Effect of radiologic contrast media on cell volume regulation in rabbit proximal renal tubules

RATIONALE AND OBJECTIVES: Most radiographic contrast media are hyperosmotic and able to shrink cells with which they are in contact. The authors studied cell volume control in rabbit proximal renal tubules after incubation with three contrast media: iohexol, ioxaglate, and iodixanol. MATERIALS AND METHODS: Proximal renal tubules were isolated from rabbit kidneys. The tubules were exposed to Ringer solutions containing 5% vol/vol iohexol (final osmolality, 330 mOsm), ioxaglate (323 mOsm), iodixanol (305 mOsm), or mannitol (control solutions with identical osmolalities), and tubule volumes were monitored. After 2 hours of incubation, the tubules were stimulated with a hyposmotic Ringer solution (165 mOsm). Three groups of 10 experiments were performed. RESULTS: All solutions induced cell shrinkage (8.3%+/-3.8 [standard error] to 15.4%+/-0.5), which was completely or partly reversible in most experiments (volume increase, 44.8%+/-14.7 to 149.9%+/-107.3) but not those with iohexol and iodixanol. With exposure to the hyposmotic solution, the cells swelled by 11.0%+/-1.8 to 39.7%+/-4.8. In general, the tubules that had been exposed to the most hyperosmotic solution swelled the most. Those exposed to contrast media showed less swelling than the mannitol-exposed controls. In all control experiments, the cells exhibited a gradual shrinkage (43.6%+/-28.5 to 87.0%+/-13). This regulatory response was partly inhibited in tubules exposed to iohexol (39.9%+/-15.8 shrinkage) or iodixanol (8.9%+/-15.8) and completely inhibited in those exposed to ioxaglate. Iohexol and ioxaglate exposure also led to a decrease in water permeability. CONCLUSION: Exposure to hyperosmotic contrast medium tends to induce prolonged cell shrinkage, decrease the water permeability of the cellular plasma membranes, and compromise the ability to regulate cellular volume. These changes seem to reflect both the hyperosmolality of the solutions and their inherent chemical properties.     

Effect of radiologic contrast material on cell volume regulation in proximal renal tubules from trout (Salmo trutta)

RATIONALE AND OBJECTIVES: Most radiographic contrast media (CM) are hyperosmotic and pose an osmotic threat to cells they are in contact with. To study these effects at the cellular level, cell volume regulatory mechanisms were observed in proximal renal tubules following exposure to the CM iohexol, ioxaglate, and iodixanol. MATERIALS AND METHODS: Isolated renal tubules from trout (Salmo trutta) were exposed to 5% vol/vol iohexol (326 mOsm), ioxaglate (314 mOsm), or iodixanol (300 mOsm) or mannitol (to achieve the same osmolalities), and cell volume changes were observed videometrically. RESULTS: Iohexol and ioxaglate solutions induced a rapid shrinkage (12%-13%) not followed by cell volume regulation. Without CM (same osmolality), the cells shrank 11% but then showed a 77%-88% volume recovery. This reswelling was inhibited by 55% with the Na+, K+, Cl- symporter inhibitor bumetanide (50 micromol/L). Iodixanol did not significantly affect cell volume. Tubules preincubated with CM or mannitol were then stimulated with a hypoosmotic Ringer solution (160 mOsm) resulting in a 26%-36% cellular volume increase. Compared with results of experiments without mannitol and CM, preexposure to iohexol or ioxaglate almost completely inhibited the expected regulatory shrinkage phase, while previous exposure to hyperosmotic solutions with mannitol reduced the shrinkage response by 40%-53%. CONCLUSION: In this system, the hyperosmotic iohexol and ioxaglate cause cell shrinkage followed by an impaired cell volume regulatory response. Exposure to these two CM also inhibits cell volume regulation on hypoosmotic stimulation. The isosmotic iodixanol has no such effects. These changes appear to some extent to be a result of the CM's degree of hyperosmolality, but this property alone does not explain these findings.     

In vivo comparative antithrombotic effects of ioxaglate and iohexol and interaction with the platelet antiaggregant clopidogrel

RATIONALE AND OBJECTIVES: Experiments were designed to (1) compare the effects of iodinated contrast media (CM) on a rat model of arterial thrombosis, (2) evaluate which element of the ioxaglate solution supports its antithrombotic activity, and (3) investigate the interaction of ionic and non-ionic CM with the antiplatelet agent clopidogrel. MATERIALS AND METHODS: Carotid thrombosis was induced in rats by extravascular application of a filter paper soaked in FeCl3 (35% vol/wt), proximal to an ultrasonic flow probe. (1) The antithrombotic potential of low-osmolar ionic (ioxaglate Na/meglumine) or nonionic contrast media (iohexol and iodixanol) (all 1600 mg iodine/kg, IV) was assessed by measuring the time to occlusion (TTO) of the carotid artery and the thrombus weight (TW). (2) Isotonic saline and iso-osmolar (280 mOsm/kg) and hyperosmolar (560 mOsm/kg) solutions of meglumine hydrochloride, meglumine ioxaglate (560 mOsm/kg), sodium ioxaglate (600 mOsm/kg) and sodium and meglumine ioxaglate (commercial solution) were tested under similar conditions. (3) Interaction with clopidogrel was tested by injecting lower dose of CM (960 mg iodine/kg) 2 hours after clopidogrel (2 mg/kg per os). RESULTS: (1) Ioxaglate prolonged TTO when compared with saline (30.0 +/- 1.1 minute vs. 19.6 +/- 2.4 minutes, P< 0.001), whereas iohexol had no effect (21.3 +/- 1.3 minutes). Ioxaglate's effect was associated with a reduction in TW with ioxaglate versus saline (2.6 +/- 0.4 mg and 4.7 +/- 0.7 mg, respectively, P< 0.05) whereas TW remained unchanged in the iohexol group (4.2 +/- 0.4 mg). The nonionic dimer iodixanol induced a direct vasoconstrictor effect on the carotid artery and was consequently excluded from the study. (2) Neither iso-osmolar nor hyperosmolar solutions of meglumine had any effect on TTO whereas both sodium and meglumine salts of ioxaglic acid prolonged TTO, suggesting that the antithrombotic effect of ioxaglate is mediated by the ioxaglic acid moiety alone as neither meglumine, osmolality or sodium played a significant role. (3) A synergistic effect on TTO was found when ioxaglate was associated with clopidogrel whereas no such effect was observed with iohexol. CONCLUSIONS: These data show a greater in vivo antithrombotic potential for the ionic contrast medium ioxaglate than for the non-ionic contrast medium iohexol and, for the first time, a synergistic effect between a contrast medium and a platelet antiaggregant drug in vivo.     

Comparative effects of ionic and nonionic iodinated low-osmolar contrast media on platelet function with the PFA-100 (platelet function analyzer)

RATIONALE AND OBJECTIVES: This study was designed to (1) compare the effects of ionic (ioxaglate) and nonionic (iodixanol and iohexol) iodinated low-osmolar contrast media (CM) on platelet function in human whole blood by using the new PFA-100trade mark, a "platelet function analyzer"; (2) determine the animal species closest to human with regard to platelet reactivity to CM; and (3) evaluate which element of the ioxaglate solution supports this activity. METHODS: For all studies, platelet adhesion and aggregation were measured using the PFA-100trade mark system with adenosine diphosphate-primed collagen membrane cartridges. Results are shown as the membrane closure time (MCT; the longer the MCT, the greater the antiaggregatory effect) and given as medians. Citrated whole-blood samples from six healthy volunteers were mixed for 1 minute with a 10% (vol/vol) solution of ioxaglate, iodixanol, or iohexol or their respective ionic and nonionic controls (isotonic saline and mannitol). The test solution/control solution ratio for the MCT was calculated for the blood of humans, guinea pigs, rabbits, dogs, and rats. Isotonic saline and iso-osmolar (280 mOsm/kg) and hyperosmolar (560 mOsm/kg) solutions of meglumine hydrochloride, meglumine ioxaglate (560 mOsm/kg), and sodium ioxaglate (600 mOsm/kg) were tested under similar conditions. RESULTS: All three CM caused significant prolongation of MCT when compared with their respective controls (ioxaglate: 300 seconds, ie, "no closure" on the PFA-100trade mark system; iodixanol: 179 seconds; iohexol: 171 seconds; saline: 115 seconds; mannitol: 118 seconds). The antiplatelet effect of ioxaglate was higher than that of iodixanol and iohexol (P < 0.05). The animal species tested did not differ significantly from the human species with regard to an effect of their blood on MCT. Both ioxaglic acid salts caused a higher prolongation of MCT when compared with saline (sodium salt: 259 seconds; meglumine salt: 212 seconds; P < 0.05 vs. saline) but not versus the ioxaglate commercial solution. Conversely, both iso- and hyperosmolar solutions of meglumine hydrochloride (108 and 128 seconds, respectively) did not lengthen MCT versus saline, but their MCTs were shorter than that of the commercial solution of ioxaglate (P < 0.05). CONCLUSIONS: The ionic CM ioxaglate displayed a greater antiaggregatory effect on human platelets than did both iso-osmolar (iodixanol) and hyperosmolar (iohexol) nonionic CM. This effect seems to be linked to the ioxaglic moiety, because neither osmolality nor sodium or meglumine appeared to play a significant role.     

Granulocyte adherence is inhibited by radiographic contrast media in vitro.

Different amounts of diatrizoate, ioxaglate, iohexol, iodixanol, NaCl 1,000 mOsm/kg, mannitol 1,098 mOsm/kg, and meglumine (meglumine concentrations corresponding to the content in the diatrizoate solutions) were added to either whole blood or a suspension of granulocytes in autologous plasma, and the adherence to nylon fibers was determined. At high concentrations all the investigated contrast media (CM) inhibited granulocyte adherence. The degree of inhibition was significantly greater when the ionic CM diatrizoate and ioxaglate were used, as compared with the nonionic media. Meglumine solutions at high concentrations also inhibited adherence but significantly less than diatrizoate solutions containing the same amount of meglumine. Diatrizoate showed the greatest inhibitory effect on granulocyte adherence, and significant inhibition could be detected even with a 1.25% solution.     

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.     

Left ventricular systolic and diastolic function during coronary arteriography before and after acute left ventricular failure in dogs. A comparison between iodixanol, iohexol and ioxaglate

The hemodynamic side effects of intracoronary injection of low osmolality contrast media were studied in anesthetised dogs, both with and without left ventricular (LV) failure. LV failure was induced by microembolization of the area supplied by the left main coronary artery. LV pressure and volume, aortic pressure, and cardiac output were recorded. 6 ml iodixanol 320 mg I/ml containing 20 mmol Na+/l, a new non-ionic dimer, was compared to iohexol and ioxaglate. Iodixanol induced small systolic alterations both before and after LV failure. Iohexol increased LV inotropy while ioxaglate depressed myocardial function. Before failure iodixanol and ioxaglate impaired isovolumic relaxation, but early diastolic filling was not reduced. After failure the relaxation process was not affected, but ioxaglate reduced early diastolic filling. Ioxaglate also increased LV end-diastolic pressure and volume more than the non-ionic contrast media. In conclusion, iodixanol induced only small changes in systolic and diastolic function. Iodixanol should therefore be hemodynamically well tolerated during coronary arteriography, and also in acute ischemic heart failure.     

Blood pool and liver enhancement in CT with liposomal lodixanol: comparison with lohexol

RATIONALE AND OBJECTIVES: The authors compared the time course and blood pool and hepatic enhancement of three different doses of liposomal iodixanol with those of iohexol. MATERIALS AND METHODS: A liposomal iodixanol formulation was prepared with 200 mg of iodine per milliliter total and 80 mg of iodine per milliliter encapsulated. Twelve normal New Zealand white rabbits divided into four groups received 75-, 100-, or 150-mg encapsulated iodine per kilogram doses of liposomal iodixanol or 2 mL/kg iohexol with 300 mg of iodine per milliliter. A liver section was scanned with serial computed tomography (CT) before the injection, immediately afterward, and at 1-minute intervals for 10 minutes. Region-of-interest measurements of the aorta and liver were plotted at each time point, and contrast enhancement was plotted as a function of time and iodine dose. RESULTS: All liposomal iodixanol doses produced greater liver enhancement than iohexol. Results were significant (P < .05) for 100 mg and 150 mg iodine per kilogram dose groups at time points beyond 2 minutes. Peak hepatic enhancement (change in attenuation) was 54.9 HU +/- 7.6 with iohexol, compared with 59.6 HU +/- 6.1, 73.3 HU +/- 3.6, and 104.1 HU +/- 8.8 for 75, 100, and 150 mg encapsulated iodine per kilogram doses, respectively. Hepatic enhancement increased rapidly after injection of liposomal iodixanol, plateauing 2-3 minutes later. Blood pool enhancement decreased rapidly. Steady-state liver enhancement with liposomal iodixanol increased linearly with dose. Aortic enhancement was greater with iohexol. CONCLUSION: Liposomal iodixanol yielded greater hepatic enhancement at lower total iodine doses than iohexol. Although liver enhancement occurred rapidly after injection, blood pool enhancement was brief.     

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.     

Protective Effects of Repetitive Injections of Radiographic Contrast Media on the Subsequent Tolerance to Ischemia in the Isolated Rat Heart

Purpose: Despite detailed knowledge of the effects of X-ray contrast media on cardiac function, no studies have examined the effect of contrast media injections on the subsequent tolerance to ischemia in the heart. Methods: Isolated perfused rat hearts were exposed to repetitive injections of iohexol, iodixanol, or ioxaglate before 30 min of global ischemia and 120 min of reperfusion. These groups were compared with control (no pretreatment) and ischemic preconditioning known to reduce infarct size. Physiologic variables and infarct size were measured Results: Pretreatment with iodixanol reduced infarct size significantly compared with control and thus afforded protection against ischemia. Injections with iohexol and ioxaglate reduced infarct size, although not significantly, compared with control. Conclusion: Pretreatment of the isolated rat heart with commonly used contrast media enhances the cardiac tolerance to subsequent ischemia. The mechanism behind this protective effect could not be determined, but could involve stretching of the heart and/or generation of nitric oxide.     

The effect of low-osmolar ionic and nonionic contrast media on human blood viscosity, erythrocyte morphology, and aggregation behavior

The effects of three low-osmolar radiographic contrast media (CM)--two nonionic (iohexol, iopamidol) and one ionic (ioxaglate)--on red blood cell (RBC) morphology and aggregation behavior, as well as on blood and plasma viscosity, have been studied. Blood taken from normal, healthy individuals and from patients with uremia was investigated. The authors controlled for the effects of dilution, ionic and nonionic hyperosomolality, and specific chemotoxicity. With ioxaglate, the normal biconcave RBC morphology was fairly well maintained. Iohexol produced a mixture of more-or-less normal cells and echinocytes, while iopamidol yielded only echinocytes. Irregular RBC aggregates have been frequently associated with the presence of echinocyte morphology. In the case of ioxaglate, the capacity of normal blood for rouleaux formation was preserved. This appeared to be compatible with an only moderate decrease in low shear viscosity values. In comparison to the normal control group, RBCs from patients with uremia were clearly more sensitive for hyperosmolar stress. It can be concluded that, in contrast to the nonionic CM, the ionic dimeric compound ioxaglate seems to protect human RBCs against hyperosmolar stress by a mechanism unknown at the present.     

Morphologic degeneration of human microvascular endothelial cells induced by iodinated contrast media

RATIONALE AND OBJECTIVES: The purpose of this study was to characterize the adverse effects of iohexol and ioxaglate on human microvascular endothelial cells, which may result in phlebitis, pain, and thrombosis. MATERIALS AND METHODS: The degree of morphologic degeneration and of lactate dehydrogenase (LDH) efflux into the extracellular medium (as an index of cell viability) were determined in endothelial cell culture exposed for 10, 30, or 60 minutes to ioxaglate or iohexol (ionic and nonionic contrast media, respectively) at iodine concentrations of 100 or 150 mg/mL. RESULTS: Ioxaglate induced concentration- and time-dependent morphologic degeneration, including shrinkage and loss of the cell tip in 20%-80% of endothelial cells; iohexol did not. After 60 minutes of exposure, ioxaglate at the higher concentration (150 mg iodine per milliliter) significantly increased the LDH signal (ie, the percentage of LDH released), to 20%. CONCLUSION: The present findings demonstrate that ioxaglate but not iohexol causes morphologic degeneration of the microvascular endothelial cells. This direct cytotoxic action of ioxaglate probably causes endothelial cell dysfunction, closely associated with the occurrence of phlebitis, pain, and thrombosis.     

Sodium addition to nonionic contrast media. Effects on cardiac monophasic action potentials and hemodynamics in a dog model

In order to study the electrophysiologic and hemodynamic effects of sodium addition to low-osmolality contrast media during coronary arteriography, eight dogs with surgically opened thoraces were studied. Epicardial monophasic action potentials (MAP) were recorded from the contrast perfused area, using suction electrodes. Six milliliters of iohexol, iohexol with addition of 20 to 80 mmol/L Na+ and ioxaglate, were selectively administered into the left coronary artery. Only minor hemodynamic alterations occurred with the iohexol solutions, whereas ioxaglate decreased left ventricular (LV) inotropy and pressures initially. Iohexol and iohexol containing less than 40 mmol/L Na+ did not change MAP duration significantly. The addition of 80 mmol/L Na+ to iohexol lengthened MAP duration at 25%, 50%, and 90% repolarization by 14 +/- 2, 18 +/- 3, and 18 +/- 5 mseconds, respectively. Ioxaglate lengthened MAP duration by 14 +/- 3, 17 +/- 3, and 26 +/- 8 mseconds, respectively. Thus, during coronary arteriography in dogs, iohexol with sodium added, like ioxaglate, induced regional electrophysiologic changes in the contrast-perfused area of the myocardium, while sodium-free iohexol did not.     

Viscosity of some contemporary contrast media before and after mixing with whole blood.

The viscosity of 7 contrast media was measured using a rotational viscometer. When solutions with similar iodine concentrations were compared, the highest viscosities were found for the nonionic dimers iodixanol and iotrolan, the lowest for diatrizoate, iopamidol, and iopromide, and intermediate values for iohexol and ioxaglate. The viscosity of iohexol and ioxaglate was found to vary linearly with temperature and quadratically with concentration. Whole-blood viscosity was measured for 5 subjects at high and low shear rates before and after mixing with contrast media in various proportions. Low-shear viscosity was found to decrease and high-shear viscosity to increase with contrast medium concentration. It is concluded that the contrast media currently used may affect blood rheology less than previous agents, despite their higher viscosity.     

Phagocytic properties of granulocytes after intravenous injection of ioxaglate or iohexol.

To evaluate the influence of radiographic contrast media (CM) on human granulocytes, the ability of these cells to ingest latex particles after intravenous injection of ioxaglate and iohexol was investigated. Both CM inhibited the phagocytic properties of granulocytes; the inhibition was the most pronounced immediately after the injection, but inhibition was also observed 60 min after injection of ioxaglate. The inhibition 1 and 5 min after injection of CM was more pronounced after injection of ioxaglate than after injection of iohexol. However, this difference between the 2 CM was not significant. Significant inhibition of phagocytosis was found for mannitol solutions with osmolalities higher than 369 mOsm/l. Significant inhibition of phagocytosis was observed when granulocytes were isolated with either Hypaque/Ficoll or Percoll gradient centrifugation and then incubated with diatrizoate. Thus the ability of granulocytes to phagocytize latex particles was inhibited after i.v. injection of 50 ml ioxaglate or iohexol. Part of this inhibition may be due to hyperosmolality.     

Effects of two dimeric iodinated contrast media on renal medullary blood perfusion and oxygenation in dogs

RATIONALE AND OBJECTIVES: To compare the effects of two iodinated contrast media, iodixanol and ioxaglate, on outer medullary blood flow (MBF) and oxygen tension (MPO(2)) in the dog kidney. METHODS: Iodixanol and ioxaglate were injected selectively into the renal artery (320 mgI/kg) of anesthetized Beagle dogs. MBF and MPO(2) were measured with a laser-Doppler probe and an oxygen-sensing microelectrode implanted in the outer medulla. Urine samples were collected for viscosity and osmolality measurements. RESULTS: Both contrast media produced a moderate decrease in MBF and MPO(2). The hypoperfusion and hypoxia lasted significantly longer with iodixanol than with ioxaglate. Theophylline, an adenosine receptor antagonist, partially prevented iodixanol-induced hypoxia. Urine viscosity was dramatically increased by iodixanol but not by ioxaglate. Urine osmolality did not differ significantly between groups. CONCLUSION: Iodixanol produced a more sustained medullary hypoxia than ioxaglate when injected selectively into the dog renal artery. This may lead to hypoxic cellular damage and subsequent impairment of kidney functions.     

The effects of angiographic contrast media on the aggregation and morphology of red cells in vitro

The effects of four angiographic contrast media on the aggregation and morphology of human red cells in vitro, using microscopic observations were studied. The media included an ionic contrast medium, sodium meglumine amidotrizoate (amidotrizoate); non-ionic low-osmolal contrast media, iopamidol and iohexol; and an ionic low-osmolal contrast medium, sodium meglumine ioxaglate (ioxaglate). Strong, large aggregates formed in the control blood, without media, where aggregation of red cells was inhibited by contrast media mixed with the blood in a ratio of 2:1. Almost no aggregates were observed for amidotrizoate, an ionic contrast medium, while there were a few rouleaux formed in the presence of ioxaglate. Nearly all of the red cells aggregated in the presence of iopamidol and iohexol; iohexol produced the greater aggregation of the two. Besides rouleaux, irregular aggregates were formed with iohexol. When the contrast media were mixed with blood in a ratio of 1:2, their inhibitory effects on aggregation declined. These results clearly indicate that contrast media inhibit the in vitro aggregation of red cells, and ionic-contrast media produced more potent inhibitory effects than non-ionic media. With added NaCl and meglumine, iohexol did not induce red cell aggregation. This suggests that ionic-contrast media have greater inhibitory effects on aggregation than non-ionic media, a result of their ionic properties. Red cells were morphologically quite normal in the presence of ioxaglate, where most red cells were crenated in the presence of iopamidol and iohexol, and shrank in the presence of amidotrizoate. In the presence of iopamidol and iohexol with the osmolality adjusted to that of a saline solution, both normal red cells and crenation were observed. This suggests that non-ionic contrast media may directly effect morphological changes in red blood cells. These results revealed that ioxaglate, an ionic contrast medium, was the best in vitro medium, to prevent aggregation of red cells and crenation deformity of erythrocytes.     

Optimal contrast agents for vascular imaging on computed tomography: iodixanol versus iohexol

RATIONALE AND OBJECTIVES: Dimeric nonionic iodinated contrast has a lower osmolality than monomeric nonionic iodinated contrast but is available at lower iodine concentrations. Less dilution of intravascular fluid by influx from the extravascular space is proposed to occur with decreasing osmolality. The purpose of this study was to determine if a dimeric nonionic iso-osmolar contrast agent (iodixanol) gives equal vascular enhancement compared with a monomeric nonionic hyperosmolar contrast agent (iohexol). MATERIALS AND METHODS: A dynamic single-level computed tomography (CT) scan was performed of the abdominal aorta of 12 sedated rabbits using a four-row multidetector CT scanner following injection of 1.5 mL contrast/kg body weight at 2 mL/sec. The rabbits were injected with the dimeric contrast agent iodixanol (Visipaque 320; Amersham Health) or the monomeric contrast agent iohexol (Omnipaque 350; Amersham Health). The order of the type of contrast media injected was randomized for each rabbit, and the interval between injections was 2 weeks. Using the 2.5-mm detectors, four contiguous 3-mm contrast-enhanced scans were obtained at a single level every 5 seconds for 120 seconds (total of 24 scans) with a kVp of 120, mA.s of 110, field of view of 106 mm, and soft tissue reconstruction algorithm. A single level was chosen to measure the attenuation of the abdominal aorta at 5-second intervals. The mean attenuation and standard deviation values were recorded for the whole aorta, for the central half of the vessel, and for the peripheral half of the vessel. A log-log transformation of the data was performed and regression analysis was done on the outcomes of interest (e.g., mean, standard deviation) on time for each region. RESULTS: There was no statistically significant difference in mean attenuation for the whole aorta for iodixanol and iohexol (P = .918) even though the iodine content was 9.3% less with the dimeric iodixanol. The time-attenuation curve of iodixanol paralleled that of iohexol for all time points. The mean attenuation values of the central half of the aorta (P = .354) and peripheral half of the aorta (P = .758) were also not statistically different for the two contrast agents. CONCLUSION: The vascular attenuation provided by a 9.3% lower iodine concentration of iso-osmolar iodixanol is equal to that given by hyperosmolar iohexol. This suggests that there is less intravascular dilution of iso-osmolar contrast. The enhancement across the cross section of the vessel is also similar for both contrast agents. This suggests the vascular studies with iodixanol and iohexol are of equal quality even when a lower dose of iodine is given with iodixanol. It is relevant for patients with borderline or diminished renal function in whom less volume of contrast may be administered.     

Pain in peripheral arteriography: an assessment of conventional versus ionic and non-ionic low-osmolality contrast agents

Two low-osmolality contrast agents, ioxaglate meglumine/sodium and iohexol were compared with diatrizoate meglumine/sodium in a controlled double blind study of 126 patients undergoing arteriography for peripheral vascular disease to determine which caused the least pain. Discomfort was assessed by means of a visual analog scale rating pain from 0 to 100. Average values for pain were 39 +/- 27 for diatrizoate, 14 +/- 15 for ioxaglate and 21 +/- 22 for iohexol. We found that both low-osmolality agents caused significantly less pain in peripheral arteriography than the traditional agent. The p values were p less than 0.0005 for ioxaglate and p less than 0.005 for iohexol versus diatrizoate. In addition, ioxaglate was found to cause significantly less pain than iohexol (p less than 0.05) in this patient group.     

Cutaneous ulceration due to contrast extravasation. Experimental assessment of injury and potential antidotes

Severe cutaneous ulceration may occur as a result of contrast media extravasation. We established a definitive animal model for assessing the cutaneous toxicity of commonly employed agents and used this model to evaluate possible antidotes to the effects of contrast media extravasation. The contrast agents studied were: meglumine/sodium diatrizoate 76%, meglumine iothalamate 60% and 43%, meglumine/sodium ioxaglate 60%, iohexol 350, and iopamidol 370, in varying volumes and osmolalities. Hypertonic saline (950 and 1900 mOsm/kg) also was injected. Agents were injected intradermally into BALB/c mice. The higher osmolality agents produced dose-dependent skin ulcerations. The lower osmolality agents failed to produce any skin lesions after the same volume doses. Hypertonic saline produced skin toxicity in a dose-dependent fashion similar to hyperosmolar contrast agents. Three antidotes were tested: hyaluronidase, topical heat, and topical cold. Hyaluronidase significantly reduced skin toxicity when injected immediately following contrast injection. Cold also significantly reduced skin toxicity, while heat caused no improvement.