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 1,369 records · Page 76Linked to original sources
PubMed1992

[Effects of carteolol on electroretinograms in isolated perfused cat eye].

Effects of carteolol on ERG b-wave amplitude were investigated in dark adapted isolated perfused cat eyes. Carteolol enhanced ERG b-waves with both strong stimuli that reflect the function of both the rod and cone systems, and weak stimuli that reflect the function of the rod system. These observations suggest the following two ideas i.e.: 1. Carteolol increases the flow in retinal vessels of perfusate. or 2. Carteolol has interaction with retinal beta-adrenergic receptors related to the origin of the ERG b-wave. It is likely that both participate in the intrinsic sympathomimetic activity and the release activity of the endothelium derived relaxing factor of carteolol.

Animals↗
PubMedDate not supplied

Disposition of carbamazepine and its 10,11-epoxide metabolite in the isolated perfused rat liver.

The disposition of carbamazepine and its metabolite, the 10,11-epoxide, was investigated in isolated perfused livers from control and phenobarbital-pretreated rats. The mean hepatic clearance of carbamazepine was 0.28 ml per min per g of liver corresponding to a mean extraction ratio of 0.16 and a mean intrinsic clearance of 0.33 ml per min g of liver. In phenobarbital-pretreated rats, there was an approximately 40% increase in the hepatic clearance due to a concomitant increase in the mean extraction ratio from 0.16 to 0.26. The carbamazepine-10,11-epoxide generated in the liver approached and attained its peak concentration more rapidly in pretreated than in control rat livers. In the latter group there was virtually no disappearance of the epoxide from the perfusate, whereas in the pretreated rat livers the perfusate concentrations declined after 90 min. The extremely low clearance of the epoxide generated by metabolism in control rat liver was confirmed by administration of the epoxide per se to the perfusion system. The mean extraction ratio of the epoxide in this situation was only 0.016 and it was unaffected by prior treatment of the rats with phenobarbital. However, the epoxids exhibited dose-dependent kinetics with a 3-fold increase in the extraction ratio when the administered dose was reduced from 500 to 166 microng. The observed induction of the hepatic clearance of carbamazepine is supportive of the involvement of this mechanism in the interaction of this drug with various other anticonvulsants in both children and adults.

Animals↗
PubMedDate not supplied

Effects of norepinephrine on hepatic amino acid metabolism in isolated perfused rat liver.

The effects of norepinephrine (NE) on hepatic amino acid exchanges were studied in the isolated perfused rat liver using a recirculating system with a medium containing amino acids at twice physiologic concentrations. Norepinephrine induced a significant decrease (25%) in portal blood flow at a concentration of 2 ng/ml (10(-8) M). The hormone also increased total hepatic amino acid uptake, essentially through a switch from glutamine release to net uptake. There was no modification in free intracellular amino acids, but glycogen was slightly decreased, and glucose production was increased. Taken as a whole, these results suggest that NE modulates hepatic protein balance.

Amino Acids↗
PubMedDate not supplied

Vascular relaxation by ifenprodil in the isolated perfused rat mesenteric artery.

The possible mechanism of vascular relaxation by ifenprodil has been examined in the isolated perfused rat mesenteric artery preparation. Ifenprodil (5.0 X 10(-9)-5.0 X 10(-8) M) noncompetitively blocked noradrenaline- and cirazoline-induced vasoconstrictor responses. This concentration range did not affect responses to 5-hydroxytryptamine and potassium chloride. However, in concentrations above 10(-6) M, ifenprodil caused (a) reversal of constrictor responses to excess potassium given either by bolus injections (3.4 X 10(-2)-5.4 X 10(-1) M) or by continuous perfusion (55 mM) and (b) inhibition of Ca2+-induced constrictor effects in arteries perfused with Ca2+-free depolarizing Krebs solution. It is concluded that ifenprodil blocks Ca2+ mobilization through both the ion channels coupled to alpha-adrenoceptors and the potential-sensitive channels.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Renal clearance of carprofen in the isolated perfused rat kidney.

The renal clearance of the anti-inflammatory agent, carprofen, was studied in the isolated perfused rat kidney (IPK). The dosing range used (0.5-25 mg) produced perfusate concentrations comparable to and greater than therapeutic plasma concentrations expected in man. In vitro studies in the rat were done as a basis for comparison to the in vitro IPK parameters. Because of its extensive binding (greater than 99%) to the protein fraction of the perfusate, the urinary excretion of carprofen was low an perfusate concentration-dependent. The calculation of the tubular transit rate at each carprofen concentration indicated the following net mechanism(s) of renal carprofen clearance: filtration at low concentration, reabsorption at intermediate concentrations, and secretion at the highest concentration. At low urinary pH and flow rates, reabsorption effectively counteracted secretion. The present in vitro studies suggest that carprofen is excreted by the kidney by the pathway common to a variety of organic acids.

Animals↗
PubMed1982

Lipogenesis from ketone bodies in the isolated perfused rat liver. Evidence for the cytosolic activation of acetoacetate.

The production of ketone bodies by the isolated perfused rat liver has been measured by the dilution of the specific activity of tracer amounts of beta-hydroxy[3-14C]butyrate and by accumulation in the perfusate. The latter method has been found to underestimate ketogenesis by 12 to 44% because it does not take into account acetoacetate utilization by the liver. Incorporation of ketone bodies into fatty acids and 3-beta-hydroxysterols was compared to total lipid synthesis measured by incorporation of tritium from tritiated water. A preferential labeling of 3-beta-hydroxysterols over fatty acids was observed, which is consistent with the activation of acetoacetate in the cytosol by acetoacetyl-CoA synthetase. Ketone bodies contribute 19 to 80% of the carbon incorporated into sterols and up to 22% of the carbon incorporated into fatty acids, depending upon the metabolic status of the liver. The activity of acetoacetyl-CoA synthetase is more than sufficient to account for the rate of ketone body utilization. Conditions that decrease the citrate cleavage pathway of acetyl group translocation through the mitochondrial membrane are associated with an increase in carbon flux through acetoacetyl-CoA synthetase. Formation of acetoacetate in the mitochondria and its utilization in the cytosol thus appear to be a secondary pathway of acetyl group translocation operating concurrently with the predominant citrate cleavage pathway.

Acetoacetates↗
PubMed1980

Absence of effect of diazoxide on sodium and water handling in the isolated perfused rat kidney.

The effect of the thiazide derivative diazoxide on water and sodium handling of the isolated perfused rat kidney was studied. In kidneys of normotensive rats no influence on diuresis, glomerular filtration rate or sodium and potassium excretion rates could be detected whereas hydrochlorothiazide showed the anticipated effects. The diuretic effect of the latter compound was not inhibited nor potentiated by pretreatment with diazoxide. In kidneys of hypertensive rats, studied at different ages: 10, 20, 30, and 45 weeks respectively, no acute effects of diazoxide on tubular function were found either. Diazoxide and hydrochlorothiazide both resulted into a small drop of renal perfusion pressure indicating that renal vascular resistance was lowered. The results suggest that the water and sodium retention frequently observed in patients treated with diazoxide are not caused by a direct effect of the drug on tubular function but are mediated by its peripheral and/or intrarenal vascular effects.

Animals↗
PubMed1995

[Effect of halothane on the energy metabolism of isolated perfused rat kidney as analysed by 31P-NMR].

The effects of halothane on energy metabolism of isolated perfused rat kidney were studied by 31P-NMR spectroscopy. Rat kidney was perfused by physiological medium containing halothane. Perfusion was carried out continuously in addition to ischemic period of 30 or 10 minutes. In continuous perfusion study, halothane concentration below 4% did not affect renal ATP level but halothane above 6% decreased ATP level significantly. In ischemic study, changes of renal energy metabolism were not influenced by halothane below 4% throughout the experiment, but halothane above 6% decreased ATP levels significantly after reperfusion. From the viewpoint of energy metabolism, it can be said that a low concentration of halothane does not damage renal cells but a high concentration of halothane has possibility to damage them. During and after ischemic insult, halothane does not diminish renal damage, but on the contrary a high concentration of halothane reversely worsens it.

Adenosine Triphosphate↗
PubMedDate not supplied

The isolated perfused liver. a new model using autologous blood and porcine slaughterhouse organs.

INTRODUCTION: Current models of isolated and perfused livers are limited by nonphysiologic perfusates or the need for the use of high numbers of laboratory animals. The present study was performed in order to rectify these difficulties. METHODS: To establish a new isolated perfused liver model, a perfusion circuit was developed using normothermic, autologous hemoperfusion and organs obtained from a slaughterhouse. RESULTS: Stable organ function was maintained over 220 min. The organs displayed physiologic values for measured variables, including oxygen consumption which varied from 5.2+/-1.5 ml/min at 40 min to 5.2+/-2.4 ml/min at 220 min, and bile production (0.15-0.31 ml/min, respectively). DISCUSSION: The present studies demonstrate a new approach for experimental liver perfusion by combining the optimal perfusion medium of autologous blood and slaughterhouse organs as source material.

Alanine Transaminase↗
PubMed1998

Cardiac effects of angiotensin I and angiotensin II: dose-response studies in the isolated perfused rat heart.

We investigated the effects of angiotensin I (4 x 10(-9), 4 x 10(-8) and 4 x 10(-7) M) on myocardial contractility, heart rate and coronary perfusion in the isolated rat heart before and after inhibition of angiotensin-converting enzyme (ACE) by captopril (4 x 10(-4) M). We also studied the post-ischaemic recovery of cardiac function in isolated hearts subjected to global myocardial ischaemia and reperfused with various doses of angiotensin II (1 x 10(-9), 1 x 10(-8) and 1 x 10(-7) M). Angiotensin I significantly reduced coronary flow, the vasoconstrictor effect of a second identical dose was attenuated after inhibition of ACE with captopril. Angiotensin II reduced coronary flow to the same extent as angiotensin I at a concentration four times lower. Left ventricular developed pressure was reduced by angiotensin I and angiotensin II in a dose-dependent manner. Heart rate was not affected by angiotensin I and was significantly lowered by the highest doses (1 x 10(-8) and 1 x 10(-7) M) of angiotensin II. Post-ischaemic recoveries of vascular and contractile function were similar in control hearts and in hearts given angiotensin II during reperfusion. However, left ventricular end-diastolic pressure was increased by the highest dose (1 x 10(-7) M) of angiotensin II throughout reperfusion compared with controls or hearts receiving lower doses (NS). In conclusion the attenuated vasoconstrictor response to angiotensin I after captopril pre-treatment confirms the existence of an intracardiac renin-angiotensin system operative in vitro. Our results also suggest that angiotensin II, at a high concentration, may play a negative role in relaxation in the ischaemic-reperfused injured heart.

Angiotensin I↗
PubMed1988

Electrophysiological study of transport systems in isolated perfused pancreatic ducts: properties of the basolateral membrane.

In order to study the mechanism of pancreatic HCO3- transport, a perfused preparation of isolated intra- and interlobular ducts (i.d. 20-40 microns) of rat pancreas was developed. Responses of the epithelium to changes in the bath ionic concentration and to addition of transport inhibitors was monitored by electrophysiological techniques. In this report some properties of the basolateral membrane of pancreatic duct cells are described. The transepithelial potential difference (PDte) in ducts bathed in HCO3(-)-free and HCO3(-)-containing solution was -0.8 and -2.6 mV, respectively. The equivalent short circuit current (Isc) under similar conditions was 26 and 50 microA . cm-2. The specific transepithelial resistance (Rte) was 88 omega cm2. In control solutions the PD across the basolateral membrane (PDbl) was -63 +/- 1 mV (n = 314). Ouabain (3 mmol/l) depolarized PDbl by 4.8 +/- 1.1 mV (n = 6) within less than 10 s. When the bath K+ concentration was increased from 5 to 20 mmol/l, PDbl depolarized by 15.9 +/- 0.9 mV (n = 50). The same K+ concentration step had no effect on PDbl if the ducts were exposed to Ba2+, a K+ channel blocker. Application of Ba2+ (1 mmol/l) alone depolarized PDbl by 26.4 +/- 1.4 mV (n = 19), while another K+ channel blocker TEA+ (50 mmol/l) depolarized PDbl only by 7.7 +/- 2.0 mV (n = 9). Addition of amiloride (1 mmol/l) to the bath caused 3-4 mV depolarization of PDbl. Furosemide (0.1 mmol/l) and SITS (0.1 mmol/l) had no effect on PDbl. An increase in the bath HCO3- concentration from 0 to 25 mmol/l produced fast and sustained depolarization of PDbl by 8.5 +/- 1.0 mV (n = 149). It was investigated whether the effect of HCO3- was due to a Na+-dependent transport mechanism on the basolateral membrane, where the ion complex transferred into the cell would be positively charged, or whether it was due to decreased K+ conductance caused by lowered intracellular pH. Experiments showed that the HCO3- effect was present even when the bath Na+ concentration was reduced to a nominal value of 0 mmol/l. Similarly, the HCO3- effect remained unchanged after Ba2+ (5 mmol/l) was added to the bath. The results indicate that on the basolateral membrane of duct cells there is a ouabain sensitive (Na+ + K+)-ATPase, a Ba2+ sensitive K+ conductance and an amiloride sensitive Na+/H+ antiport. The HCO3- effect on PDbl is most likely due to rheogenic anion exit across the luminal membrane.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1981

Influence of uranyl nitrate upon tubular reabsorption and glomerular filtration in blood perfused isolated dog kidneys.

The early changes in tubular reabsorption, glomerular filtration, blood flow and sodium excretion brought about by uranyl nitrate were investigated in isolated, blood-perfused dog kidneys during water diuresis. No significant changes in urine volume were observed; the decrease in fluid reabsorption was counterbalanced quantitatively by a reduction in glomerular filtration rate; only a small diminution of renal blood flow was found. The balance between reabsorption and filtration was observed as well when angiotensin action or prostaglandin synthesis were inhibited. The intrarenal venous pressure rose, suggesting that an increase in proximal intratubular hydrostatic pressure caused the decrease in filtration. Tubular back-leak of fluid, or back-diffusion, induced by the toxin, were excluded. The presence of natriuretic compounds in the urine was confirmed.

Absorption↗
PubMed1982

H+ ion secretion in proximal tubule of low-Co2/HCO-3 perfused isolated rat kidney.

Acidification in proximal tubule of the isolated rat kidney, perfused in vitro, was studied by stopped-flow microperfusion techniques, using Sb microelectrodes to measure luminal pH. The kidney was perfused with mammalian Ringer's solution at pH 7.4 buffered by 20 mmol/l phosphate and containing 7.5 g/100 ml bovine albumin, equilibrated with air. Final urine pH was 6.88 +/- 0.5. Steady-state pH in proximal segments was 6.81 +/- 0.03 (n = 80), and acidification half-time (t/2) 7.25 +/- 0.33 (80) s, giving a net secretory H+ ion flux of 0.51 +/- 0.05 nmol . cm-2 . s-1. This flux was about 70% of "in vivo" (blood perfused kidneys). During luminal perfusion with solutions at pH 6.2, back-flux of H+ was 0.82 +/- 0.08 nmol . cm-2 . s-1, with an alkalinization t/2 of 6.33 +/- 0.34 (34) s. The difference between acidification and alkalization t/2 was not significant. This is compatible with a pump-leak system of H+ transport. This is compatible with a pump-leak system of H+ transport. The back flux of H from the lumen was markedly reduced in low Na+ perfused kidneys in the presence of 10(-4) mol/l amiloride in the lumen, indicating that this process is mediated by the luminal Na/H exchanger. Observations in the presence of high K levels suggest that it may have also a charged component. 10(-4) mol/l acetazolamide added to the kidney perfusate reduced acidification to 0.5% of control, and 10(-6) mol/l SITS to 25% of control. Thus, despite the low pCO2 (0.1-0.4 kPa, or 1-3 mm Hg), the CO2/HCO-3 buffer system still plays an important role in tubular acidification in this preparation.

Animals↗
PubMed1976

Cellular metabolite distribution and the control of gluconeogenesis in the perfused isolated rat liver.

Glucose production was measured in isolated rat livers perfused with 100 ml of blood-free recirculating medium. The gluconeogenic rate using L-alanine as substrate was only 55% of that obtained with L-lactate. The steady-state concentration of gluconeogenic and tricarboxylic acid cycle intermediates were measured in freeze clamped biopsies. Livers perfused with L-lactate displayed higher concentrations of malate, alpha-glycerophosphate and beta-hydroxybutyrate probably as a result of a higher state of reduction of the nicotinamide system. Hexose-phosphate intermediates were also increased when L-lactate was the substrate. Phosphoenolpyruvate and 3-phosphoglycerate were considerably elevated when L-alanine was the glucose precursor. Livers perfused with L-lactate displayed higher cytosolic concentration of all the tricarboxylic acid cycle intermediates except oxaloacetate while glutamate was slightly and aspartate considerably higher when alanine was the substrate. In the mitochondrial compartment the pattern of distribution tended to be the opposite; that is, livers perfused with L-lactate showed lower concentrations of all the intermediates except alpha-ketoglutarate. The mitochondrial: cytosolic metabolite gradients of all the intermediates whose distribution was studied were higher in livers perfused with L-alanine. The relevance of these findings to the observed differences in the gluconeogenic fluxes are discussed.

Alanine↗
PubMed1986

The fluosol-perfused isolated canine pancreas: a model for the study of blood component effects in acute pancreatitis.

UNLABELLED: Blood components have been implicated as factors which modulate organ injury in acute pancreatitis. To isolate these effects we compared a standardized isolated, blood-perfused, canine pancreas model as described by Herman-Taylor and modified by Cameron with a model using fluosol, a fluorocarbon, as the perfusate. Pancreatitis was induced using partial pancreatic duct obstruction with secretin induced hypersecretion. Twenty-four dogs were randomized into four groups; (1) blood-perfused control (BPC), (2) fluosol-perfused control (FPC), (3) blood-perfused injury (BPI), (4) fluosol-perfused injury (FPI). All glands were observed for 4 h for mean arterial pressure (MAP), weight gain, gross appearance, and venous amylase. Stability was monitored with blood gases and glucose. Specimens were taken at 4 h for light and electron microscopy. RESULTS: BPI preps had a significantly higher vascular resistance at 3 and 4 h compared to FPI preps (3.85 vs 3.26 PRU and 4.8 vs 3.9 PRU, respectively) (P less than 0.002). Edema formation (3+ vs 1+) and venous amylase (18,543 vs 1961) (P less than 0.001) were greater in BPI than FPI preps. Light and electron microscopy confirmed injury but could not quantify it between injury groups. SUMMARY: Hypersecretion and partial ductal obstruction causes a more severe injury in the blood than the fluosol perfused preparation. Changes in the peripheral resistance seen in the blood perfused model lend support to the theory that the primary injury in this model is at the capillary level and is modulated by a blood component.

Amylases↗
PubMed1976

Regulation of the pyruvate dehydrogenase activity in the isolated perfused heart of guinea-pigs.

The activity and the interconversion of the between the pyruvate after pyruvate should read: utilization in the perfused hearts and the pyruvate dehydrogenease complex has been measured in the isolated perfused working hearts of guinea-pigs. 1. The pyruvate dehydrogenase complex is transferred into the active form by high work, in anoxia, with 2,4-dinitrophenol and by perfusion without substrate. The rate of interconversion is faster in the perfused heart than in the homogenate. 2. The active form of the pyruvate dehydrogenase complex limits the pyruvate oxidation. There is a close correlation between the pyruvate utilization in the perfused hearts and the pyruvate dehydrogenase of the active form in the homogenates of the same hearts. 3. The "adenylate energy charge" of the cells is considered as the main regulating factor of the interconversion of the pyruvate dehydrogenase complex as seen in experiments with anoxia, dinitrophenol and high work. The inactivation of the pyruvate dehydrogenase complex by acetyl CoA can be overcome by decreasing ATP/ADP ratios.

Acetates↗
PubMed1990

The effect of zinc on reperfusion arrhythmias in the isolated perfused rat heart.

Considerable evidence suggests that free radicals engendered by redox-active metals, particularly iron and copper, are causative agents in reperfusion injury following ischemia. This study demonstrates that perfusion of the isolated rat heart with a buffer containing zinc, a non-redox active metal similar to copper in its coordination chemistry, inhibits the development of ventricular arrhythmias during reperfusion. Zinc was employed as the bishistidine complex, Zn--His2, to maintain solubility and permeability. Zn--His2 exerted an antiarrhythmic activity as hearts spent a longer time in normal sinus rhythm and a shorter time in ventricular fibrillation during reperfusion following 10 min of regional ischemia. However, Zn--His2 also produced a negative inotropic and chronotropic effect, evident during equilibration and ischemia. In the course of experiments which began in Israel and continued in the U.S. it was necessary to use two different sources of rats. Hearts from the two sources manifested different sensitivities to the concentrations of Zn--His2, although their physiological effects were similar. Differential activity responses were noted for antiarrhythmic activity, negative inotropic and chronotropic properties, and toxicity. In both groups of untreated hearts the incidence of ventricular fibrillation after ischemia was 100%. Ventricular fibrillation was reduced to 17% at 37.5 microM Zn--His2 in the U.S.-bred rat hearts and to 9% at 200 microM Zn--His2 in those from Israel. These changes in Zn--His2 treated animals were accompanied by a decrease in lactate dehydrogenase release from the myocardium during reperfusion. None of the protective effects was due to histidine alone. These results indicate that zinc prevents ventricular arrhythmias during reperfusion following regional ischemia and may prevent membrane damage, possibly, by reduction of free radical formation.

Animals↗
PubMedDate not supplied

Ultrastructural alterations during the critical phase of reperfusion: a stereological study in buffer-perfused isolated rat hearts.

The present study focuses on myocardial ultrastructural alterations during the early phase of reperfusion. Isolated buffer-perfused rat hearts were exposed to standard perfusion (control group,n = 10); 60 min of global ischemia (n = 10); 60 min of global ischemia followed by 2 min of reperfusion (n = 10); or 60 min of global ischemia followed by 10 min of reperfusion (n = 10). The hearts were perfusion-fixed for electron microscopy, and ultrastructural evaluation was performed using stereological technique in order to obtain an estimate of the volume fraction and absolute volume of different tissue components. EFFECT OF ISCHEMIA: Neither the ventricular nor the myocytic volume differed significantly from the respective control values. Both the myocytic mitochondrial volume (135+/-8 vs control 89+/-6 microl) and the volume of myocytic clear space (35+/-6 vs control 10+/-2 microl) were significantly increased. The capillary volume (22+/-4 vs control 58+/-6 microl) and the volume of the capillary lumen (15+/-3 vs control 48+/-5 microl) were significantly decreased. The volume of the capillary wall, however, was not altered after exposure to ischemia (7+/-3 vs control 10+/-1 microl). ADDITIVE EFFECT OF ISCHEMIA AND REPERFUSION: Both the ventricular volume (755+/-28 vs control 600+/-32 microl) and the myocytic volume (396+/-24 vs control 287+/-16 microl) were significantly increased after 10 min of reperfusion. EFFECT OF REPERFUSION: The ischemic-induced myocytic mitochondrial swelling and increase of clear space were not reinforced during reperfusion. Furthermore, the volume of the capillary lumen and the capillary wall did not alter significantly in the groups exposed to reperfusion compared to the ischemic hearts. In conclusion, stereological evaluation did not reveal significant aggravation of ischemic-induced myocardial injury during the early phase of reperfusion.

Actin Cytoskeleton↗