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 451 records · Page 25Linked to original sources
PubMed1991

Effects of opiates on sodium excretion in the isolated perfused rat kidney.

1. A rat isolated perfused kidney preparation was utilized to define clearly a renal site of action. The variables measured were perfusate pressure and flow, glomerular filtration rate, urine volume, sodium excretion and potassium excretion. 2. Dextromethorphan (3 nmol/L) and dextrorphan (10 nmol/L) reduced sodium excretion in kidneys from rats on either control or high K+ diet, in the absence of any other measured renal effects. Dextromethorphan (10 nmol/L) produced a decrease in glomerular filtration rate as well as a decrease in sodium excretion. Naloxone (1 mumol/L) inhibited the effect of dextromethorphan on sodium excretion but had no effect when administered alone. 3. The levorotatory opiates levorphanol and levomethorphan, the kappa agonist ketocyclazocine and a range of other opiates had no effect on sodium excretion. 4. The results suggest a renal action specific for dextrorotatory opiates. This renal action is consistent with earlier binding studies suggesting preferential recognition of dextrorotatory opiates.

Animals↗
PubMed1972

Species and ionic influences on the accumulation of digitalis glycosides by isolated perfused hearts.

1. The ability of isolated perfused guinea-pig (digitalis-sensitive species) and rat (digitalis-resistant species) hearts to accumulate radio-labelled digitalis glycosides was studied in relation to the ionic composition of the perfusion medium.2. It was observed that in both species much less digoxin was accumulated than was digitoxin or proscillaridin.3. The accumulation of digoxin was markedly inhibited in a low sodium or in high potassium medium. These effects were similar, but relatively less marked, with digitoxin and proscillaridin. Calcium and magnesium removal had relatively smaller effects on the accumulation of both polar and non-polar glycosides.4. The low accumulation of all digitaloids by the rat heart in comparison to the guinea-pig heart may be due to the formation of unstable complexes between the cellular membranes in the rat heart and the various digitaloids used in this study. Although digitaloids have a reduced affinity for rat hearts and rat heart membranes in comparison to guinea-pigs, the order of the accumulation of different glycosides in both species is the same, i.e. much less with polar glycosides than with non-polar glycosides.5. It was concluded that non-polar glycosides such as digitoxin and proscillaridin demonstrate the same ion-dependent accumulation mechanism as do the more polar glycosides such as digoxin and ouabain. In addition, the non-polar glycosides possess high capacity for ion-independent binding presumably due to lipophilic interactions with membranes.

Animals↗
PubMed1990

Cell swelling, co-transport activation and potassium conductance in isolated perfused rabbit kidney proximal tubules.

1. Isolated, perfused rabbit proximal tubules were used to study the effects of activation of the apical membrane sodium co-transporters, and of the effects of osmotically induced cell swelling, upon cell volume, basolateral membrane potential and apparent partial conductance of potassium. 2. Activation of electrogenic apical sodium co-transport caused a depolarization of the basolateral membrane and a reduction of the basolateral apparent potassium transference number. This was followed by a spontaneous partial recovery of potential and increase in apparent potassium transference number. 3. Stimulation of apical sodium co-transport led to a sustained increase in cell volume. 4. A sustained increase in cell volume (of similar magnitude to that seen after activation of apical membrane sodium co-transporters) was also caused by reduction of bath and perfusate osmolality by removal of 89 mmol l-1 mannitol from both lumen and bath solutions. 5. This reduction in bath and perfusate osmolality also led to a basolateral membrane hyperpolarization and an increase in basolateral apparent potassium transference number. 6. These observations support the possibility that some of the partial recovery of basolateral membrane potential (Vb1) during apical sodium co-transport stimulation is due to a cell volume sensitive change in basolateral potassium conductance.

Animals↗
PubMed1990

Net acid transport by isolated perfused inner medullary collecting ducts.

The isolated perfused tubule technique was used to study net acid transport in rat terminal inner medullary collecting duct (IMCD) segments. The stop-flow luminal pH [measured fluorometrically with the acidic form of the pH-sensitive dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein in the lumen] fell 0.35 units below the bath pH in tubules from control rats and 0.53 units below the bath in tubules from deoxycorticosterone-treated rats. Tubules from control rats absorbed bicarbonate and secreted ammonium against concentration gradients, although at low rates. In control rats, 10(-8) M vasopressin added to the bath increased bicarbonate absorption almost threefold. Treatment of rats in vivo with deoxycorticosterone significantly increased the rate of bicarbonate absorption in vitro. In vivo NH4Cl loading also significantly increased bicarbonate absorption. Staining microdissected tubules with acridine orange confirmed that the perfused segments lacked intercalated cells. We conclude that the terminal IMCD spontaneously acidifies the lumen despite an absence of intercalated cells. Bicarbonate absorption appears to be regulated by the same factors that affect net acidification in other collecting duct segments.

Absorption↗
PubMed1982

Differential effect of adenosine and hypoxia on potassium-induced dilation in the isolated, perfused guinea pig heart.

In 13 isolated, perfused guinea pig hearts we determined the coronary flow responses to abrupt elevation of perfusate potassium levels (final concentration 12-16 mM) in the absence and presence of adenosine, and during hypoxic perfusion. Control diastolic coronary flow and spontaneous heart rate averaged 7.85 +/- 0.26 ml/min/g and 249.6 +/- 2.4 beats/min, respectively. Potassium infusion (12-16 mM) in the absence of other intervention did not alter coronary flow significantly. Repeat potassium elevation in the presence of 0.05 and 0.1 microM adenosine (threshold dilating doses) produced respective flow increases of 58 and 43% above normokalemic flow (p less than 0.05). Paradoxically, during hypoxic perfusion (70%, O2 or 45% O2 in the gas phase) potassium did not elevate flow and, in some instances, constricted the vessels. Myocardial oxygen consumption and effluent potassium levels did not change with adenosine or hypoxic perfusion. These results suggest two points: (1) an interaction between potassium ion and adenosine may be important in the regulation of coronary flow and (2) hypoxic dilation in the coronary vasculature may act via a mechanism different from that of adenosine.

Adenosine↗
PubMed1991

The uptake of oestrone from the lumen of the isolated perfused rat gut.

1. In the isolated perfused rat gut oestrone was not taken up from the perfusate but was rapidly taken up from the gut lumen when administered in dimethyl sulphoxide or in 10% acetone in water. 2. Uptake from corn oil was much slower and the rate was concentration-dependent. 3. When given in dimethyl sulphoxide or in aqueous acetone, the residual oestrone in the gut lumen was largely unchanged, with only about 10% being present as the glucuronide. Of the oestrone in the gut perfusate, some 40% was glucuronidated. 4. No evidence was obtained for any reduction or hydroxylation, or for any sulphation, during uptake of oestrone by the gut. 5. No secretion of oestrone or its metabolites into lymph could be detected.

Animals↗
PubMed1990

A modified apparatus for dual, sterilized, isolated perfusion of the rat liver.

The isolated perfused rat liver (IPRL) has proven to be a useful model for the study of physiology and pathology of the liver. For research in nonparenchymal cell (NPC) function that includes measurement of cytokine production (eg, TNF), it is necessary to have a sterilized perfusion system. We have modified the IPRL apparatus so as to be able to perform sterile perfusions of two livers simultaneously. The perfusion apparatus is a recirculating closed system in which the oxygenator is a plastic container separated into two chambers by a fenestrated plastic wall. A disposable macropore filter functions as both a bubble trap and perfusate filter. The sterilization process is done by immersing the various components in Benz-All solution. The tubing is disinfected by irrigation with 10% Clorox followed by 0.9% sodium chloride solution. The perfusate used is filter-sterilized Krebs buffer solution containing 0.5 g Mandol/250 mL perfusate. Not only can two organs be conveniently perfused simultaneously, but the entire system can be reliably sterilized for up to 20 consecutive perfusions. Bile production is higher and more stable with less leakage of intracellular enzymes. Many of the components are disposable and can be altered to suit the needs of a particular experiment.

Animals↗
PubMedDate not supplied

Low extracellular magnesium results in cardiac failure in isolated perfused rat hearts.

Previous studies on isolated blood vessels indicate that acute withdrawal of extracellular magnesium ions ([Mg2+]o) induces calcium-dependent contractile responses, including coronary blood vessels. The present study, using isolated perfused rat hearts, was designed to assess whether low [Mg2+]o could result in cardiac failure and to gain some insight into the mechanism of action. The results show that both the myocardial oxygen consumption (by 29-38%) and oxygen tension in the coronary effluent decreased (by 18-26%) as the [Mg2+]o was decreased stepwise from 1.2 to 0.6, 0.3 and 0.0 mM. Linear-regression analysis of a plot of coronary flow versus the rate of oxygen consumption shows that there is a tendency for a rightward shift of this relationship in low [Mg2+]o and a leftward shift of the curve in elevated [Mg2+]o (4.8 mM). The experiments also show that with low [Mg2+]o, coronary flow declines 20-37%, and cardiac output and stroke volume fall 24-50% accompanied by 3- to 4-fold elevations in lactate production and eventual, irreversible cardiac failure. An interesting finding, of this study, is that the alpha-adrenoceptor constrictor agonist, phenylephrine (1-5 microM), was found to have effects very similar to low [Mg2+]o. This latter finding is consonant with our hypothesis that progressive lowering of extracellular, ionized magnesium initiates progressive coronary vasoconstriction, decreased tissue oxygenation and myocardial ischemia, which given time, in situ, in the intact host can lead to cardiac failure.

Animals↗
PubMed1979

[The influence of clanobutin on bile secretion in the isolated perfused rat liver (author's transl)].

Isolated perfused rat liver was used to characterize the choleretic action of 4-[4-chloro-N-(4-methoxyphenyl)-benzamido]-butyric acid (clanobutin). The dose-dependent increase of the bile flow was associated with an increase of the Na+ secretion. In in vitro studies the drug inhibited the Na+-K+-ATPase of the sinusoidal membrane more than that of the canalicular membrane in a dose-dependent manner. The following hypothesis was proposed to explain the choleretic action of clanobutin. The intracellular Na+ concentration increased due to the inhibition of the sinusoidal Na+-K+-ATPase. This is then compensated by transporting the extra Na+ into the bile. However, it cannot be ruled out that Na+ is transported as counterion during hepatobiliary transport of clanobutin or else its metabolites. The effect of the drug seems to be non-specific since other enzymes of the plasma membrane were also inhibited.

Adenosine Triphosphatases↗
PubMed1989

Pharmacokinetics and pharmacodynamics of atrial natriuretic peptide after bolus and infusion administration in the isolated perfused rat kidney.

We used the isolated perfused rat kidney to test the hypothesis that the renal pharmacokinetics and pharmacodynamics of atrial natriuretic peptide (ANP) are saturable and dependent on the method of administration. Wistar rat kidneys were perfused for 90 min after a bolus dose or continuous infusion of 45, 180, 450 ng of ANP. ANP clearance ranged from 3.27 to 2.28 ml/min after bolus administration. ANP clearance fell after infusion, resulting in a disproportionate increase in the ANP concentration with increasing infusion rate. The ANP half-life was unaffected by dose in the bolus group averaging 18 min. Increasing the ANP dose also increased the amount of Na excreted into the urine, but there were no differences between experimental groups. However, the area under the curve responsible for the natriuresis was 36 to 41% lower after infusion. Exogenous creatinine clearance, renal perfusion pressure and flow and renal vascular resistance were not affected. We conclude that the renal pharmacokinetics of ANP are saturable and are altered by the method of administration due to a down regulation of the ANP receptor. Furthermore, infusion of ANP should result in a greater net natriuresis due to resulting greater ANP concentrations at steady state and an apparent increased sensitivity of the kidney to ANP after infusion.

Animals↗
PubMed1987

Hypoxia impairs conjugation and elimination of harmol in the isolated perfused rat liver.

Although studies in isolated hepatocytes have demonstrated that hypoxia adversely affects drug conjugation, the impact of hypoxia on drug elimination by conjugation in the intact liver has not been defined. This study in the isolated perfused rat liver examines the effect of acute hypoxia on the hepatic elimination of harmol, a phenolic compound eliminated by conjugation without first undergoing oxidative metabolism. In the preparation used in these experiments, harmol glucuronide is the major metabolite (greater than 80%), with the remainder being sulfate. The hypoxic insult consisted of an 80% reduction of hepatic oxygen delivery for 1 hr. During normal oxygenation, a 20-mumol dose was rapidly eliminated (T1/2 = 4.3 +/- 0.8 min; mean +/- S.D., n = 5). A second dose given after 30 min of hypoxia was eliminated much more slowly (T1/2 = 21 +/- 7.9 min, P less than .01). Upon reoxygenation, T1/2 recovered to 4.2 +/- 0.5 min. Similar effects were observed in steady-state experiments, in which perfusate levels rose from 15.7 +/- 1.3 microM to 31.0 +/- 1.6 microM (P less than .005) during hypoxia, indicating a fall in harmol clearance of at least 50%. In each group of experiments, there was a significant reduction in both the formation and elimination of harmol conjugates during hypoxia. Upon reoxygenation, harmol conjugation recovered, but conjugate elimination remained significantly impaired. The authors conclude that acute hypoxia slows the hepatic elimination of harmol by reducing drug conjugation, an effect that is promptly reversed by reoxygenation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1986

Effects of ouabain on the nerve stimulation-evoked release of norepinephrine from the isolated perfused guinea-pig heart.

The isolated perfused guinea-pig heart prelabeled with (-)-[7-3H]-norepinephrine was used to examine the effects of increasing concentrations of ouabain on the sympathetic nerve stimulation-evoked release of endogenous norepinephrine and [3H]norepinephrine in the presence and absence of physostigmine or atropine. The overflow of norepinephrine and [3H]norepinephrine from guinea-pig hearts was measured during postganglionic stimulation of the cardiac accelerator fibers (5 Hz for 60 sec, 2 msec duration, for 300 pulses). Perfusion with 10(-7) M ouabain for 20 min had no effect on the release of norepinephrine or [3H]norepinephrine after nerve stimulation. However, perfusion with either 10(-6) or 3 X 10(-6) M ouabain for 15 min resulted in a significant decrease in the nerve stimulation-evoked release of norepinephrine (44.6 +/- 2.24 and 44.0 +/- 2.17%, respectively) and [3H]norepinephrine (43.8 +/- 1.62 and 44.9 +/- 2.16%, respectively) compared with previous control outputs. Perfusion of hearts with physostigmine (10(-6) M), an acetylcholinesterase inhibitor, or atropine (3 X 10(-6) M), a muscarinic blocking agent, did not alter the release of norepinephrine or [3H]norepinephrine after nerve stimulation. Perfusion with physostigmine during perfusion with 10(-6) M ouabain resulted in a decrease in the release of norepinephrine and [3H]norepinephrine only slightly greater than 10(-6) M ouabain alone, which was not significant, but the release of norepinephrine during stimulations performed after a 45-min washout of 10(-6) M ouabain was decreased significantly when 10(-6) M physostigmine was present. Perfusion of hearts with atropine during perfusion with either 10(-6) or 3 X 10(-6) M ouabain reversed the inhibitory effect of ouabain on the release of norepinephrine and [3H]norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1982

Metabolic studies with an isolated, perfused rat brain preparation.

An unanesthetized, isolated, perfused rat brain, consisting of the skull and its contents with nearly all other tissues removed, has metabolic and electrical activity similar to that of the brain of the intact rat with its blood-brain barrier intact. Its use yielded results that are difficult or impossible to obtain from in vitro preparations or in vivo. With the perfused brain it was shown that mannose can completely replace glucose as metabolic substrate, that insulin has no direct effect on the brain, that in the absence of added substrate glutamate is metabolized to aspartate, that the brain does not metabolize ethanol, and that morphine probably inhibits mitochondrial oxidative activity.

Amino Acids↗
PubMed1986

Tubular reabsorption rates for myoglobin in the isolated perfused rat kidney.

The renal handling of myoglobin has been studied in the isolated perfused rat kidney. Myoglobin was freely filtered. Reabsorption by the renal tubules showed saturation kinetics with a relatively low maximum rate of reabsorption (Tmax) of 27-30 micrograms min-1 g-1 wet wt. at a perfusate concentration of 70-80 micrograms/ml. Myoglobin reabsorption is therefore much less than that reported for immunoglobulin light chain or lysozyme in this model. Large increases in sodium and water excretion produced by omission of oncotic agent from the perfusate did not alter the kinetics of myoglobin reabsorption. The use of bovine serum albumin as oncotic agent in the perfusate prevented the tubular reabsorption of myoglobin. Small amounts of albumin are filtered by the isolated perfused kidney and it is postulated that this albumin interferes with tubular reabsorption of myoglobin.

Absorption↗
PubMed1994

[On the method of hyperthermic chemotherapy by regional isolated perfusion for tumors of lower extremities].

From August 1990 to June 1993, 30 patients with osteosarcoma of lower extremities were treated with chemotherapy by hyperthermic regional isolated perfusion. There were 19 male and 11 female with a mean age of 21 (15-28) years. All of the tumors were located in the lower limbs: 20 on the femora, 9 on the tibiae and 1 on the fibula. Chemotherapy was going on for 60 minutes during hyperthermic regional isolated perfusion. Temperature was kept at 42 degrees C in deep soft tissue around the tumor during perfusion. The results showed that local edema of the limbs were reduced observably, tumors were shrunken and hardened after perfusion. Perimeter of the limbs were decreased and mobility of the limbs increased. Pathological examination indicated that all of the tumors responded well to the chemotherapy by perfusion and 90%-95% of the osteosarcoma cells were destroyed. Two cases were complicated with compression syndrome, and 1 with renal failure. The authors would suggest that hyperthermic regional isolated perfusion is an effective chemotherapeutic method in management of malignant tumors of limbs.

Adolescent↗
PubMed1977

The metabolism of cyclohexanecarboxylic acid in the isolated perfused rat liver.

1. Cyclohexanecarboxylic acid in isolated perfused rat livers was eliminated from the perfusion system by a first-order process. 2. After 6 h, 16% was excreted in bile as cyclohexylcarbonyl beta-D-glucuronide. The remainder was present in the perfusate as unchanged cyclohexanecarboxylic acid (10%), hippuric acid (50%), hexahydrohippuric acid (2%), 3,4,5,6-tetrahydrohippuric acid (2%), cyclohexylcarbonyl-beta-D-glucuronide (2-4%) and benzoic acid (1-2%). Six per cent of the dose was associated with the red blood cell present in the perfusion medium. 3. Unlike the whole animal, the isolated rat liver produced no detectable benzoyl glucuronide. 4. The identity and kinetics of production of the metabolites are consistent with a metabolic pathway previously proposed for cyclohexanecarboxylic acid and shikimic acid.

Animals↗
PubMed1985

Compartmental analysis of the efflux of l-[3H]norepinephrine from isolated perfused rat lungs.

Isolated rat lungs, pretreated with 100 microM pargyline and 100 microM U-0521 (3',4'-dihydroxy-2-methylpropriophenone) to block metabolism of norepinephrine (NE), were perfused with 0.3 microM 3H-labeled l-norepinephrine (1-[3H]-NE) for 30 min. Efflux samples were then collected for 30 min during washout of the tissue with amine-free Krebs solution. Compartmental analysis (nonlinear least-squares regression) of the efflux of tissue l-[3H]NE content vs. time indicates that NE is accumulated in a large slowly equilibrating compartment (t 1/2 = 58.15 +/- 6.84 min) in addition to distribution in the vascular (blue dextran tracer) and extracellular ([3H]sorbitol tracer) fluid compartments of the lung. Pretreatment of the lungs with 100 microM cocaine hydrochloride reduces the total l-[3H]NE space from 7.44 +/- 1.91 to 2.48 +/- 0.23 ml/g (P less than 0.05) by selectively decreasing the size of the slow NE compartment from 6.99 +/- 1.97 to 1.67 +/- 0.14 ml/g (P less than 0.05). The large size, cocaine sensitivity, and long efflux half time of this compartment suggest that neuronal uptake contributes to the pulmonary vascular inactivation of l-[3H]NE.

Animals↗
PubMed1988

Effects of polidocanol as a constituent of a venous sclerosing agent on cardiac electrical activity. Studies on the isolated perfused heart and papillary muscle of the guinea pig and on the isolated sinus node of the rabbit.

The effects of a frequently used sclerosing agent (Sotravarix 6%, main constituent polidocanol 60 mg/ml = 0.1 mol/l) on the electrical activity of the isolated perfused guinea pig heart and on transmembrane potential of isolated papillary muscle and sinus node were studied. Application of the sclerosing agent in a dilution of 1:40,000 (corresponding to polidocanol 2.6 x 10(-6) mol/l) caused a significant decrease in frequency (-27%) and (at constant frequency) a significant delay of the atrioventricular as well as of the intraventricular conduction (+105% or + 210%, resp. n = 4). These effects were only slightly reversible in a 30 min wash-out period. In the isolated papillary muscle, the sclerosing agent (dilution 1:10,000; polidocanol 1 x 10(-5) mol/l) decreased the maximum rate of rise of the action potential and shortened its duration, both by about 10%. In the isolated sinus node the same dilution decreased the spontaneous rate by about 8% mainly by reducing the diastolic depolarization rate (-18%). The effects of the sclerosing agent are attributable to the influence of polidocanol and consist in a blockade of the fast sodium channels (local anesthesia) and in additional inhibitory effects on calcium and/or potassium conductance.

Action Potentials↗