altered gaseous environments.

The isolated perfused lung (IPL) preparation is ideally suited to investigate lung dynamics and cellular function, and is easily adapted to investigating biochemical and physiological responses to environmental insults. The IPL offers several advantages which permit one to study endothelial/epithelial interactions that are often disrupted with other model systems (e.g., isolated cells, minces, slices, homogenates, etc.). The IPL developed in our laboratory was devised for the rat lung and allows four lungs to be perfused simultaneously in which control over ventilation, flow, pressure, pH, PO2 and PCO2 can be maintained. Isolated lungs perfused for 1 to 2 hr at a flow rate of 10 mL/min exhibit less that 2% weight gain, maintain normal ATP levels, and exhibit linear substrate uptake. Mechanisms leading to changes in vascular and airway resistance, lipid metabolism, vasoactive hormones, blood gases and changes in vascular permeability mediated by environmental insults can be quantified in the IPL preparation.

Adenosine Diphosphate↗
PubMed1989

Effects of neuromedin B on insulin and glucagon release from the isolated perfused rat pancreas.

The effect of neuromedin B (NMB) on insulin and glucagon release was studied in isolated perfused rat pancreas. Infusion of NMB (10 nM, 100 nM and 1 microM) did not affect the insulin release under the perusate conditions of 5.5 mM glucose plus 10 mM arginine and 11 mM glucose plus 10 mM arginine, although 10 nM NMB tended to slightly suppress it under the perfusate condition of 5.5 mM glucose alone. The degree of stimulation of insulin release provoked by the addition of 5.5 mM glucose to the perfusate was not affected by the presence of 10 nM NMB. The glucagon release was slightly stimulated by the infusion of 100 nM and 1 microM NMB but not by 10 nM NMB under the perfusate condition of 5.5 mM glucose plus 10 mM arginine. The effect of C-terminal decapeptide of gastrin releasing peptide (GRP-10) was also examined and similar results were obtained; 10 nM and 100 nM GRP-10 did not affect insulin release and 100 nM GRP-10 stimulated glucagon release under the perfusate condition of 5.5 mM glucose plus 10 mM arginine. The present results concerning glucagon release are consistent with the previous results obtained with isolated perfused canine and porcine pancreas. However, the results regarding insulin release are not. Species differences in insulin release are also evident with other neuropeptides such as substance P and the mechanism of such differences remains for be clarified.

Animals↗
PubMedDate not supplied

Volume-regulatory potassium release from isolated perfused rat kidney.

The present study has been performed to test for cell volume regulatory potassium release from the isolated perfused rat kidney exposed to hypotonic perfusate and for its sensitivity to potassium channel blocker barium and calcium channel blocker verapamil. Replacement of 25 mmol/l NaCl with 50 mmol/l mannitol has little effect on effluent potassium activity, whereas subsequent omission of mannitol from the perfusate leads to a transient increase of effluent potassium activity, reflecting volume regulatory potassium release. Barium (1 mmol/l) leads to a marked transient decrease of effluent potassium activity, pointing to net cellular uptake of potassium. Verapamil (1 mumol/l) leads to a slight decrease of effluent potassium activity. Both barium and verapamil virtually abolish the rapid, transient increase of effluent potassium activity upon exposure to hypotonic perfusates. Thus, the substances either block or markedly retard volume regulatory potassium release. The apparent renal vascular resistance is transiently increased by exposure to hypotonic perfusates and by barium, but is reduced by verapamil. Cell volume regulation of isolated perfused mouse straight proximal tubules is retarded but not abolished by verapamil (0.1 mmol/l). In conclusion, cellular potassium release from rat kidney can be determined by continuous measurement of effluent potassium activity. The volume regulatory potassium release and cell volume regulation are impaired by both barium and verapamil. The persisting cell volume regulation could be due either to slow potassium release and/or some mechanism independent of potassium.

Animals↗
PubMed2002

Naftidrofuryl exerts antiserotonergic but no endothelin-receptor blocking effects in AS4.1 cells, juxtaglomerular cells and isolated perfused rat kidneys.

Naftidrofuryl, a 5-hydroxytryptamine 2 (5-HT 2 ) serotonergic receptor antagonist with vasodilator effects, has successfully been used for intermittent claudication, some forms of dementia, and glaucoma. Recently, an additional mode of action of naftidrofuryl (i.e., mixed endothelin receptor antagonism) has been suggested. However, in the current study naftidrofuryl was unable to block endothelin-3-induced free intracellular calcium increases, in contrast to a mixed endothelin receptor antagonist, bosentan. The inhibition of forskolin-induced renin secretion by endothelin-3 in primary cultures of mouse juxtaglomerular cells and by endothelin-1 in the isolated perfused rat kidney could not be blocked by naftidrofuryl. Naftidrofuryl was unable to block marked endothelin-1-induced renal vasoconstriction in isolated perfused rat kidney. In contrast, naftidrofuryl markedly attenuated serotonin-induced renal vasoconstriction and nearly completely blocked serotonin's renin inhibitory properties in isolated perfused rat kidney. The present results suggest that naftidrofuryl is a potent antagonist of serotonin's renal effects, but has no endothelin receptor-blocking properties.

Animals↗
PubMed1991

An ex vivo model for the study of tumor metabolism by nuclear magnetic resonance: characterization of the phosphorus-31 spectrum of the isolated perfused Morris hepatoma 7777.

We have developed an isolated perfused tumor model to study the metabolism of solid tumors by nuclear magnetic resonance spectroscopy. Morris hepatomas (7777) were implanted in the inguinal region of Buffalo rats, such that they developed an isolated blood supply. These tumors were perfused with a RBC perfusate, removed from the animal, and studied by 31P nuclear magnetic resonance spectroscopy. ATP levels, as determined from the spectra, were stable for as long as the tumors were maintained in the magnet (7 h) only if the perfusate contained inosine, adenosine, and insulin. The adenosine and inosine were also required for recovery from ischemia. Under these conditions, ischemia did not result in a change in tumor pH. The gamma nucleoside triphosphate resonance was significantly larger than the beta nucleoside triphosphate resonance in spectra of some of the perfused tumors, suggesting that ADP above about 300 nmol/g wet weight was not complexed in these tumors. The adenylate levels determined from extracts, O2 consumption, histology, and 31P nuclear magnetic resonance spectra of extracts of perfused tumors and tumors in situ were all similar, indicating the perfused tumor is a reasonable model of the tumor in vivo.

Adenosine Diphosphate↗
PubMed1992

Disparate effects of calcium channel blockers on pressure dependence of renin secretion and flow in the isolated perfused rat kidney.

Using the model of isolated perfused rat kidneys this study was performed to investigate whether or not voltage-operated calcium channels are essentially involved in the pressure control of renin secretion from the kidneys. At a perfusion pressure of 100 mm Hg (13.3 kPa) renin secretory rates were 4.2 +/- 0.7 (ng angiotensin I h-1) min-1 g-1. Stepwise reduction of renal perfusion pressure to 80, 60, and 40 mm Hg (10.6, 8.0, 5.3 kPa) resulted in an increase of renin release yielding a 30-fold stimulation at 40 mm Hg vs 100 mm Hg. Increasing the perfusion pressure above 100 mm Hg did not further significantly decrease renin secretion. The perfusate flow rate was also pressure-dependent. Flow rates increased linearly with pressure and reached a plateau at 100 mm Hg, which was maintained up to 160 mm Hg (21.3 kPa). The averaged flow rate at the plateau was 15.5 ml min-1 g-1. In the presence of the three different calcium antagonists nifedipine (5 microM), nitrendipine (3 microM) and verapamil (5 microM), myogenic autoregulation of flow was abolished as indicated by the rise of the pressure/flow curve between 40 and 160 mm Hg. At the same time, however, these calcium channel blockers did not alter the relationship between perfusion pressure and renin secretion. Moreover, the calcium channel agonist Bay K 8644 (5 microM) caused a strong and long-lasting vasoconstriction, without changing renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Roles of in vitro- and in vivo-administered histamine and serotonin in compound 48/80-induced gastric acid secretion in isolated, perfused rat stomach.

In this investigation, an isolated, perfused rat stomach system was used to elucidate the roles of histamine, serotonin, and the action of cimetidine, methysergide, and propranolol in relation to the in vivo and in vitro administration of compound 48/80. While histamine administered both in vivo and in vitro stimulated acid secretion in the perfused rat stomach, serotonin, added in vitro, inhibited histamine-induced gastric acid secretion. Cimetidine, given either in vivo or in vitro, blocked histamine-induced acid secretion, and methysergide, but not propranolol, reversed the serotonin-induced inhibition of histamine-stimulated acid secretion. Compound 48/80, given in vitro, caused gastric acid secretion that was blocked by pretreatment with cimetidine. Administered in vivo, however, compound 48/80 inhibited both basal and histamine-stimulated acid secretion. This inhibition was partially reversed by pretreatment with methysergide. The absence of inhibition of acid secretion by in vitro-administered compound 48/80 may be related to the timing of the serotonin effect. When serotonin was given prior to histamine, it blocked acid secretion, whereas no inhibition occurred when serotonin was administered together with histamine. None of the other agents investigated affected basal acid secretion.

Animals↗
PubMed1979

Uptake of [14C]choline and incorporation into lung phospholipid by the isolated perfused rat lung.

We have used the isolated perfused lung (IPL) preparation from the rat to determine whether uptake of choline from the vascular compartment could limit the rate of synthesis of phosphatidyl-choline (PC). The uptake of choline was rapid and did not saturate at a concentration of 10 mM. The rate of incorporation of choline into phospholipid was saturated above 0.1 mM choline. Whereas, uptake and incorporation were depressed at 4 C, uptake was neither dependent on the extracellular sodium concentration nor inhibited by equimolar concentrations of hemicholinium-3 (HC-3). We could find no evidence that uptake might limit synthesis of lung lecithin and conclude that uptake is either by free diffusion, or by a carrier-mediated process with a very high Km.

Animals↗