A comparison of the systemic responses to rapid intravenous injections of ioxilan, iohexol, and diatrizoate in rabbits

Rapid intravenous injections of contrast media are used for angiocardiography, intravenous digital subtraction angiography (DSA), and rapid scan computed tomography procedures. These rapid intravenous injections have been shown to produce significant hemodynamic changes that appear related to contrast media osmolality. In this study the systemic responses to 2-second injections at a dose of 1.5 mL/kg were compared for a new nonionic agent, ioxilan (350 mgI/mL), and for iohexol (350 mgI/mL), meglumine/sodium diatrizoate (370 mgI/mL), and saline. Ioxilan has a lower osmolality and viscosity than iohexol and is formulated with a 3 mM sodium citrate as a buffer and anticoagulant. All of the test solutions produced statistically significant changes in arterial pressure and respiratory rate (P less than .05, Student's t-test). The decrease in arterial pressure seen with diatrizoate (20.1%) was significantly greater than the decrease seen with either ioxilan (10.2%) or iohexol (10.2%). All of the responses observed were transient and would not be of clinical concern in a healthy patient. Ioxilan, which contains the calcium binding agent, sodium citrate, and iohexol appear to cause less systemic effects then diatrizoate.     

Intravenous injection of ioxilan, iohexol and diatrizoate. Effects on urine profiles in the rat

Effects of intravenous ioxilan, a new third generation non-ionic contrast medium, diatrizoate, iohexol and saline on urine profiles were compared. Albumin, glucose, sodium, phosphate, and the enzymes NAG, LDH and GGT were followed in 24 normal rats over 7 days. Diatrizoate significantly affected all profile components during the first two hours. Albuminuria was significantly greater after diatrizoate than after iohexol or ioxilan, and excretion of glucose, LDH and GGT was significantly higher than after ioxilan. Both iohexol and ioxilan increased the excretion of albumin, LDH and GGT, while iohexol also significantly increased excretion of glucose and sodium. There was a greater excretion of glucose and GGT after iohexol than after ioxilan. Saline did not induce any changes. At day 7, serum sodium, urea, creatinine, and albumin were normal for all test substances, and kidney histology revealed no difference between the groups of animals. It is thus concluded that both high osmolar ionic and low osmolar non-ionic contrast media may cause temporary glomerular and tubular dysfunction in rats. In this model, the kidney is affected most by diatrizoate, less by iohexol, and least by ioxilan.     

Nephropathy induced by intramuscularly administered glycerol and contrast media in rats. A comparison between diatrizoate, iohexol and ioxilan

Urine profiles (albumin, glucose, NAG, LDH, GGT, sodium, and phosphate) were followed for 14 days after intravenous injection of either diatrizoate, iohexol, ioxilan, or saline in 24 Wistar rats with a glomerular and tubular dysfunction induced by intramuscularly (i.m.) administered glycerol. Another 6 rats exposed to neither glycerol nor contrast media served as controls. The effect of ioxilan and saline on the albumin excretion was similar, whereas diatrizoate and iohexol increased it significantly. The contrast media had no further inhibitory effect on the reabsorption of glucose. Iohexol caused significantly increased excretion of all three enzymes, ioxilan of NAG and LDH, whereas diatrizoate only increased the excretion of LDH. The sodium excretion was further increased by ioxilan and diatrizoate, whereas none of the contrast media affected the phosphaturia. Both ioxilan and iohexol caused a round cell response around the tubules shown by light microscopy whereas diatrizoate caused no further changes. It is concluded that diatrizoate and iohexol increase glomerular dysfunction induced by glycerol i.m.; all three contrast media cause some further increase in the tubular dysfunction. Neither diatrizoate, iohexol nor ioxilan prolong nephropathy induced by glycerol i.m. determined by the chemical analyses. The histologic finding indicates a direct toxic effect of non-ionic low osmolar contrast media in this animal model of nephropathy.     

A randomized trial of prophylactic acetylcysteine and theophylline compared with placebo for the prevention of renal tubular vacuolization in rats after iohexol administration

RATIONALE AND OBJECTIVES: Renal tubular vacuolization (RTV), which has been shown to occur after the use of iodinated contrast material, may be one of the earliest signs of contrast medium-induced renal injury. In this study, the authors tested a method for preventing RTV with the administration of acetylcysteine, theophylline, or both, prior to contrast medium administration. MATERIALS AND METHODS: Eighty rats were randomly selected for inclusion in the study. The treatment group consisted of three subgroups, each of which received prophylactic acetylcysteine, theophylline, or both before injection of iohexol. The control group comprised five subgroups, each of which received acetylcysteine, theophylline, both, normal saline injection, or orally administered normal saline prior to iohexol injection. RESULTS: The occurrence of RTV in the treatment groups was compared with that in the control subgroup that received normal saline and iohexol. All of the rats in that control subgroup (n = 10) and 97% of the rats in the treatment group (n = 30) developed RTV. CONCLUSION: The administration of acetylcysteine, theophylline, or both prior to iohexol injection did not prevent RTV from occurring in rats.     

Gadolinium contrast media are more nephrotoxic than a low osmolar iodine medium employing doses with equal X-ray attenuation in renal arteriography: an experimental study in pigs

RATIONALE AND OBJECTIVES: To investigate in a unilaterally nephrectomized porcine model whether gadolinium contrast media (Gd-CM) are less nephrotoxic than iodine media (I-CM) in x-ray arteriography of a kidney made temporarily ischemic by arterial balloon occlusion. MATERIALS AND METHODS: In a noncrossover design, 3 mL of each test solution were injected in eight pigs (mean weight 19 kg) at a rate of 20 mL/min into the right renal artery at the start of a 10-minute period of ischemia. In group 1 (40 pigs) we injected 0.5 M gadopentetate, 0.5 M gadodiamide, 0.5 M iohexol (190 mg I/mL), 0.18 M iohexol (70 mg I/mL; with an x-ray attenuation equal to that of 0.5 M Gd-CM at 80 kV), and saline. In group 2 (24 pigs), we tested 0.18 M iohexol with ischemia and saline with and without ischemia. Gd- and iodine contrast media functioned as markers of glomerular filtration rate (GFR). When saline was tested, a low dose of iohexol (3 mL per pig; 300 mg I/mL) was injected as GFR marker intravenously in group 1 and into the renal artery in group 2. The plasma half-life elimination times of the CM 1-3 hours after injection were used to compare the effects of the different test solutions on GFR. Longer half-life means lower GFR. RESULTS: Group 1: median plasma half-life elimination time of the GFR marker was 3 340 minutes after injection of 0.5 M gadopentetate, 256 after 0.5 M gadodiamide, 179 after 0.5 M iohexol, 143 after 0.18 M iohexol, and 133 minutes after saline. All differences except that between 0.18 M iohexol and saline were statistically significant (P < .01). Group 2: median plasma half-life was 174 minutes after 0.18 M iohexol with ischemia, 196 minutes after saline with ischemia, and 195 minutes after saline without ischemia. There were no significant differences between the test solutions in group 2 (P > .05). CONCLUSION: In pigs, 0.5 M Gd-CM were more nephrotoxic than both equal-attenuating (70 mg I/mL) and equimolar (190 mg I/mL) concentrations of the I-CM iohexol. These results do not support the "off-label" use of Gd-CM for renal x-ray arteriography in man instead of commercially available concentrations of iodine contrast media at 140, 150 and 180 mg I/mL or diluted to 70 mg I/mL.     

A model for research on the blood-brain barrier disruption induced by unsaturated fatty acid emulsion

PURPOSE: The authors investigated whether fatty acid emulsion affects the blood-brain barrier (BBB), whether disrupted BBB is reversible, and whether the fatty acid emulsion technique may be a model for BBB research. MATERIALS AND METHODS: The fat emulsion was made with 0.05 mL of oleic acid or linoleic acid and 20 mL of normal saline. The internal carotid artery in 14 cats was infused with oleic acid emulsion (group 1) and with linoleic acid emulsion in 12 cats (group 2). Gd-enhanced T1-weighted (Gd-T1WI), diffusion-weighted (DWI), and additional apparent diffusion coefficient (ADC) map magnetic resonance imaging (MRI) was obtained at 1 hour, 1 and 4 days, and 1 week after infusion. MRI findings were evaluated qualitatively. Quantitatively, the signal intensity ratio (SIR) of the lesion to the contralateral hemisphere was measured on Gd-T1WIs. The SIRs were statistically analyzed using the student t test. The brain tissue was removed immediately for light and electron microscopy examination if the lesion showed no contrast enhancement and was isointense on DWIs and the ADC maps. RESULTS: The lesions appeared at 1 hour in both groups as contrast enhancement on Gd-T1WIs, as isointensity or mild hyperintensity on DWIs, and as isointensity on the ADC maps. On day 1, these MRI findings were decreased in group 1 and were not seen in group 2. At 1 hour, the SIRs of group 1 were significantly higher than those of group 2 (P = 0.016). On day 1, the SIRs of both groups approximated 1.0. Light microscopy findings revealed minor necrosis and demyelination in one cat from group 1 and in 3 cats from group 2. Electron microscopy examinations showed minimal findings in the cortical lesions in groups 1 and 2. CONCLUSIONS: Infusion of unsaturated fatty acid emulsion into the carotid artery of cats revealed vasogenic edema of the brain and reversible changes as depicted on MRI. This unsaturated fat emulsion technique may be used as a model for research on BBB disruption.     

Direct effects of contrast media on rat lungs

Despite the widespread use and the assumed safety of Omnipaque (iohexol) and 3% Gastrografin (meglumine diatrizoate) as contrast media for esophagography and computed tomography respectively, their effects on the lung if they are aspirated have never been studied. This information is important because such compounds may inadvertently enter the lungs during the diagnostic procedures. Twenty-four rats were injected intratracheally with 0.15 mL of one of three contrast agents (omnipaque, full-strength Gastrografin and 3% Gastrografin) or normal saline, which was used as a control. Radiographs were then obtained. Equal numbers from each experimental group were sacrificed after 5 minutes, 1 hour and 24 hours, and their lungs were examined pathologically. The rats injected with full-strength Gastrografin all died immediately of gross pulmonary edema. Neither Omnipaque nor 3% Gastrografin was fatal, but Omnipaque produced more edema and alveolar hemorrhage than either normal saline or 3% Gastrografin. Iohexol is, therefore, more irritating to the airways and the lung parenchyma than previously believed.     

碱性成纤维细胞生长因子对受照后大鼠血脑屏障的影响

目的评价定量检测放射性血脑屏障（BBB）破坏的不同方法，探讨碱性成纤维细胞生长因子（bFGF）对放射性BBB破坏的保护作用。方法60只急性放射性脑损伤模型大鼠（直线加速器6MeV电子束单次照射25Gy）分为单纯照射组和照射前尾静脉注射bFGF组（250ng／kg），并设未照射对照组；分别于照射后2、7和30d采用脑干-湿重法检测脑含水量，并用单次静脉注射3mg／kg伊文氏蓝（EB）后脑组织的EB含量法评估BBB破坏情况。结果照射后脑组织含水量和EB含量均较对照组明显增高，注射bFGF组脑组织含水量和EB含量均低于单纯照射组（P〈0．05）。受照后不同日期的脑组织EB含量差异有统计学意义（P〈0．05），而脑含水量差异没有统计学意义。结论注射EB后检测脑组织，浓度法较干湿重法测脑含水量能更好地反映BBB的破坏情况；bFGF对受照后BBB破坏有保护作用。     

Contrast media-induced blood-brain barrier damage. Potentiation by hypertension

Large doses of an ionic contrast medium (CM) can disrupt the blood brain barrier (BBB) osmotically. Acute hypertension (HT) also is known to open the BBB. We tested the hypothesis that these two factors potentiate each other in a rat model. Adult male Wistar rats, anesthetized with pentobarbital, underwent tracheostomy. An external carotid artery catheter was placed so that it opened into the patent common carotid artery; arterial blood pressure was recorded continuously. Of three groups of animals, two (HT) groups received metaraminol to elevate and maintain blood pressure in the range of 165 to 190 mm Hg. The third (normotensive) group received an equivalent volume of saline. Five minutes after injection of Evan's blue, either sodium/meglumine diatrizoate or saline was infused into the carotid cannula (2 mL in 30 seconds). Twenty minutes later the cardiovascular system was flushed with saline, and the brain was removed, frozen, and sectioned for gross and histofluorescent microscopic examination of BBB opening. The carotid injection of CM at a concentration of 1000 mosm/kg water did not produce gross evidence of BBB opening in the normotensive group. Similarly, hypertension at levels below 190 mm Hg did not produce gross evidence of opening in the carotid saline group. However, the combination of carotid CM and HT produced significant BBB opening. These results suggest that the risk factor of acute HT potentiates CM-induced BBB opening.     

Effects of nonionic contrast media on the blood-brain barrier. Osmolality versus chemotoxicity.

This study was performed to assess the relative contributions of contrast medium osmolality and chemotoxicity to contrast-induced blood-brain barrier (BBB) damage. Experimental carotid angiography was carried out in rabbits with mannitol at an osmolality of 714 mOsm/kg, with the nonionic, monomeric contrast media iohexol and ioversol at similar osmolalities, and with the nonionic, dimeric contrast media iodixanol and iotrolan at osmolalities less than half that of the mannitol. The amount of damage caused by the procedure was assessed by determining the amount of intracerebral extravasation of intravascularly injected technetium-99m-pertechnetate. Mannitol caused no detectable BBB damage, but all four contrast media caused BBB damage that was significantly more severe than that caused by mannitol. The BBB damage caused by carotid angiography with iohexol, ioversol, iodixanol, and iotrolan was not attributable to their osmolalities, but due to some other physical and/or chemical effects of these media on the BBB.     

Cytogenetic interactions of contrast media and antineoplastic drugs

The cytogenetic interactions of ionic (diatrizoate, ioxaglate) and nonionic (iohexol) contrast media (CM) with antineoplastic drugs cyclophosphamide (CPA) and carmustine (CARM) were evaluated in a rat bone marrow cell model. Male Wistar rats were anesthetized with a 6% chloral hydrate solution and divided into five groups of five rats each. In protocol 1, three groups of rats received diatrizoate, ioxaglate, and iohexol (2.5 mL/kg) intravenously within 30 seconds. The remaining two groups were similarly injected with CPA and CARM (10 mg/kg). Control animals were injected with nonpyrogenic sterile water or saline solution. After 12 and 24 hours, the animals were killed with an overdose of chloral hydrate, and bone marrow smears were prepared for determining chromosomal damage in polychromatic erythrocytes (PCEs) by a micronucleus test. In protocol 2, CPA and CARM were injected, and 15 minutes later, bolus injections of diatrizoate, ioxaglate and iohexol were given through the same route. Both ionic and nonionic CM induced significant numbers of micronuclei in PCEs (P less than .05). CPA caused a severe cytogenetic effect, whereas CARM did not produce a significant number of micronuclei in PCEs compared with control. In protocol 2 experiments, antagonism with CPA and synergism with CARM was demonstrable. Clinical implication of the cytogenetic interactions between CM and antineoplastic drugs remains to be established.     

Intravenous contrast material administration at helical 16-detector row CT coronary angiography: effect of iodine concentration on vascular attenuation

The institutional review board approved this study, and all patients gave written informed consent. One hundred twenty-five patients scheduled to undergo retrospectively electrocardiographically gated 16-detector row computed tomographic coronary angiography were prospectively randomized into the following five groups with respect to the intravenous administration of a 140-mL bolus of contrast material at 4 mL/sec: group 1 (iohexol [300 mg of iodine per milliliter]), group 2 (iodixanol [320 mg I/mL]), group 3 (iohexol [350 mg I/mL]), group 4 (iomeprol [350 mg I/mL]), and group 5 (iomeprol [400 mg I/mL]). Attenuation was measured in the descending aorta and coronary arteries. One-way analysis of variance was used to compare groups. Mean attenuation values in the descending aorta were significantly (P < .05) lower in group 1 and higher in group 5 compared with the mean values in the other three groups. The same pattern was observed in the coronary arteries. Contrast materials with higher iodine concentrations yield significantly higher attenuation in the descending aorta and coronary arteries.     

A comparison of blood-brain barrier disruption by intracarotid iohexol and iodixanol in the rabbit

A rabbit model was used to compare the effect on the blood-brain barrier of the intracarotid injection of two new contrast media: iohexol, a nonionic monomer, and iodixanol, a nonionic dimer. It was hypothesized that the low osmolality of iodixanol (272 mOsm/kg at 300 mgl/ml) would cause less disruption of the blood-brain barrier than the relatively higher osmolality of iohexol (690 mOsm/kg at 300 mgl/ml). The degree of blood-brain barrier disruption was assessed qualitatively, by observing the degree of cortical staining with Evans' Blue dye, and quantitatively, by calculating the difference in uptake of 99mTc-pertechnetate between injected and noninjected hemispheres. Statistical analysis of the results showed that both iodixanol and iohexol had a significantly greater effect on blood-brain barrier disruption than did isotonic saline (0.005 greater than p greater than .001), but that the effect of iodixanol was not significantly different from that of iohexol with respect to either Evans' Blue staining (p greater than .05) or pertechnetate uptake (.75 less than p less than .90). Thus, the low-osmolality iodixanol has no significant advantage over iohexol in terms of blood-brain barrier disruption after experimental carotid angiography.     

Urine profiles and kidney histology following intravenous diatrizoate and iohexol in the degeneration phase of gentamicin nephropathy in rats. Effects on urine and serum profiles.

Urine chemical profiles were followed for three or nine days after intravenous injection of diatrizoate, iohexol, or saline in 30 rats, where a tubulointerstitial nephropathy was induced by gentamicin given over an eight-day period. Another ten rats injected with saline served as controls. Compared to injection of saline, both iohexol and diatrizoate induced dysfunction. The excretion of the cytoplasmic enzyme lactate dehydrogenase was significantly greater following iohexol than following diatrizoate. No significant differences between the two media were shown by the various serum components examined. Among the gentamicin-treated rats, light microscopy showed prolonged occurrence of tubular necrosis and a more intensive round cell infiltration following iohexol than following diatrizoate and saline. Both contrast media induced further temporary renal dysfunction in rats with gentamicin nephropathy; iohexol induced more morphologic changes than diatrizoate.     

Opiate involvement in contrast media-induced blood pressure changes

The intravenous administration of contrast media (CM) often alters blood pressure (BP). Osmolality plays a role, but the magnitude and even direction of change varies under similar (osmotic) conditions, indicating the involvement of other mechanisms. Male Wistar rats, anesthetized with pentobarbital, received sodium/meglumine diatrizoate, iohexol, or normal saline, 4 ml/kg, via a tail vein, while blood pressure was recorded continuously. Additional groups were pretreated with the opiate antagonist, naloxone (1 mg/kg, IV), or with an equal volume of normal saline 5 minutes prior to the diatrizoate injection. Comparisons of BP change were made with the Student's t-test. Diatrizoate caused a significant (P less than .0002) increase in BP relative to the saline control group, iohexol did not. Thus, the increase with diatrizoate was significantly greater than with iohexol (P less than .00006). Neither the saline nor naloxone pretreatment altered BP significantly. Saline pretreatment did not alter the significant increase in BP produced by the diatrizoate. However, the diatrizoate-induced increase in BP was prevented by the naloxone pretreatment and was significantly less than after the saline pretreatment (P less than .0001). Based on these and previous results, the authors hypothesize that release of endogenous opioids may play a role in BP changes caused by intravenous CM and that significant CM-induced changes may be prevented pharmacologically with the selective opiate blocker, naloxone.     

Comparison of vascular opacification after bolus injection of iodixanol-320 iohexol-350.

RATIONALE AND OBJECTIVES. The vascular opacification characteristics of a new nonionic, dimeric contrast agent, iodixanol, have been compared with a nonionic, monomeric agent, iohexol, using ultrafast computed tomography (UFCT). METHODS. In 10 experiments with mongrel dogs, the contrast agents were alternately injected into the animal's left atrium, and UFCT images were obtained at four cross-sectional levels through the carotid arteries. Time-density curves were then obtained for each carotid artery and each agent. The peak height and area under the curves were compared for each agent. RESULTS. Iohexol provided significantly (P < or = .05) greater opacification, determined by paired Student's t tests. CONCLUSION. This result was predicted from the greater iodine concentration of iohexol (350 mg/mL) compared with iodixanol (320 mg/mL); the difference was greater than expected based on iodine content alone.     

Nephrotoxicity of cyclosporin A and contrast media. A comparison between diatrizoate and iohexol in rats

Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 22 h or 8 days after intravenous injection of diatrizoate, iohexol or saline in 30 adult Wistar rats in which nephrotoxicity was induced by daily peroral administration of 25 mg/kg body weight cyclosporin A over a 14-day period. Another 10 rats which had the vehicle of the cyclosporin A solution (placebo) and saline injected intravenously served as controls. The effect of iohexol and saline on the albumin excretion was similar, whereas diatrizoate increased it significantly. Both contrast media caused significantly increased excretion of all three enzymes. The contrast media had no effect on the excretion of glucose and sodium. Except for the fact that the excretion of NAG was significantly higher following iohexol than following diatrizoate 24 to 46 h after injection no significant differences between the two media were found from 24 h after injection among the rats given cyclosporin A. No contrast medium related changes were found by light microscopy of the kidneys. Neither iohexol nor diatrizoate potentiate acute cyclosporin A nephrotoxicity.     

Effects of intravenous injection of diatrizoate, iohexol or ioxilan on renal size, urine profiles and blood profiles in the rabbit

Diatrizoate, iohexol or ioxilan were injected intravenously in 18 rabbits. The contrast medium passage through the kidneys was recorded on digital subtraction images for the first 50 s followed by 100 mm exposures up to 15 min after injection. The renal area was measured planimetrically. Urine profiles (glucose, phosphate, LDH, GGT, NAG), blood profiles (potassium, urea) and the relative clearance of albumin and sodium were followed for 5 days and compared with a control group injected with saline. All kidneys were examined by light and immunofluorescence microscopy. All three contrast media produced excellent arteriograms and urograms. The three different contrast media caused a rapid increase of the kidney area within the first minute, reaching an average maximum of 10 to 12 per cent after 5 min, followed by a gradual decline. Contrary to expectations the increase in renal area was similar for all three contrast media, so hyperosmolality is no likely explanation of this phenomenon. None of the contrast agents caused significant changes in any of the profile components with one exception: the GGT excretion was significantly elevated during the first 24 h after diatrizoate administration as compared with the effect of saline. Light and immunofluorescence microscopy revealed no differences.     

Efficacy of oral supplemental hydration for the prevention of contrast-induced nephropathy in rats

Purpose

To compare oral rehydration solution (ORS) with saline infusion for preventing contrast-induced nephropathy (CIN) in a rat model.

Materials and methods

Adult male Sprague–Dawley rats (310–360 g) received intravenous indomethacin (10 mg/kg), N ^G-nitro-l-arginine methyl ester (10 mg/kg), and iohexol (10 mL/kg) to induce acute contrast-induced renal injury (CIN group); control rats received saline only. For hydration, rats received either continuous infusion (20 mL/kg/h) of saline or three oral doses (20 mL/kg each) of ORS. Acute renal injury was evaluated by assaying urine collected for 24 h beginning 2 h before the contrast injection, evaluating blood taken 22 h after the contrast injection, and examining the kidneys histopathologically.

Results

Hydration with saline prevented only the contrast-induced increase in plasma creatinine, whereas ORS prevented deleterious changes in plasma creatinine, blood urea nitrogen, and creatinine clearance as well as in urinary protein, albumin, and N-acetyl-d-glucosaminidase concentrations. Histopathologic changes noted in the CIN group were diminished in both saline and ORS groups.

Conclusion

Both intravenous saline administration and oral hydration with ORS decreased the severity of CIN. Hydration with ORS was comparable to intravenous saline infusion in preventing CIN-associated abnormalities.

     

Pretreatment with steroids before intravenous injection of diatrizoate or iohexol. Effects on urine and serum profiles.

The effects on urine and serum profiles of intravenous injection of diatrizoate, iohexol, or saline were studied in male rats pretreated with steroids or saline. Using urinary albumin, glucose, sodium, and the enzymes lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), and N-acetyl-beta-D-glucosaminidase (NAG) as markers of glomerular and tubular function, it was found that diatrizoate caused temporary glomerular and tubular dysfunction; the effect was independent of the kind of pretreatment. Iohexol did not cause increased glomerular permeability in steroid- and saline-pretreated rats. When used following saline, iohexol induced increased excretion of three tubular components, whereas iohexol plus steroids caused increased excretion of all five tubular components. The dysfunctional effect of iohexol plus steroids was less than that of diatrizoate plus steroids. The serum components revealed no abnormalities induced by either contrast media or methylprednisolone. Pretreatment with steroids has no effect on the glomerular or tubular dysfunctional effect of diatrizoate, whereas it worsens the temporary tubular dysfunctional effect of iohexol in rats.