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 1,423 records · Page 79Linked to original sources
PubMed1993

Effect of intestinal inhibitory peptides on vagally induced secretion from isolated perfused porcine pancreas.

Several gastrointestinal peptides inhibit pancreatic secretion in intact animals, but fail to do so in isolated pancreas preparations. Using isolated perfused porcine pancreas with intact innervation, we studied the influence of such peptides (somatostatin, peptide YY, glucagon-like peptide-1, oxyntomodulin, neuropeptide Y, galanin, and calcitonin gene-related peptide) on vagally induced secretion and on release of vasoactive intestinal polypeptide (VIP), a neuropeptide involved in fluid and bicarbonate secretion. In control experiments electrical vagus stimulation increased flow of juice from 0.9 +/- 0.1 to 37.3 +/- 5.6 ml/h and protein output from 43 +/- 5 to 1,244 +/- 336 mg/h (mean +/- SD). With somatostatin-14 at 10(-10) mol/L, the fluid response was reduced to 64 +/- 11% of controls, protein concentration to 78 +/- 3.8%, and protein output to 50 +/- 5% (p < 0.05). At 10(-8) M the response was almost abolished. VIP release, which in control experiments increased from 0.2 +/- 0.05 to 2.1 +/- 0.4 pmol/min, was similarly reduced (p < 0.01). Galanin at 10(-8) M inhibited the fluid response to 54 +/- 7% of controls, protein output to 51.7 +/- 11%, and VIP release to 54 +/- 6% (p < 0.01). None of the other inhibitory peptides affected vagus responses. It is concluded that somatostatin and galanin inhibit pancreatic secretion through interaction with intrapancreatic ganglia. The other peptides act on extrapancreatic, possibly central sites.

Animals↗
PubMed1977

Coronary reactions to cardiac hyperactivity and to hypoxia in isolated perfused heart of rat.

1. Continuous recording of cardiac force of contraction, heart rate and coronary flow from isolated perfused hearts of rats was used to study coronary reactions: (a) to cardiostimulation with noradrenaline, CaCl2, or electrically induced tachycardia; (b) to short duration stoppage of coronary inflow (hypoxia). 2. The heart rate was controlled by electrical pacing. Coronary vasodilatation resulted from cardiostimulation or hypoxia. This coronary response was greater at higher heart rates. 3. In parallel experiments administration of noradrenaline to hearts paced at different frequencies resulted in a rate-dependent elevation of adenosine-3',5'-cyclic monophosphate (cyclic AMP). 4. Duration of hypoxia leading to different degrees of reactive hyperaemia did not change the cardiac cyclic AMP levels. 5. Coronary vasodilatation due to increased cardiac metabolism produced by noradrenaline, Ca2+ or tachycardia was enhanced by the phosphodiesterase inhibitors diazoxide and papaverine while it was inhibited during the administration of prostaglandin E2.6. Reactive hyperaemia was unaffected by diazoxide, papaverine or prostaglandin E2. 7. Catecholamine depletion by reserpine did not influence metabolic coronary dilatation nor the reactive hyperaemic responses. 8. We postulate that there are at least two types of coronary reactions: one in response to hypoxia, 'reactive hyperaemia', and another resulting from cardiac hyperactivity, 'metabolic coronary dilatation'. The latter, blocked by prostaglandin E2 and enhanced by diazoxide or papaverine, would be triggered by cyclic AMP while reactive hyperaemia would result from other mechanisms.

Animals↗
PubMed1991

Renal handling and effects of S(+)-ibuprofen and R(-)-ibuprofen in the rat isolated perfused kidney.

1. The renal handling and effects of S(+)- and R(-)-ibuprofen have been studied in the isolated perfused kidney (IPK) of the rat. 2. Both ibuprofen enantiomers were extensively reabsorbed and accumulated in the kidney in a concentration-dependent manner. No pharmacokinetic differences were observed between the two enantiomers. 3. S(+)-ibuprofen concentrations ranging from 0.25 to 25 micrograms ml-1 (1.2 to 120 microM) caused a decrease in urinary flow, glomerular filtration rate (GFR) and electrolyte excretion. Urinary pH and excretion of glucose were not influenced. R(-)-ibuprofen concentrations ranging from 2.5 to 25 micrograms ml-1 (12 to 120 microM) also decreased urinary flow and electrolyte excretion. This decrease, however, was less than observed with S(+)-ibuprofen. GFR, urinary pH and glucose excretion were not affected by R(-)-ibuprofen. Prostaglandin E2 (PGE2) concentrations of 133 ng ml-1 reversed the effects on renal function of both enantiomers. 4. Very high S(+)- and R(-)-ibuprofen concentrations (greater than 400 micrograms ml-1) resulted in an increase in urinary flow and fractional excretion of sodium, chloride, potassium, glucose and calcium. 5. It is concluded that the pharmacokinetic behaviour of ibuprofen in the kidney is not stereoselective. Relatively high concentrations of both enantiomers increased the urinary flow and electrolyte excretion in a nonstereoselective manner. Lower concentrations of S(+)-ibuprofen decreased urinary flow and electrolyte excretion. The pharmacologically inactive R(-)-ibuprofen was also able to affect renal function in a similar way, but at different concentrations. These effects on renal function are probably caused by inhibition of PGE2 synthesis.

Animals↗
PubMed1994

Modulation by endogenous prostanoids of the vasoconstrictor activity of endothelin-1 in the canine isolated, perfused spleen.

1. Endothelin-1 (ET-1, 0.4-200 pmol) was injected into the arterial circuit of the isolated perfused spleen of the dog in which splenic arterial perfusion pressure and spleen weight were recorded continuously. 2. Serial collection was made of splenic venous effluent before and after intra-arterial injection of ET-1 and assayed by direct radioimmunoassay for prostaglandin E2 (PGE2), 6-oxo-PGF1 alpha and thromboxane B2 (TXB2). 3. ET-1 caused graded arterial vasoconstriction of prolonged duration with small reductions in spleen weight at higher doses. 4. ET-1 cause a dose-related release of PGE2, 6-oxo-PGF1 alpha and TXB2 into the splenic venous effluent. The mean peak increase above the basal levels following 200 pmol of ET-1 was 800% for PGE2, 233% for 6-oxo-PGF1 alpha and 205% for TXB2. 5. Intra-arterial infusion of indomethacin significantly reduced the basal release of all three eicosanoids and significantly elevated the basal splenic vascular resistance. The release of all three eicosanoids in response to ET-1 and adrenaline (Ad) was significantly reduced by indomethacin and the accompanying increases in the splenic arterial vascular resistance were significantly potentiated at low doses of ET-1. The splenic arterial vascular responses to Ad were unchanged by indomethacin infusion. 6. These results indicate that the release of eicosanoids may modulate the splenic vascular responses to ET-1.

Animals↗
PubMed1989

Volume-regulatory K+ fluxes in the isolated perfused rat liver: characterization by ion transport inhibitors.

Net hepatic release and uptake of K+ were examined in isolated perfused rat livers subjected to a 10-min period of hypotonic stress. Effluent Na+, K+, and Ca2+ activities were monitored throughout. Initiation and termination of hypotonic stress triggered sharp transient (less than 1 min) changes in effluent ion activities that indicated net water movement into and out of the liver, respectively. In addition, hypotonic stress caused a large transient net release of hepatic K+, whereas return to isotonicity triggered a transient net hepatic K+ uptake. The hypotonically induced K+ release was inhibited by 2 mM barium (95%) and by 1 mM quinine (60%). Net K+ influx, on the other hand, was inhibited by 1 mM ouabain (100%) and by 1 mM amiloride (50%). Osmotically induced K+ fluxes were not significantly affected by bicarbonate removal and were only partially inhibited by 0.1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or bumetanide. The results suggest that K+ conductance increases during hypotonic stress, whereas return to isotonicity induces a ouabain-sensitive K+ uptake partly because of increased Na+-H+ exchange. These mechanisms probably participate in regulatory volume decrease and regulatory volume increase, respectively.

Amiloride↗
PubMed1976

Regulation of avian insulin secretion by isolated perfused chicken pancreas.

Chicken insulin secretory responses to glucose, glucagon, tolbutamide, and lack of Mg2+ were measured using isolated perfused in situ chicken pancreata. Although elevating perfusate glucose concentration from 100 to 250 mg/100 ml failed to increase insulin release, 500 mg glucose/100 ml provoked a transient 5-min insulin response. Additionally, 700 mg glucose/100 ml resulted in both a transient response and subsequent elevation in secretory rate that continued throughout the following 50-min stimulatory period. Glucagon (500 microgram/ml) and omission of perfusate Mg2+ potentiated glucose-stimulated insulin output by 6 and 25%, respectively. A faster release of insulin (less than 1 min) occurred during tolbutamide infusion (0.13 mg/ml) than with either 500 or 700 mg glucose per 100 ml (2-3 min); however, secretory rates declined to near basal levels within 5 min. Mammalian-like insulin responses to glucose, glucagon, Mg2+ lack, and tolbutamide suggest similarities between avian and mammalian beta-cell insulin secretory mechanisms. Nevertheless, the relatively high chicken insulin release threshold and low insulin output to glucose indicate that chicken pancreata are relatively glucose insensitive.

Animals↗
PubMed1989

Time-dependent effects of extraluminally-applied oxyhemoglobin and endothelial removal on vasodilator responses in isolated, perfused canine basilar arteries.

The effects of oxyhemoglobin (oxyHb) and removal of the endothelium have been measured in isolated, perfused canine basilar arteries treated with intraluminal vasodilator drugs. In preparations with an intact endothelium, acetylcholine (ACh) produces a biphasic response, where a small vasodilation precedes a vasoconstriction. Calcium ionophore A23187 and thimerosal induce a vasodilation at low doses and a biphasic response at high doses. Sodium nitroprusside (SNP) evokes only a vasodilation. Extraluminally applied oxyHb itself produces a transient vasoconstriction and then a gradual increase in perfusion pressure. After this treatment, the vasoconstriction to ACh was enhanced as was the vasodilation to SNP. Significant attenuation of the vasodilator action of A23187 and thimerosal was also observed. Subsequent removal of endothelium produced no further change in response. This implies that the action of extraluminal oxyHb is to eliminate any endothelium-dependent responses. If cerebral vasospasm after subarachnoid hemorrhage is initiated by hemoglobin released from the clot surrounding the artery, at least one component of its action appears to involve interference with endothelial function.

Acetylcholine↗
PubMed1981

Effect of sulfation of CCK-8 on its stimulation of the endocrine and exocrine secretion from the isolated perfused porcine pancreas.

The secretory effect of sulfated and nonsulfated cholecystokinin octapeptide (CCK-8) was studied on the isolated perfused porcine pancreas. Both CCKs in concentrations from 10(-11) to 10(-8) mol/l in the presence of glucose (7.5, 5.0 or 3.5 mmol/l) were without effect on insulin and glucagon release. The exocrine secretion was stimulated by both CCKs in a dose-dependent manner, but sulfated CCK-8 was considerably more potent. The study shows that CCK-8, a major constituent of endogenous CCK, does not contribute to the incretin mechanism, irrespective of degree of sulfation. In contrast, CCK-8 is a potent stimulator of exocrine pancreatic secretion. For this effect sulfation is crucial.

Animals↗
PubMed1978

Very low density lipoprotein. Metabolism of phospholipids, cholesterol, and apolipoprotein C in the isolated perfused rat heart.

The fate of rat plasma very low density lipoprotein (VLDL) constituents was determined in the isolated perfused rat heart. VLDL was labeled with [(14)C]palmitate, (32)P-phospholipids, [(3)H] cholesterol, and (125)I-apolipoprotein C (apoC). Perfusions were performed with an albumin-containing buffer and without plasma. Radioactivity was followed in fractions of d < 1.019, d 1.019-1.04, d 1.04-1.21, and d > 1.21 g/ml, prepared by ultracentrifugation.VLDL triglycerides were progressively hydrolyzed to fatty acids (10-120-min perfusions). Concomitantly, phospholipids, cholesterol (predominantly unesterified), and apoC were removed from the VLDL to all other fractions. About 30-35% of the phosphatidylcholine was hydrolized to lysophosphatidylcholine and was recovered at d > 1.21 g/ml. The phosphatidylcholine-and triglyceride-hydrolyzing activities were confined to membrane supported enzyme(s). The other 60-65% of the phosphatidylcholine was removed unhydrolyzed and was found in fractions of d 1.019-1.04 (10-15%), d 1.04-1.21 (25-30%), and d > 1.21 g/ml (15-20%). [(32)P]Sphingomyelin accumulated at the fraction of d 1.04-1.21 g/ml. Unesterified cholesterol was found in the fraction of d 1.04-1.21 g/ml. ApoC was recovered predominantly in fractions of d 1.04-1.21 (50-60%) and d > 1.21 g/ml (30-40%). Cholesteryl esters were associated with VLDL during the hydrolysis of 50-70% of the triglycerides, but with advanced lipolysis, appeared in higher densities, mainly d 1.019-1.04 g/ml. The fraction of d 1.04-1.21 g/ml, (containing phosphatidylcholine, sphingomyelin, unesterified cholesterol, and apoC) contained by negative staining, many disk-like structures. The study demonstrated that removal of surface constituents (phospholipids, unesterified cholesterol, and apoC) during lipolysis of VLDL is an intrinsic feature of the lipolytic process, and is independent of the presence of plasma. It also indicated that surface constituents may be removed in a particulated form.

Animals↗
PubMed1985

Parathyroid hormone enhances glucagon secretion from the isolated perfused rat pancreas preparation.

We examined whether PTH could increase glucagon secretion in an in vitro system, the isolated perfused rat pancreas. Since the response of the A cell has been shown to be modulated by antecedent exposure to elevated concentrations of glucose, bovine PTH (Beckman 1-34) was superimposed upon 15-min infusions of glucose followed by arginine or upon infusions of arginine alone. In the presence of PTH (44 ng/ml) and when the ambient calcium concentration was 9.0 mg/dl, arginine (168 mg/dl)-induced glucagon secretion was augmented. This occurred regardless of whether arginine was preceded by glucose (150 mg/dl). The glucagonotropic effect of PTH was absent in the presence of a low ambient calcium concentration (3.0 mg/dl). PTH failed to affect glucose-induced glucagon suppression.

Animals↗
PubMed1986

Calcitonin gene-related peptide stimulates somatostatin release from isolated perfused rat stomach.

Effect of calcitonin gene-related peptide (CGRP) on somatostatin release was investigated on the isolated perfused rat stomach. Perfusion with CGRP (0.1 nM-100 nM) caused a significant and dose-dependent increase in effluent somatostatin levels. The somatostatin response to CGRP was rapid in onset and reversible immediately after the cessation of CGRP infusion. These findings suggest that CGRP stimulates the release of gastric somatostatin, thereby modulating gastric functions in rat.

Animals↗
PubMed2000

Effects of neuropeptide Y on double-peaked constrictor responses to periarterial nerve stimulation in isolated, perfused canine splenic arteries.

The periarterial electrical nerve stimulation readily induced a double-peaked vasoconstriction in the isolated, perfused canine splenic artery. P2X-Purinoceptors have previously been shown to be involved mainly in the 1st-phase response and alpha 1-adrenoceptors, mostly in the 2nd-one. The dose used of neuropeptide Y (NPY) (0.01-0.1 microM) given into the preparation caused a slight but insignificant vasoconstriction. The treatment with NPY at concentrations of 0.01-0.1 microM produced a parallel inhibition on the 1st- and 2nd-phase responses following nerve stimulation at the frequencies used (1-10 Hz) in a dose-dependent manner. The vasoconstrictor responses to administered ATP (0.01-1 mumol) or noradrenaline (0.03-3 nmol) were slightly but not significantly potentiated by 0.1 microM NPY. The results indicate that NPY predominantly exerts a prejunctionally inhibitory modulation on the purinergic and adrenergic transmission in peripheral sympathetic nerves innervating the canine splenic artery.

Adenosine Triphosphate↗
PubMed1991

The effect of sodium iothalamate on the vascular resistance of the isolated perfused rat kidney.

The direct effects of sodium iothalamate on renal vascular resistance (RVR) were examined using the isolated perfused rat kidney experimental model. A concentration-dependent biphasic change in RVR was produced with the hyperosmolar solution of sodium iothalamate [(Conray 420), 420 mgI/ml, 2500 mOsmol/kg/H2O]. The response characterized by an initial fall followed by a prolonged increase in RVR on discontinuation of the iothalamate infusion. No significant change in RVR was observed when iothalamate was infused as an iso-osmotic solution (60 mgI/ml, 280 mOsmol/kg/H2O) at a rate of 0.525 ml/min. to produce a concentration of 4.2 mgI/ml in the renal perfusate. We conclude that sodium iothalamate can exert direct biphasic effects on RVR which are mediated by its hyperosmolality rather than its chemical content.

Animals↗
PubMed2004

The isolated perfused rat kidney model: a useful tool for drug discovery and development.

Over the past three decades, the Isolated Perfused Rat Kidney (IPK) has been used to study numerous aspects of renal drug disposition. Among the available ex-vivo methods to study renal transport, the IPK allows for elucidation of the overall contributions of renal transport mechanisms on drug excretion. Therefore, IPK studies can provide a bridge between in vitro findings and in vivo disposition. This review paper begins with a detailed overview of IPK methodology (system components, surgical procedure, study design). Various applications of the IPK are then presented. These applications include characterizing renal excretion mechanisms, screening for clinically significant drug interactions, studying renal drug metabolism, and correlating renal drug disposition with drug-induced changes in kidney function. Lastly, the role of IPK studies in drug development is discussed. Demonstrated correlations between IPK data and clinical outcomes make the IPK model a potentially useful tool for drug discovery and evaluation.

Algorithms↗
PubMed1980

A different action of hypothermia on insulin release from the isolated, perfused rat pancreas, depending on the stimulating agent.

Two series of experiments were performed in parallel on the isolated perfused rat pancreas. The experimental conditions differed only as pertaining to temperature. In one series the organ and the perfusion liquid were maintained at 37.5 degrees C and in the other at 28 degrees C. The pancreases were perfused from the start of the experiments with a perfusion medium containing 8.3 mmol/l glucose. The effects of various stimulatory agents were studied (glucose 16.6 mmol/l, tolbutamide 0.4 mmol/l, acetylcholine 0.5 micromole/l, glucagon, 2.8 nmol/l, and L-isoprenaline 0.05 micromole/l). At 37.5 degrees C the insulin secretion induced by high glucose or tolbutamide, acetylcholine, and glucagon was biphasic and not statistically different. In all cases the hypothermia (28 degrees C) decreased insulin secretion. However, glucose-induced and tolbutamide-induced insulin secretion was more decreased than the secretion induced by acetylcholine and glucagon. The study of the secretion ratios obtained at 28 degrees C relative to 37.5 degrees C showed that the ratios for the glucose and tolbutamide groups were significantly lower than those obtained for acetylcholine and glucagon groups for both the first and the second phase. The ratios were not significantly different between glucose and tolbutamide on the one hand and acetylcholine and glucagon on the other hand. In all groups the ratios 28 degrees/37.5 degrees for the second phase were lower than those obtained during the first phase. L-isoprenaline induced only a weak increase in insulin secretion and this was not long lasting; this increase was not statistically different at both temperatures.

Acetylcholine↗
PubMed1981

Glucose and cyclic AMP as stimulators of somatostatin and insulin secretion from the isolated, perfused rat pancreas: a quantitative study.

The secretory responses of beta and delta cells were compared in the isolated, perfused, rat pancreas. Insulin release was stimulated 50-fold and somatostatin (SRIF) secretion twofold when the glucose concentration was increased from 100 mg/dl to 300 mg/dl. When islet cyclic AMP (cAMP) was raised by 3-isobutyl-1-methylxanthine (IBMX), the secretion of SRIF was stimulated in a glucose-dependent manner (300 mg/dl greater than 100 mg/dl greater than 25 mg/dl). As expected, insulin release was also potentiated in a similar fashion. A difference in the glucose dependency of the cAMP effect was seen at 25 mg/dl glucose, where 0.25 mM IBMX enhanced the release of SRIF but not that of insulin. In contrast, at 300 mg/dl glucose, IBMX caused a greater potentiation of insulin release than of SRIF release. The release of insulin, when expressed in absolute terms, was stimulated more markedly than that of SRIF under most conditions tested. However, the expression of total hormone released during 30 min of stimulation as a percentage of tissue hormone content allowed a different interpretation of the results. For example, 2.1% and 1.8% of tissue insulin and SRIF contents, respectively, was released during exposure to 300 mg/dl glucose. Surprisingly, under basal conditions (100 mg/dl glucose), 1.0% of total SRIF content was released during 30 min compared with the release of only 0.04% of insulin.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Disopyramide elimination in the isolated perfused rat liver.

The elimination kinetics of disopyramide, [14C]disopyramide and [2H]disopyramide have been studied in the isolated perfused rat liver. Disappearance of disopyramide from perfusate was dose- and time-dependent over the dose range 0.3-7.5 mg. Although the mechanism underlying these observations is unclear, the data are consistent with the presence of enzyme saturation and product inhibition. Biliary secretion of conjugated metabolites appeared to be the rate-limiting step in the perfusate clearance of total radioactivity. At doses of 0.3 and 7.5 mg the kinetics of [2H]disopyramide showed a small isotope effect probably of negligible importance.

Animals↗
PubMedDate not supplied

The disposition of valpromide in rats and the isolated perfused rat liver.

The pharmacokinetics and metabolism of valpromide (VPD) were investigated in intact rats and in the isolated perfused rat liver (IPL). The rats and the IPLs were divided into three groups. One was a control (untreated) group. The second consisted of intact rats and IPLs obtained from rats pretreated with phenobarbital. A third group of rats received VPD by oral administration. VPD was partially hydrolyzed to valproic acid (VPA) by the IPL following iv administration to intact rats. The fraction of the total body clearance of VPD which furnished VPA as a metabolite (fm) in the rats was 63%. The rate and extent of this conversion were greater in the phenobarbital-pretreated rats and in the IPLs than in the control group. Our studies showed that phenobarbital can induce the hydrolytic biotransformation of VPD to VPA. This is in addition to its known effect on oxidative metabolic pathways. In rats, as in humans and dogs, VPD is biotransformed to VPA in the liver. The complete oral bioavailability of VPD and the fact that the AUC of VPA obtained after oral administration of VPD was not higher than that obtained after the iv injection of VPD indicates that the gastrointestinal tract is not one of the metabolic sites of VPD to VPA conversion.

Administration, Oral↗