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Samuel N. Heyman - One of the best experts on this subject based on the ideXlab platform.
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Renal Parenchymal Hypoxia, Hypoxia Adaptation, and the Pathogenesis of Radiocontrast Nephropathy
Clinical Journal of The American Society of Nephrology, 2007Co-Authors: Samuel N. Heyman, Seymour Rosen, Christian RosenbergerAbstract:Background and objectives: Renal parenchymal Po2 declines after the administration of iodinated Radiocontrast Agents, reaching critically low levels of approximately 10 mmHg in medullary structures. Design, setting, participants, & measurements: In this review, the causes of renal parenchymal hypoxia and its potential role in the pathogenesis of contrast nephropathy are appraised. Results: Commonly associated predisposing factors are associated with a propensity to enhance renal hypoxia. Indeed, animal models of Radiocontrast nephropathy require the induction of such predisposing factors, mimicking clinical scenarios that lead to contrast nephropathy in high-risk individuals. In these models, in association with medullary hypoxic damage, a transient local cellular hypoxia response is noted, initiated at least in part by hypoxia-inducible factors. Some predisposing conditions that are distinguished by chronically aggravated medullary hypoxia, such as tubulointerstitial disease and diabetes, are characterized by a priori upregulation of hypoxia-inducible factors, which seems to confer tolerance against Radiocontrast-related hypoxic tubular damage. Renal dysfunction under such circumstances likely reflects to some extent altered intrarenal hemodynamics, rather than acute tubular injury. Conclusions: Real-time, noninvasive novel methods may help to differentiate between evolving tubular damage and altered hemodynamics and in the design of appropriate preventive interventions.
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Effect of Radiocontrast Agents on Intrarenal Nitric Oxide (NO) and NO Synthase Activity
Experimental nephrology, 1998Co-Authors: Samuel N. Heyman, Marina Goldfarb, Fanni Carmeli, Ahuva Shina, Daniel Rahmilewitz, Mayer BrezisAbstract:Background/Aims: Contrast media (CM) induce a biphasic renal hemodynamic response, with late prominent cortical vasoconstriction and marked outer medullary vasodilation. The objecti
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Effects of ioversol versus iothalamate on endothelin release and Radiocontrast nephropathy.
Investigative radiology, 1993Co-Authors: Samuel N. Heyman, Mayer Brezis, Seymour Rosen, Barbara A. Clark, Lloyd G. Cantley, Katherine Spokes, Franklin H. EpsteinAbstract:RATIONALE AND OBJECTIVES Certain Radiocontrast Agents, including iothalamate, iohexol, and ioxaglate, release the renal vasoconstrictor peptide endothelin from vascular endothelium in a way that might contribute to Radiocontrast nephropathy. The effects of the nonionic, low osmolar agent, ioversol, on endothelin release and renal function are investigated. METHODS Effects of ioversol were compared with equi-iodine doses of iothalamate when applied to cultured bovine aortic endothelial cells or injected into normal rats and rats preconditioned by uninephrectomy, salt depletion, and indomethacin (USIC) to develop Radiocontrast nephropathy. RESULTS In comparison with iothalamate, ioversol had a greatly reduced propensity to stimulate the release of endothelin, from cultured cells and when injected into anesthetized rats. Ioversol produced less renal vasoconstriction than did iothalamate, in control and in USIC rats, and the development of Radiocontrast nephropathy, assessed by creatinine clearance and morphologic damage to the renal medulla, was largely avoided. CONCLUSIONS These results strengthen the hypothesis that endothelin release induced by Radiocontrast Agents is correlated with their renal toxicity and therefore, may play a role in Radiocontrast nephropathy.
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Radiocontrast Agents induce endothelin release in vivo and in vitro.
Journal of the American Society of Nephrology : JASN, 1992Co-Authors: Samuel N. Heyman, Mayer Brezis, Seymour Rosen, Barbara A. Clark, Katherine Spokes, N. Kaiser, Franklin H. EpsteinAbstract:The intravascular administration of the ionic Radiocontrast agent sodium iothalamate (2.9 g of iodine/kg body wt) to rats induced an increase in plasma concentration of immunoreactive endothelin from 21.3 +/- 1.2 to 36 +/- 3 fmol/mL, preceded by a transient rise in the plasma level of atrial natriuretic peptide and associated with a fall in RBF. Equi-iodine amounts of the nonionic Agents ioxaglate and iohexol elicited similar or more marked changes in plasma endothelin, but hypertonic solutions of NaCl, mannitol, or glucose did not. Comparable levels of endothelin produced by infusions of endothelin-1 induced a reduction of up to 29% in RBF. Iothalamate and iohexol stimulated endothelin release from cultured bovine endothelial cells, suggesting a direct effect of ionic and nonionic Agents on vascular endothelium. The data invite speculation that under some circumstances endothelin release might play a role in the circulatory changes caused by these compounds and in the pathogenesis of Radiocontrast nephropathy.
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Experimental nephrotoxicity of the Radiocontrast Agents iohexol, ioxaglate, and iothalamate. An in vitro and in vivo study.
Investigative radiology, 1991Co-Authors: Mayer Brezis, Greenfeld Z, Herman M, Samuel N. Heyman, Seymour RosenAbstract:The authors compared the renal toxicity of the low osmolality Radiocontrast Agents, iohexol and ioxaglate, and the ionic agent, iothalamate, at equivalent iodine dose, using experimental models in vitro and in vivo. In isolated perfused rat kidneys, all Agents induced comparable biphasic hemodynamic changes, associated with similar declines in glomerular filtration rate (GFR) and tubular necrosis. In two different in vivo models (using multiple insults combined with the administration of Radiocontrast), iothalamate appeared to induce more severe morphologic injury. Despite similar nephrotoxic potential in vitro, the newer Radiocontrast Agents, iohexol and ioxaglate, cause in vivo less renal injury than iothalamate in the experimental models.
H. William Strauss - One of the best experts on this subject based on the ideXlab platform.
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Development of Radiocontrast Agents for Vascular Imaging
American Journal of Cardiovascular Drugs, 2002Co-Authors: Francis G. Blankenberg, Carina Marí, H. William StraussAbstract:The revolution in molecular imaging techniques is profoundly changing the understanding of the pathophysiology and treatment of atherosclerosis. With these rapid changes there is an increasing demand for development of sensitive and well tolerated novel imaging Agents that can be rapidly translated from small animal models into patients with atherosclerosis. Nuclear medicine and positron emission tomography techniques have the ability to detect and serially monitor a variety of biologic and pathophysiologic processes usually with tracer quantities of radiolabeled peptides, drugs, and other molecules at dosages free of pharmacologic adverse effects unlike the current generation of intravenous Agents required for magnetic resonance imaging (MRI) and computed axial tomography (CT) scanning. A representative sampling of the wide array of radiopharmaceuticals developed specifically for radionuclide imaging of atherosclerosis, that have been approved for clinical use and those in pre-clinical trials, have been reviewed in this article. The presence of an inflammatory stimulus increases expression of CC (cysteine-cysteine motif) chemokine receptor (CCR)-2 on monocytes and macrophages, and somatostatin receptors on T lymphocytes. Radiolabeled monocyte chemoattractant protein (MCP)-1 binds with high affinity to CCR-2 and can be used to detect subacute and chronic inflammatory lesions. Similarly, radiolabeled octreotide or depreotide can be used to detect activated T lymphocytes which may identify the vulnerable plaque. Animal models indicate that ^99mTc-annexin V, ^125I-MCP-1 and [^18F]-fluoro-2-deoxyglucose are effective in identifying apoptotic cell death, macrophage infiltration and metabolic activity in atheromatous lesions, respectively. Expression of α_vβ_3 integrin is increased in activated endothelial cells and vascular smooth muscle cells after vascular injury, and α_vβ_3 integrin is minimally expressed on smooth muscle cells and is not expressed on quiescent epithelial cells. Radiolabeled high-affinity peptides can be used to target the α_vβ_3 integrin and visualize areas of vascular damage. Advances in technology such as the micro-single photon emission computed tomography (microSPECT) have the potential to overcome the drawbacks of older CT and MRImethodologies, such as lack of biologically relevant ligands and compatible blood pool contrast Agents for imaging. Despite these advances in imaging technology, the small size of atheromatous lesions makes it difficult to detect using external imaging techniques. Therefore, recently there has been renewed interest in the use of intravascular catheter-based radiation detectors.
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Development of Radiocontrast Agents for Vascular Imaging
American journal of cardiovascular drugs : drugs devices and other interventions, 2002Co-Authors: Francis G. Blankenberg, Carina Marí, H. William StraussAbstract:The revolution in molecular imaging techniques is profoundly changing the understanding of the pathophysiology and treatment of atherosclerosis. With these rapid changes there is an increasing demand for development of sensitive and well tolerated novel imaging Agents that can be rapidly translated from small animal models into patients with atherosclerosis. Nuclear medicine and positron emission tomography techniques have the ability to detect and serially monitor a variety of biologic and pathophysiologic processes usually with tracer quantities of radiolabeled peptides, drugs, and other molecules at dosages free of pharmacologic adverse effects unlike the current generation of intravenous Agents required for magnetic resonance imaging (MRI) and computed axial tomography (CT) scanning.
Christlieb Haller - One of the best experts on this subject based on the ideXlab platform.
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The cytotoxicity of iodinated Radiocontrast Agents on renal cells in vitro.
Investigative radiology, 2004Co-Authors: Christlieb Haller, Istvan HizohAbstract:A deterioration of renal function is one preoccupying complication of iodinated Radiocontrast Agents in clinical practice. These compounds have direct toxic effects on renal cells, which are only in part related to their physicochemical properties. The hyperosmolal monomeric ionic Radiocontrast Agents, like diatrizoate, have the highest toxicity, whereas renal cells are less affected by (nonionic) compounds with reduced osmolality. The toxic effects include cellular energy failure, a disruption of calcium homeostasis, a disturbance of tubular cell polarity and programmed cell death (apoptosis). The molecular mechanisms of the direct cytotoxicity are still unclear, although oxidative stress has been implicated. Radiocontrast cytotoxicity has been demonstrated in glomerular mesangial cells and in renal epithelial cells in vitro. In vivo, the direct cellular toxicity of Radiocontrast Agents is compounded with alterations in blood flow and/or viscosity, ultimately resulting in renal medullary hypoxia, which is a hallmark feature of the complex clinical syndrome of Radiocontrast nephropathy.
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Comparative cytotoxicity of ionic and non-ionic Radiocontrast Agents on MDCK cell monolayers in vitro.
Nephrology dialysis transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 1999Co-Authors: Cornelia S. Schick, Christlieb HallerAbstract:Background. Intravascular Radiocontrast Agents may cause acute renal failure, particularly in patients with pre-existing renal insuYciency. Direct cytotoxic eVects of Radiocontrast Agents on renal tubular cells may Introduction contribute to the pathogenesis of Radiocontrastinduced nephropathy. Radiocontrast-induced nephropathy remains a Methods. We analysed the cytotoxicity of the ionic common complication of the intravascular application Radiocontrast Agents diatrizoate (monomeric) and iox- of Radiocontrast Agents, although the original highaglate (dimeric), as well as of the non-ionic radiocon- osmolal, ionic Radiocontrast Agents have been largely trast Agents iohexol (monomeric) and iodixanol superseded by newer compounds with considerably (dimeric) on the renal epithelial Madin Darby Canine lower osmolality. Although the newer Radiocontrast Kidney (MDCK ) cell line grown on permeable sup- Agents are generally better tolerated than the convenports. The toxicity assays assessed cell viability, trans- tional high-osmolal Agents, both ionic and non-ionic monolayer resistance and inulin permeability between compounds with reduced osmolality may still cause the apical and basal cell culture compartment. In renal failure, particularly in patients with renal addition, the distribution of the tight-junction- insuYciency prior to Radiocontrast exposure [1‐3]. associated membrane proteins ZO-1 and occludin was The reduction of the osmolality of the original ionic analysed using immunofluorescence microscopy. Radiocontrast Agents could be achieved in two ways: Results. In all assays the high osmolal ionic compound first, rendering the original ionic monomeric comdiatrizoate had significant cytotoxic eVects that pounds dimeric and second, preventing their dissociincluded the partial redistribution of the tight-junction- ation in watery solutions, i.e. rendering the ionic associated membrane proteins into a cytoplasmic com- compounds non-ionic. In addition to the dimeric ionic partment. To a lesser extent this redistribution also compound ioxaglate, a variety of non-ionic radioconoccurred with the dimeric ionic compound ioxaglate, trast Agents with reduced osmolality are available, both but not with the non-ionic Radiocontrast Agents. With monomeric and dimeric. There is general agreement regards to cell viability, transmonolayer resistance and that the profoundly hyperosmolal monomeric ionic inulin permeability the Radiocontrast Agents with Agents have the highest toxicity, but the diVerential reduced osmolality were significantly less toxic nephrotoxicity of the Radiocontrast Agents with reduced than diatrizoate, independent of their ionic strength. osmolality and the role of ionic strength have not been Conclusions. Physicochemical factors contribute to the analysed in detail. cytotoxicity of Radiocontrast Agents in vitro. The redis- The pathogenesis of Radiocontrast-induced nephrotribution of tight-junction-associated membrane pro- pathy has been attributed to haemodynamically mediteins by the ionic Radiocontrast Agents corresponds ated renal medullary hypoxia [4,5]. However, direct with the loss of the barrier function of the epithelial cytotoxic eVects of Radiocontrast Agents on renal epicell monolayer, which is a major pathophysiological thelial cells may contribute to the renal tubular injury. mechanism in acute renal failure. The Radiocontrast This direct cytotoxicity has been shown in isolated Agents with reduced osmolality are less cytotoxic than renal tubules and in renal epithelial cells in vitro and diatrizoate, independent of their ionicity. Hyperos- may involve changes in cellular energy metabolism molality appears to be a more important determinant [6,7], release of intracellular enzymes [8], disruption of the cytotoxicity of diatrizoate than ionic strength. of renal epithelial cell monolayers with an altered distribution of polarized plasmalemmal marker pro
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Cytotoxicity of Radiocontrast Agents on polarized renal epithelial cell monolayers
Cardiovascular research, 1997Co-Authors: Christlieb Haller, Cornelia S. Schick, Markus Zorn, Wolfgang KüblerAbstract:Objective: Radiocontrast-induced nephropathy is a clinically important complication of coronary angiography. The cellular mechanisms of Radiocontrast-induced renal dysfunction are not clear. Since tubular transport functions depend on the polarity of renal epithelial cells, we investigated the effects of Radiocontrast Agents on polarized tubular cells in vitro. Methods: We studied the effects of iso-iodine concentrations (37 and 74 mg iodine/ml) of an ionic (diatrizoate) and a non-ionic (iopamidol) monomeric Radiocontrast agent and of hyperosmolal mannitol control solutions on filter-grown renal epithelial cell (MDCK, LLCPK) monolayers in vitro. The cytotoxicity was assayed by measurement of cell viability, transepithelial resistance, inulin permeability and (polarized) cellular enzyme release. The polarized MDCK cell phenotype was assessed by transmission electron microscopy and indirect immunofluorescence microscopy using monoclonal antibodies against specific apical (gp135) and basal (gp60, uvomorulin) MDCK surface markers. Results: The Radiocontrast Agents reduced cell viability to a greater extent than hyperosmolal mannitol solutions in both cell lines; diatrizoate was more toxic than iopamidol. LLCPK cells were more susceptible to Radiocontrast cytotoxicity than MDCK cells. This cytotoxicity was associated with an alteration of MDCK cell polarity as assessed by the redistribution of surface marker proteins. Conclusions: Diatrizoate is more toxic than iopamidol, which is partly related to its higher osmolality. The cytotoxicity of Radiocontrast Agents induces a redistribution of polarized membrane proteins which could contribute to the pathophysiology of Radiocontrast-induced nephropathy.
Seymour Rosen - One of the best experts on this subject based on the ideXlab platform.
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Renal Parenchymal Hypoxia, Hypoxia Adaptation, and the Pathogenesis of Radiocontrast Nephropathy
Clinical Journal of The American Society of Nephrology, 2007Co-Authors: Samuel N. Heyman, Seymour Rosen, Christian RosenbergerAbstract:Background and objectives: Renal parenchymal Po2 declines after the administration of iodinated Radiocontrast Agents, reaching critically low levels of approximately 10 mmHg in medullary structures. Design, setting, participants, & measurements: In this review, the causes of renal parenchymal hypoxia and its potential role in the pathogenesis of contrast nephropathy are appraised. Results: Commonly associated predisposing factors are associated with a propensity to enhance renal hypoxia. Indeed, animal models of Radiocontrast nephropathy require the induction of such predisposing factors, mimicking clinical scenarios that lead to contrast nephropathy in high-risk individuals. In these models, in association with medullary hypoxic damage, a transient local cellular hypoxia response is noted, initiated at least in part by hypoxia-inducible factors. Some predisposing conditions that are distinguished by chronically aggravated medullary hypoxia, such as tubulointerstitial disease and diabetes, are characterized by a priori upregulation of hypoxia-inducible factors, which seems to confer tolerance against Radiocontrast-related hypoxic tubular damage. Renal dysfunction under such circumstances likely reflects to some extent altered intrarenal hemodynamics, rather than acute tubular injury. Conclusions: Real-time, noninvasive novel methods may help to differentiate between evolving tubular damage and altered hemodynamics and in the design of appropriate preventive interventions.
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Effects of ioversol versus iothalamate on endothelin release and Radiocontrast nephropathy.
Investigative radiology, 1993Co-Authors: Samuel N. Heyman, Mayer Brezis, Seymour Rosen, Barbara A. Clark, Lloyd G. Cantley, Katherine Spokes, Franklin H. EpsteinAbstract:RATIONALE AND OBJECTIVES Certain Radiocontrast Agents, including iothalamate, iohexol, and ioxaglate, release the renal vasoconstrictor peptide endothelin from vascular endothelium in a way that might contribute to Radiocontrast nephropathy. The effects of the nonionic, low osmolar agent, ioversol, on endothelin release and renal function are investigated. METHODS Effects of ioversol were compared with equi-iodine doses of iothalamate when applied to cultured bovine aortic endothelial cells or injected into normal rats and rats preconditioned by uninephrectomy, salt depletion, and indomethacin (USIC) to develop Radiocontrast nephropathy. RESULTS In comparison with iothalamate, ioversol had a greatly reduced propensity to stimulate the release of endothelin, from cultured cells and when injected into anesthetized rats. Ioversol produced less renal vasoconstriction than did iothalamate, in control and in USIC rats, and the development of Radiocontrast nephropathy, assessed by creatinine clearance and morphologic damage to the renal medulla, was largely avoided. CONCLUSIONS These results strengthen the hypothesis that endothelin release induced by Radiocontrast Agents is correlated with their renal toxicity and therefore, may play a role in Radiocontrast nephropathy.
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Radiocontrast Agents induce endothelin release in vivo and in vitro.
Journal of the American Society of Nephrology : JASN, 1992Co-Authors: Samuel N. Heyman, Mayer Brezis, Seymour Rosen, Barbara A. Clark, Katherine Spokes, N. Kaiser, Franklin H. EpsteinAbstract:The intravascular administration of the ionic Radiocontrast agent sodium iothalamate (2.9 g of iodine/kg body wt) to rats induced an increase in plasma concentration of immunoreactive endothelin from 21.3 +/- 1.2 to 36 +/- 3 fmol/mL, preceded by a transient rise in the plasma level of atrial natriuretic peptide and associated with a fall in RBF. Equi-iodine amounts of the nonionic Agents ioxaglate and iohexol elicited similar or more marked changes in plasma endothelin, but hypertonic solutions of NaCl, mannitol, or glucose did not. Comparable levels of endothelin produced by infusions of endothelin-1 induced a reduction of up to 29% in RBF. Iothalamate and iohexol stimulated endothelin release from cultured bovine endothelial cells, suggesting a direct effect of ionic and nonionic Agents on vascular endothelium. The data invite speculation that under some circumstances endothelin release might play a role in the circulatory changes caused by these compounds and in the pathogenesis of Radiocontrast nephropathy.
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Experimental nephrotoxicity of the Radiocontrast Agents iohexol, ioxaglate, and iothalamate. An in vitro and in vivo study.
Investigative radiology, 1991Co-Authors: Mayer Brezis, Greenfeld Z, Herman M, Samuel N. Heyman, Seymour RosenAbstract:The authors compared the renal toxicity of the low osmolality Radiocontrast Agents, iohexol and ioxaglate, and the ionic agent, iothalamate, at equivalent iodine dose, using experimental models in vitro and in vivo. In isolated perfused rat kidneys, all Agents induced comparable biphasic hemodynamic changes, associated with similar declines in glomerular filtration rate (GFR) and tubular necrosis. In two different in vivo models (using multiple insults combined with the administration of Radiocontrast), iothalamate appeared to induce more severe morphologic injury. Despite similar nephrotoxic potential in vitro, the newer Radiocontrast Agents, iohexol and ioxaglate, cause in vivo less renal injury than iothalamate in the experimental models.
Mayer Brezis - One of the best experts on this subject based on the ideXlab platform.
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Effect of Radiocontrast Agents on Intrarenal Nitric Oxide (NO) and NO Synthase Activity
Experimental nephrology, 1998Co-Authors: Samuel N. Heyman, Marina Goldfarb, Fanni Carmeli, Ahuva Shina, Daniel Rahmilewitz, Mayer BrezisAbstract:Background/Aims: Contrast media (CM) induce a biphasic renal hemodynamic response, with late prominent cortical vasoconstriction and marked outer medullary vasodilation. The objecti
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Effects of ioversol versus iothalamate on endothelin release and Radiocontrast nephropathy.
Investigative radiology, 1993Co-Authors: Samuel N. Heyman, Mayer Brezis, Seymour Rosen, Barbara A. Clark, Lloyd G. Cantley, Katherine Spokes, Franklin H. EpsteinAbstract:RATIONALE AND OBJECTIVES Certain Radiocontrast Agents, including iothalamate, iohexol, and ioxaglate, release the renal vasoconstrictor peptide endothelin from vascular endothelium in a way that might contribute to Radiocontrast nephropathy. The effects of the nonionic, low osmolar agent, ioversol, on endothelin release and renal function are investigated. METHODS Effects of ioversol were compared with equi-iodine doses of iothalamate when applied to cultured bovine aortic endothelial cells or injected into normal rats and rats preconditioned by uninephrectomy, salt depletion, and indomethacin (USIC) to develop Radiocontrast nephropathy. RESULTS In comparison with iothalamate, ioversol had a greatly reduced propensity to stimulate the release of endothelin, from cultured cells and when injected into anesthetized rats. Ioversol produced less renal vasoconstriction than did iothalamate, in control and in USIC rats, and the development of Radiocontrast nephropathy, assessed by creatinine clearance and morphologic damage to the renal medulla, was largely avoided. CONCLUSIONS These results strengthen the hypothesis that endothelin release induced by Radiocontrast Agents is correlated with their renal toxicity and therefore, may play a role in Radiocontrast nephropathy.
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Radiocontrast Agents induce endothelin release in vivo and in vitro.
Journal of the American Society of Nephrology : JASN, 1992Co-Authors: Samuel N. Heyman, Mayer Brezis, Seymour Rosen, Barbara A. Clark, Katherine Spokes, N. Kaiser, Franklin H. EpsteinAbstract:The intravascular administration of the ionic Radiocontrast agent sodium iothalamate (2.9 g of iodine/kg body wt) to rats induced an increase in plasma concentration of immunoreactive endothelin from 21.3 +/- 1.2 to 36 +/- 3 fmol/mL, preceded by a transient rise in the plasma level of atrial natriuretic peptide and associated with a fall in RBF. Equi-iodine amounts of the nonionic Agents ioxaglate and iohexol elicited similar or more marked changes in plasma endothelin, but hypertonic solutions of NaCl, mannitol, or glucose did not. Comparable levels of endothelin produced by infusions of endothelin-1 induced a reduction of up to 29% in RBF. Iothalamate and iohexol stimulated endothelin release from cultured bovine endothelial cells, suggesting a direct effect of ionic and nonionic Agents on vascular endothelium. The data invite speculation that under some circumstances endothelin release might play a role in the circulatory changes caused by these compounds and in the pathogenesis of Radiocontrast nephropathy.
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Experimental nephrotoxicity of the Radiocontrast Agents iohexol, ioxaglate, and iothalamate. An in vitro and in vivo study.
Investigative radiology, 1991Co-Authors: Mayer Brezis, Greenfeld Z, Herman M, Samuel N. Heyman, Seymour RosenAbstract:The authors compared the renal toxicity of the low osmolality Radiocontrast Agents, iohexol and ioxaglate, and the ionic agent, iothalamate, at equivalent iodine dose, using experimental models in vitro and in vivo. In isolated perfused rat kidneys, all Agents induced comparable biphasic hemodynamic changes, associated with similar declines in glomerular filtration rate (GFR) and tubular necrosis. In two different in vivo models (using multiple insults combined with the administration of Radiocontrast), iothalamate appeared to induce more severe morphologic injury. Despite similar nephrotoxic potential in vitro, the newer Radiocontrast Agents, iohexol and ioxaglate, cause in vivo less renal injury than iothalamate in the experimental models.