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OBJECTIVES: The objective of this study was to assess whether streptozotocin (STZ)-induced diabetic rats develop iodinated contrast-induced acute kidney injury. The intrarenal R2* (=1/T2*) was evaluated continuously before, during, and after contrast administration. Renal injury was confirmed using urinary neutrophil gelatinase-associated lipocalin measurements. MATERIALS AND METHODS: Six Sprague-Dawley rats were administered with STZ to induce diabetes (group 1). R2* was measured before, during, and after administration of iodixanol. R2* readings were sampled from 4 renal regions: inner medulla, inner stripe of outer medulla (ISOM), outer stripe of outer medulla, and cortex. Peak R2* and initial upslope of R2* increase after iodinated contrast were calculated. Data from 12 nondiabetic rats pretreated with nitric oxide synthase and prostaglandin inhibitors to induce susceptibility to contrast-induced acute kidney injury (pretreatment model) from a previous study were reanalyzed for peak R2* and initial upslope of R2* increase after contrast. Six of these animals received saline (group 2), and the other 6 received furosemide (group 3) before iodixanol. RESULTS: Peak R2* and initial upslope of R2* increase were used as blood-oxygenation-level-dependent response parameters. R2* in ISOM was comparable in all 3 groups before administration of furosemide/saline. Except for the furosemide group, ISOM showed a rapid increase in R2* immediately after contrast administration. Unlike the L-NAME- and indomethacin-treated groups, the diabetic group showed a quick reversal of R2* toward baseline measurements after contrast administration. Urinary neutrophil gelatinase-associated lipocalin indicated significant increase in diabetic rats 4 hours after contrast administration. The observed trends with peak R2* and initial upslope of R2* increase in renal ISOM were in agreement with those of urinary neutrophil gelatinase-associated lipocalin. CONCLUSIONS: The STZ-induced diabetic rat may be suitable for studying the effects of iodinated contrast on renal oxygenation status and may mimic human condition closer than the pretreatment model described before. The peak R2* value and initial upslope of R2* in ISOM appear to be effective magnetic resonance imaging markers to predict renal injury after administration of an iodinated contrast agent.

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PURPOSE: To compare changes in urinary viscosity in the renal tubules following administration of a high-viscosity iso-osmolar contrast agent (iodixanol) to that observed following administration of a less viscous, higher osmolar contrast agent (iopromide) in anesthetized rats. MATERIALS AND METHODS: A total of 43 rats were studied. Experiments were approved by the Berlin, Germany, animal protection administration. A viscometer was developed to measure viscosity in minute samples (7 microL). Urine was collected, viscosity was measured (at 37 degrees C), and glomerular filtration rate (GFR) was determined by means of creatinine clearance. Boluses of 1.5 mL of iodixanol (320 mg iodine per milliliter, iso-osmolar to plasma, high viscosity) or iopromide (370 mg iodine per milliliter, higher osmolality and lower viscosity than iodixanol) were injected into the thoracic aorta. There were five groups (seven rats per group). Groups 1 (iodixanol) and 2 (iopromide) had free access to water prior to the experiment; groups 3 (iodixanol) and 4 (iopromide) received an additional infusion of isotonic saline (4 mL/kg/h). Group 5 was treated as group 1 but received only 0.75 mL of iodixanol. The observation period was 100 minutes. Statistical comparisons were made by means of nonparametric procedures (Friedman test, Kruskal-Wallis test). RESULTS: Iodixanol increased urine viscosity from 0.69 to 36.7 mm(2)/sec; thus, urine became threefold more viscous than native iodixanol solution. The increase in urine viscosity after injection of iopromide was from 0.73 to 2.3 mm(2)/sec. While GFR was not significantly affected by iopromide, GFR transiently decreased by 50% after administration of iodixanol. Iopromide had a diuretic effect twofold greater than that of iodixanol. Saline infusion blunted the viscosity rise and transient decline in GFR caused by iodixanol, as did reducing the iodixanol dose by 50%. CONCLUSION: Contrast media, in particular iodixanol, increase urine viscosity (which is equal to tubular fluid viscosity in the collecting ducts); in response to iodixanol, GFR markedly decreases. Saline infusion attenuates this response, thus potentially explaining the protective effects of volume expansion in contrast medium-induced nephropathy.

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BACKGROUND: Intestinal ischaemia may be difficult to recognize in the early stages. Increased urinary recovery of water-soluble contrast medium during and intestinal follow-through has been suggested as a sign of bowel ischaemia. METHODS: Urinary excretion of the isosmolar water-soluble X-ray contrast medium iodixanol was measured after instillation via an orogastric tube in 56 rats with occlusion of the mesenteric blood vessels. RESULTS: Mesenteric venous occlusion caused only minor histologic alterations of the mucosa. High-performance liquid chromatography (HPLC) and X-ray fluorescence analysis measured urinary iodixanol concentrations 10 and 13 times higher than in the groups with mesenteric arterial occlusion than in controls (p < 0.001), and 3 and 4 times higher than in the group with venous occlusion (p < or = 0.05). Correlation between HPLC and X-ray fluorescence measurements of contrast medium in urine was strong (r = 0.98). CONCLUSION: Measuring urinary contrast medium levels during intestinal follow-through may aid in distinguishing bowel ischaemia following mesenteric arterial occlusion from mesenteric venous occlusion and from the normal bowel.

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RATIONALE AND OBJECTIVES: The authors compared the safety and pharmacokinetics of Iotrolan (water-soluble) in hysterosalpingography (HSG) with those of Lipiodol (oil-soluble). METHODS: Iotrolan and Lipiodol were administered intraperitoneally at doses of 100 mg iodine/kg to female rabbits. Retention in the body was investigated by x-ray imaging, plasma kinetics, and urinary and fecal excretion. Irritability in the abdomen was investigated by histologic examination. RESULTS: Iotrolan was entirely excreted into the urine within 2 days after administration. Conversely, Lipiodol was excreted into the urine, had a half-life of 50 days, and was retained for more than 21 days in the abdomen. Iotrolan induced no inflammatory reaction in the abdomen, whereas Lipiodol induced a marked abdominal inflammatory reaction, including granuloma formation. Iotrolan had no effect on iodine concentration in the thyroid; Lipiodol increased iodine concentration significantly. CONCLUSIONS: Iotrolan, which is a water-soluble and nonionic dimeric contrast medium, has potential greater safety for use in HSG than Lipiodol.

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Iopentol 350 mg I/ml was injected in doses of 265 to 533 mg I/kg b.w. (mean 417 mg I/kg b.w.) in 10 patients with advanced nondiabetic chronic renal failure (S-creatinine 672 +/- 259 mumol/l (mean +/- SD)). Urine (10 patients) and feces (7 patients) were collected at 24 h intervals for 5 days after the injection. The elimination of iopentol was delayed. Five days after injection a mean of 54% (range 35-79%) of the dose was recovered in urine, and 11% (0-20%) in feces. Mean elimination half-life was 28.4 h, about 14 times the half-life found in healthy volunteers. The apparent volume of distribution was 0.27 l/kg b.w., indicating distribution only to extracellular fluid. Using renal iopentol clearance as reference value, GFR was overestimated by 40 to 60% with iopentol total clearance, showing extrarenal elimination of iopentol. The difference was most pronounced in patients with low GFR. In conclusion, this study shows an extrarenal elimination of iopentol and demonstrates a substantial increase in the fecal elimination in patients with severe renal failure.

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The pharmacokinetics of iohexol, a new nonionic, water-soluble contrast medium, have been determined after intravenous injection in 20 healthy volunteers, at four different dose levels (125-500 mg I/kg). The apparent volume of distribution was 0.27 1/kg, indicating distribution in the extracellular water. The biologic half-life was 121 minutes, comparable with that of other intravascular contrast media. Iohexol was excreted completely unmetabolized in the urine, with a 100% recovery 24 hours after injection. A comparison of iohexol and chromium-51 (51Cr)-EDTA clearances indicates that iohexol is mainly excreted by glomerular filtration. The 51Cr-EDTA clearance was the same when injected separately and concomitantly with iohexol, indicating that glomerular filtration rate is not affected by iohexol. No dose dependency was observed in the investigated parameters t1/2 alpha, t1/2 beta, Vd, ClT or ClR. Iohexol pharmacokinetics are in correspondence with previously reported data on intravascular contrast media.

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Pharmacokinetical properties of eight triiodobenzene derivatives, X-ray contrast agents, were studied in the hemoglobin-free perfused rat liver with emphasis on the structural relation to biliary transport. With chemical modification of the basic structure, these agents showed different characteristics in the processes of diffusion into hepatocytes, accumulation in the cells and active transport into the bile, and were separated into four groups; [I]: Iotroxic acid (1), Iodipamic acid (2), Iodoxamic acid (3), and Ioglycamic acid (4) which showed faster rates of diffusion into hepatocytes [(1) greater than or equal to (2) greater than (3) greater (4)] and also of biliary excretion [(1) greater than (2) greater than (4) greater than (3)], [II]: Diatrizoic acid and Metrizamide showed poor diffusion and biliary excretion, [III]: Iopodic acid showed the highest permeability into and accumulation in hepatocytes with little biliary excretion, [IV]: ZK73 215 was slowly transported into the bile, yet, showed little permeation through the cell membrane. Characteristics of (1), (2) and (3) observed in the perfused liver were, in principle, confirmed in the pharmacokinetical profile observed in vivo. However, the fast diffusion of (2) into the hepatocytes appears to be hampered by high binding ability with serum proteins, whereas the relatively poor profile of the biliary excretion of (3) was improved by its low protein-binding in blood in vivo. Superiority of (1) as a cholangiographic agent was demonstrated by the fast biliary excretion in both the case of experimental systems and moderate protein-binding.

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Iodipamide and iodoxamate were compared in equimolar clinical dosages in five cholecystectomized chronic bile fistula dogs in which hepatic dysfunction was produced by oral administration of a total dose of 480 and 960 microliters dimethylnitrosamine (DMNA), respectively. After both DMNA dosages, the peak biliary excretion rate for iodoxamate was significantly higher than for iodipamide (p less than 0.01). The peak bile iodine concentration was not significantly different for the two agents (480 microliter DMNA: p less than 0.1; 960 microliter DMNA: p = 0.07). On the basis of this investigation, it is suggested that iodoxamate should not significantly improve the opacification of the biliary system in patients with hepatic dysfunction.

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The biliary excretion and choleretic effects of iodoxamate (Cholevue) and iodipamide (Cholografin) were compared in unanesthetized dogs with biliary fistulas in order to assess the potential of the two contrast agents for use in intravenous cholangiography. For any equimolar infusion rate, more iodoxamate was secreted in the bile than iodipamide was the same. At the constant basal bile flow maintained in these studies, there was no difference in the maximum biliary concentration of the two compounds. With the presently recommended doses, it is unlikely that iodoxamate will offer a striking improvement over iodipamide for intravenous cholangiography in patients with normal liver function.

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