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P Liss

Publications and source records attributed to P Liss.

At least 19 recordsLinked to original sources

Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension.

AIMS/HYPOTHESIS: Augmented formation of reactive oxygen species (ROS) induced by hyperglycaemia has been suggested to contribute to the development of diabetic nephropathy. This study was designed to evaluate the influence of streptozotocin (STZ)-induced diabetes mellitus, as well as the effects of preventing excessive ROS formation by alpha-tocopherol treatment, on regional renal blood flow, oxygen tension and oxygen consumption in anaesthetized Wistar Furth rats. METHODS: Non-diabetic and STZ-diabetic rats were investigated after 4 weeks with or without dietary treatment with the radical scavenger DL-alpha-tocopherol (vitamin E, 5%). A laser-Doppler technique was used to measure regional renal blood flow, whilst oxygen tension and consumption were measured using Clark-type microelectrodes. RESULTS: Renal oxygen tension, but not renal blood flow, was lower throughout the renal parenchyma of diabetic rats when compared to non-diabetic control rats. The decrease in oxygen tension was most pronounced in the renal medulla. Renal cellular oxygen consumption was markedly increased in diabetic rats, predominantly in the medullary region. Diabetes increased lipid peroxidation and protein carbonylation in the renal medulla. Treatment with alpha-tocopherol throughout the course of diabetes prevented diabetes-induced disturbances in oxidative stress, oxygen tension and consumption. The diabetic animals had a renal hypertrophy and a glomerular hyperfiltration, which were unaffected by alpha-tocopherol treatment. CONCLUSIONS/INTERPRETATION: We conclude that oxidative stress occurs in kidneys of diabetic rats predominantly in the medullary region and relates to augmented oxygen consumption and impaired oxygen tension in the tissue.

Animals↗

Altered response in renal blood flow and oxygen tension to contrast media in diabetic rats.

PURPOSE: To investigate the effect of the contrast medium (CM) iopromide on renal microcirculation and oxygen tension in non-diabetic control and streptozotocin-diabetic Wistar Furth rats. MATERIALS AND METHODS: Oxygen tension was measured with Clark-type microelectrodes and blood flow with laser-Doppler flow probes. In order to differentiate between an acutely increased blood glucose concentration and a long-term diabetic state, some of the non-diabetic control rats were intravenously infused with glucose. RESULTS: CM decreased the medullary oxygen tension in control (non-diabetic normoglycemic) rats ( approximately 35%) but not in diabetic rats. Medullary blood flow in control rats increased after CM administration and remained elevated, while it was unchanged in the diabetic rats. In response to CM, glucose-infused control rats responded similarly to control animals in medullary oxygen tension, but similarly to diabetic rats in medullary blood flow. Contrary to in control rats, medullary oxygen tension was unchanged in diabetic animals after CM administration. CONCLUSION: Streptozotocin-diabetic rats have an altered response to intravenous injection of the CM iopromide compared to non-diabetic rats. The unaltered medullary oxygen tension, seen in the diabetic group after injection of CM, suggests that non-hemodynamic mechanisms are responsible for the increased frequency of renal failure commonly seen among diabetic patients.

Animals↗

Et-A receptor antagonist BQ123 prevents radiocontrast media-induced renal medullary hypoxia.

PURPOSE: Renal vasoconstriction with resultant tissue hypoxia, especially in the renal medulla, has been suggested to play a role in contrast media (CM)-induced nephropathy. Endothelin (ET) is released into the blood stream following CM injection and has been proposed as a potential mediator through its vasoconstrictive properties. MATERIAL AND METHODS: To investigate the possible protective influence of ET-receptor antagonists against CM-induced reduction in renal function, we studied the effects of injection of iopromide with and without pretreatment with BQ123 (ET-A antagonist) or BQ788 (ET-B antagonist) on renal superficial cortical flow (CBF), outer medullary blood flow (OMBF) and outer medullary oxygen tension (pO2) in normal rats. RESULTS: Administration of CM (1600 mg I/kg b.w.) did not affect CBF in any of the groups. However, a transient decrease in OMBF occurred, which was unaffected by both BQ123 and BQ788. Also a transient decrease in outer medullary pO2 was induced by CM administration. The pO2 reduction was significantly smaller after pretreatment with BQ123, than after injection of CM alone or together with BQ788, and pO2 returned more rapidly to the control level. Neither receptor antagonist had an effect on CM-mediated increases in electrolyte excretion. CONCLUSION: In the normal rat, activation of ET-A receptors is partly involved in the depression of outer medullary pO2 caused by injection of iopromide. However, the decrease in OMBF after iopromide injection is not mediated by ET receptors. The beneficial effects of the ET-A receptor antagonist on CM-induced changes in outer medullary pO2 seem therefore not primarily mediated on the hemodynamic level but may rather involve tubular transport mechanisms.

Animals↗

Changing dopaminergic activity through different pathways: consequences for renal sodium excretion, regional blood flow and oxygen tension in the rat.

Dopamine (DA) is an intrarenal natriuretic hormone involved in sodium homeostasis, but the regulation of renal dopaminergic tonus is unclear. We evaluated different pathways for elevating DA tonus to determine which are important for the ability of the kidney to produce natriuresis and studied the accompanying effects on regional renal blood flow and oxygen tension. Thus, we compared the effects of a catechol-O-methyl transferase (COMT)-inhibitor, an unspecific monoamine oxidase (MAO)-inhibitor, a D1-like receptor agonist and a DA precursor in anaesthetized rats. Sodium excretion increased sixfold after COMT inhibition, eightfold after administration of the D1-like agonist, whereas it was similar to control after MAO inhibition and infusion of DA precursor. Urinary dopamine excretion increased 42% by COMT inhibition, 55% by MAO inhibition and 12-fold after DA precursor, but remained unchanged after infusion of the D1-like agonist. The D1-like receptor agonist led to a 38% increase in the cortical blood flow and a 21% increase in outer medullary blood flow. Regional renal blood flow was unaffected by all other treatments. Cortical and outer medullary oxygen tension was unaffected in all treatment groups. To conclude, the natriuretic and haemodynamic properties of an elevation in DA tonus depends on the route by which the elevation occurred. Systemic administration of a D1-like receptor agonist, results in a natriuretic response which, as opposed to the natriuresis seen after COMT inhibition, coincides with an increase in renal cortical and outer medullary blood flow. Precursor delivery or MAO inhibition did not change neither urinary sodium excretion nor renal blood flow.

3,4-Dihydroxyphenylacetic Acid↗

Markedly decreased oxygen tension in transplanted rat pancreatic islets irrespective of the implantation site.

In this study, we syngeneically transplanted islets to three different implantation sites of diabetic and nondiabetic rats, then 9-12 weeks later we measured the blood perfusion and compared the tissue partial pressure of oxygen (PO2) levels of these transplanted islets to endogenous islets. Modified Clark microelectrodes (outer tip diameter 2-6 microm) were used for the oxygen tension measurements, and islet transplant blood perfusion was recorded by laser-Doppler flowmetry (probe diameter 0.45 mm). The islet graft blood perfusion was similar in all islet grafts, irrespective of the implantation site. In comparison, the three implantation organs (the kidney cortex, liver, and spleen) differed markedly in their blood perfusion. There were no differences in islet graft blood perfusion between diabetic and nondiabetic recipients. Within native pancreatic islets, the mean PO2 was approximately 40 mmHg; however, all transplanted islets had a mean PO2 of approximately 5 mmHg. The oxygen tension of the grafts did not differ among the implantation sites. In diabetic recipients, an even lower PO2 level was recorded in the islet transplants. We conclude that the choice of implantation site seems less important than intrinsic properties of the transplanted islets with regard to the degree of revascularization and concomitant blood perfusion. Furthermore, the mean PO2 level in islets implanted to the kidney, liver, and spleen was markedly decreased at all three implantation sites when compared with native islets, especially in diabetic recipients. These results are suggestive of an insufficient oxygenization of revascularized transplanted islets, irrespective of the implantation site.

Animals↗

Transient glomerular hyperfiltration in the streptozotocin-diabetic Wistar Furth rat.

The glomerular hemodynamic response to streptozotocin (STZ)-induced experimental diabetes differs depending on metabolic control and rat strain used. The present study characterize the glomerular filtration rate (GFR) and other renal parameters, weekly up to eight weeks of diabetes in STZ-diabetic Wistar Furth rats. The STZ-treated rats became diabetic within 24 h after treatment and retained a blood glucose concentration of 20-25 mmol/l throughout the experimental period. The GFR was transiently increased during the first 3-5 weeks after induction of diabetes, but thereafter did not differ from control animals. The renal weight increased by approximately 50% during the first week after induction of diabetes, thereafter no further increase in weight occurred. The urinary flow rate and urinary osmolar excretion were approximately 10 times higher in diabetic animals when compared to non-diabetic animals. Although they remained markedly higher than in non-diabetic animals, both the urinary flow rate and the urinary osmolar excretion peaked after 3 weeks of diabetes and thereafter tended to decrease. The urinary sodium and potassium excretions did not differ between non-diabetic and diabetic animals. We conclude that the transient increase in the GFR seen in the human disease, occurs in Wistar Furth rats, which is in contrast to a majority of other rat strains, where the GFR is persistently increased.

Animals↗

Photoreduction and evolution of mercury from seawater

The photoreduction of mercury (Hg2+ to Hg0) in natural seawater was investigated by means of a radiotracer (203Hg2+) solution exposed to natural and simulated sunlight. Different light regimes (dark, natural daylight, and a solar simulator), and dissolved organic carbon (DOC) levels from commercially available humic acids concentrations, were tested in the laboratory to evaluate the possibility of occurrence of the reaction in the environment. The natural seawater prepared accordingly to each experimental condition was continuously purged of the Hg0 formed, which was then re-oxidised in an acid trap and determined. The use of a solar simulator permitted the test of light intensity and wavelength dependence of the process under investigation. The reaction is dependent on the concentration of DOC in the experimental solution, increasing light intensity and decreasing wavelength. Reduction rates were in the range of 0.04-2.2% h(-1) for the DOC concentrations and light regimes tested. The process might have geochemical implications for the cycling of mercury around the air-sea interface.

Journal Article↗

Chronically decreased oxygen tension in rat pancreatic islets transplanted under the kidney capsule.

BACKGROUND: A factor of potential importance in the failure of islet grafts is poor or inadequate engraftment of the islets in the implantation organ. This study measured the oxygen tension and blood perfusion in 1-, 2-, and 9-month-old islet grafts. METHODS: The partial pressure of oxygen was measured in pancreatic islets transplanted beneath the renal capsule of diabetic and nondiabetic recipient rats with a modified Clark electrode (outer tip diameter 2-6 microm). The size of the graft (250 islets) was by purpose not large enough to cure the diabetic recipients. The oxygen tension in islets within the pancreas was also recorded. Blood perfusion was measured with the laser-Doppler technique. RESULTS: Within native pancreatic islets, the partial pressure of oxygen was approximately 40 mm Hg (n=8). In islets transplanted to nondiabetic animals, the oxygen tension was approximately 6-7 mm Hg 1, 2, and 9 months posttransplantation. No differences could be seen between the different time points after transplantation. In the diabetic recipients, an even more pronounced decrease in graft tissue oxygen tension was recorded. The mean oxygen tension in the superficial renal cortex surrounding the implanted islets was similar in all groups (approximately 15 mm Hg). Intravenous administration of glucose (0.1 gxkg(-1)x min(-1)) did not affect the oxygen tension in any of the investigated tissues. The islet graft blood flow was similar in all groups, measuring approximately 50% of the blood flow in the kidney cortex. CONCLUSION: The oxygen tension in islets implanted beneath the kidney capsule is markedly lower than in native islets up to 9 months after transplantation. Moreover, persistent hyperglycemia in the recipient causes an even further decrease in graft oxygen tension, despite similar blood perfusion. To what extent this may contribute to islet graft failure remains to be determined.

Animals↗

Oscillations in oxygen tension and insulin release of individual pancreatic ob/ob mouse islets.

AIMS/HYPOTHESIS: The role of beta-cell metabolism for generation of oscillatory insulin release was investigated by simultaneous measurements of oxygen tension (pO2) and insulin release from individual islets of Langerhans. METHODS: Individual islets isolated from the ob/ob-mice were perifused. Insulin in the perifusate was measured with a sensitive ELISA and PO2 with a modified Clark-type electrode inserted into the islets. RESULTS: In the presence of 3 mmol/l D-glucose, PO2 was 102 +/- 9 mmHg and oscillatory (0.26 +/- 0.04 oscillations/min). Corresponding insulin measurements showed oscillatory release with similar periodicity (0.25 +/- 0.02 oscillations/min). When the D-glucose concentration was increased to 11 mmol/l, PO2 decreased by 30% to 72 +/- 10 mmHg with maintained frequency of the oscillations. Corresponding insulin secretory rate rose from 5 +/- 2 to 131 +/- 16 pmol x g(-1) x s(-1) leaving the frequency of the insulin pulses unaffected. The magnitude of glucose-induced change in pO2 varied between islets but was positively correlated to the amount of insulin released (r2 = 0.85). When 1 mmol/l tolbutamide was added to the perifusion medium containing 11 mmol/l glucose no change in average oscillatory pO2 was observed despite a doubling in the secretory rate. When 8 mmol/l 3-oxymethyl glucose was added to perifusion medium containing 3 mmol/l D-glucose, neither pO2 nor insulin release of the islets were changed. Temporal analysis of oscillations in pO2 and insulin release revealed that maximum respiration correlated to maximum or close to maximum insulin release. CONCLUSION/INTERPRETATION: The temporal relation between oscillations in pO2 and insulin release supports a role for metabolic oscillations in the generation of pulsatile insulin release.

Animals↗

Use of a modified oxygen microelectrode and laser-Doppler flowmetry to monitor changes in oxygen tension and microcirculation in a flap.

Flap failure is a clinical problem in free tissue transfer, and there is no reliable device for monitoring the tissue. Differentiating between an arterial occlusion and venous congestion is also a problem. A study was undertaken to monitor viability in a pedicled groin flap and to compare two different monitoring methods. The oxygen tension in the flap, measured with a modified Clark-type microelectrode (tip diameter = 3 to 8 microm; 90 percent response within 2.6 +/- 0.5 seconds), was compared with changes in blood flow in the flap, measured with a laser-Doppler probe. In 11 Sprague-Dawley rats, the changes in oxygen tension and blood flow in the pedicled groin flap were studied after clamping and subsequent reperfusion of the artery or vein. After occlusion of the artery to the flap, oxygen tension decreased to a stable value (i.e., the recording level remained unchanged for 30 seconds), from 19.7 +/- 1.8 to 0.3 +/- 0.1 mmHg, after 193 +/-25 seconds; blood flow decreased to a stable value, from 117 +/- 21 to 54 +/- 18 perfusion units, after 26 +/- 6 seconds. Clamping of the vein resulted in a decrease in oxygen tension, from 17.1 +/- 1.8 to 1.4 +/- 0.7 mmHg, after 416 +/- 67 seconds, and blood flow decreased to a stable value, from 90 +/- 14 to 35 +/- 6 perfusion units, after 107 +/- 27 seconds. The results of this study show that there is a difference in oxygen tension and blood flow responses between arterial and venous occlusion and that it may be possible with both methods to distinguish arterial from venous occlusion. However, although oxygen tension measurements are slightly slower in response than laser-Doppler measurements, the values are more reliable as a diagnostic tool for interpretation of a vessel occlusion.

Animals↗

Engraftment and growth of transplanted pancreatic islets.

Transplantation of pancreatic islets may provide a cure for type 1 diabetes. However, this treatment can currently be offered only to very few patients. To improve transplantation success we need to understand better the mechanisms of how the implanted islets survive, grow and/or maintain adequate function. We herein report on our studies to evaluate the factors responsible for the engraftment, i.e. revascularization, reinnervation etc., of transplanted islets and relate these factors to the metabolism and growth of the islets. Graft metabolism can be monitored by microdialysis probes that allow for the measurement of minute amounts of islet metabolites and hormonal products. Growth of the endocrine cells can be stimulated both in vitro before implantation and in vivo post-transplantation. Another problem is rejection of transplanted islets, which may be overcome by the microencapsulation of islets. The knowledge gained by the present studies will enable us to elucidate the optimal treatment of islets to ensure a maximal survival of the transplanted islets, and may be applied also to clinical islet transplantation.

Animals↗

Effect of furosemide or mannitol before injection of a non-ionic contrast medium on intrarenal oxygen tension.

Oxygen tension (pO2) in rat renal cortex and outer medulla was studied after an intravenous injection of mannitol or furosemide, followed 10 minutes later by an intravenous injection of the non-ionic X-ray contrast medium (CM) iopromide (370 mg iodine/ml). Ten minutes after mannitol injection, before injection of CM, pO2 in the medulla had decreased from a control level of 32 +/- 3 to 28 +/- 4 mm Hg. The addition of CM caused a further decrease, to 24 +/- 5 mm Hg, which was a significant reduction. Ten minutes after furosemide injection the pO2 in the medulla had increased significantly, from a control value of 32 +/- 2 to 44 +/- 4 mm Hg. Injection of CM caused a significant decrease in pO2 to 37 +/- 3 mm. Ringer's solution (n = 6) caused no changes. We conclude that pretreatment with mannitol or furosemide does not prevent the CM-induced decrease in pO2 in the outer medulla.

Animals↗

Hypoperfusion in the renal outer medulla after injection of contrast media in rats.

PURPOSE: The effect on regional renal blood was studied after injection of nonionic iso-osmolar iotrolan or ionic high-osmolar iothalamate. MATERIAL AND METHODS: Laser-Doppler flowmetry was used to measure outer medullary (OMBF) and superficial cortical blood flow (CBF) simultaneously in anesthetized rats. Iotrolan (320 mOsm/kg H2O) was injected i.v. at a dose of 600 mg I/kg b.w. (normal dose) over 2 min or 1,600 (high dose) mg I/kg b.w. over 2 or 8 min. Iothalamate (2,580 mOsm/kg H2O) was injected i.v. at a dose of 1,600 (high dose) or 2,900 (extremely high dose) mg I/kg b.w. over 2 min. RESULTS: At the normal dose and 2-min injection of iotrolan, OMBF was reduced by 25+/-9% over 20 min. The high dose of iotrolan injected over 8 min resulted in a reduction in OMBF slightly smaller (17+/-9%) than that induced by the normal dose but lasting longer (30 min). Compared to the normal dose, the high dose and fast (2 min) injection of iotrolan resulted in a greater and more prolonged decrease in OMBF (32+/-6% lasting 50 min). After the high dose of iothalamate (1,600 mg I/kg) there was a decrease in OMBF by 21+/-6%, lasting 30 min. An extremely high dose (2,900 mg I/kg b.w.) gave a heterogeneous response with a mean increase in OMBF of 48+/-24% occurring 60 min after the injection. CONCLUSION: Iso-osmolar and high-osmolar contrast media (CM), at normal and high doses, decrease OMBF, while an extremely high dose of iothalamate may result in an increase. The depression of outer medullary perfusion may have implications for CM-induced acute renal failure in view of the vulnerability of this region to a decrease in oxygen tension.

Animals↗

The haemodynamic effects of iodinated water soluble radiographic contrast media: a review.

All classes of iodinated water-soluble radiographic contrast media (RCM) are vasoactive with the iso-osmolar dimers inducing the least changes in the vascular tone. The mechanisms responsible for RCM-induced changes in the vascular tone are not fully understood and could be multifactorial. A direct effect on the vascular smooth muscle cells causing alterations in the ion exchanges across the cell membrane is thought to be an important factor in RCM-induced vasodilatation. The release of the endogenous vasoactive mediators adenosine and endothelin may also play a crucial role in the haemodynamic effects of RCM particularly in the kidney. In addition, the effects of RCM on blood rheology can cause a reduction in the blood flow in the microcirculation. The purpose of this review is to discuss the pathophysiology of the haemodynamic effects of RCM and to offer some insight into the biology of the endothelium and vascular smooth muscle cells as well as the pharmacology of the important vasoactive mediators endothelin and adenosine.

Adenosine↗

Injection of low and iso-osmolar contrast medium decreases oxygen tension in the renal medulla.

The oxygen tension (PO2) in the renal cortex and outer renal medulla in 26 rats was studied by use of oxygen microelectrodes before and after injection of x-ray contrast media (CM). The CM, iopromide, ioxaglate and iotrolan were administrated intravenously in iodine equivalent doses (1,600 mg iodine/kg body wt). Ringer's solution was used as the control. In the outer medulla, all three CM induced a decrease in PO2: iopromide (N = 6) from 30 +/- 3 to 18 +/- 4 mm Hg; ioxaglate (N = 7) from 32 +/- 6 to 15 +/- 4 mm Hg; and iotrolan (N = 6) from 36 +/- 3 to 14 +/- 4 mm Hg. All these decreases were significant. After the injection of Ringer's (N = 7) there was an increase from 34 +/- 3 to 35 +/- 3 mm Hg. In the cortex a slight decrease was noted for injection of CM, but this was significant only after injection of iotrolan. All tested contrast media decrease PO2 in the outer renal medulla, which may partly explain contrast medium-induced acute renal failure.

Acute Kidney Injury↗