Early effect of gadopentetate and iodinated contrast media on rabbit kidneys.

RATIONALE AND OBJECTIVES: The authors compared the physiologic and nephrotoxic effects of the magnetic resonance imaging contrast medium gadopentetate with two conventional radiographic contrast media. METHODS: Rabbits were injected intravenously with one of the following solutions: 1) gadopentetate (0.1 M); 2) iohexol (300 mg I/mL); 3) metrizoate (300 mg I/mL); and 4) NaCl (0.9%). Blood samples were taken before and 5, 15, 45, 90, and 180 minutes after injection of the solutions and were analyzed for creatinine, aldosterone, and contrast media levels. Urine was sampled before and 1, 2.5, and 5 hours after injection of the solutions, and creatinine, leucine amino peptidase (LAP), alkaline phosphatase (ALP), gamma glutaryl transferase (GGT), and N-acetyl beta-D-glucosaminidase (NAG) activities were quantified. RESULTS: Contrast media clearance was similar for gadopentetate, iohexol, and metrizoate. Plasma aldosterone was significantly higher in the two groups injected with iodinated contrast agents compared with the gadopentetate and saline groups in the 3-hour samples. During the 5 hours after injection, the excretion of brushborder enzymes LAP, ALP, and gamma GT was significantly higher for all contrast media compared with pre-contrast values and 0.9% NaCl controls. NAG, a lysosomal enzyme from tubular cells, showed a significant increase compared with pre-contrast values for all contrast media. CONCLUSIONS: Intravenous injection of gadopentetate in rabbits showed nephrotoxicity of the same order as that of conventional iodinated contrast media.

Systemic, pulmonary and renal haemodynamic effects of large intravenous doses of high and low osmolar contrast media. An investigation in the pig of ratio 1.5 and ratio 3 media.

The central, peripheral and renal haemodynamic effects of intravenous infusion (1 ml/s) of large doses (4 ml/kg body weight) of non-ionic (iohexol) and ionic (metrizoate and ioxaglate) contrast media were studied in 24 anaesthetized pigs. All contrast media showed marked haemodynamic effects with an increase of mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary occlusion pressure, cardiac output and stroke volume. The response of the pulmonary circulation to contrast media was a fall rather than a rise in pulmonary vascular resistance. No significant changes were detected in the renal circulation after infusion of contrast media.

Acute renal failure in rats. Interaction between contrast media and temporary renal arterial occlusion.

It was demonstrated in rats that renal injury which follows transient renal hypoxia is potentiated by the contrast media metrizoate, ioxaglate, iopamidol and iohexol. Intravenous injection of 1 g I/kg of all four media alone to 82 rats caused no significant increase in serum urea 1, 3 and 7 days later. The percentage increase of serum urea is given in median values and interquartile range (in parentheses). Bilateral renal arterial occlusion alone for 40 minutes in 42 rats increased serum urea one day later by 40 per cent (20-130). Intravenous injection of the media followed in one hour by bilateral renal arterial occlusion for 40 minutes in 104 rats caused serum urea to increase one day later by 130 per cent (70-350) after metrizoate, by 220 per cent (50-380) after ioxaglate, by 290 per cent (60-420) after iopamidol and by 160 per cent (50-330) after iohexol. There were no significant differences between the potentiating effects of the various media on ischemic renal failure.

A micropuncture assessment of the effects of contrast media of different osmolality.

The pathophysiology of radiographic contrast media-induced acute renal failure is unclear. Different causes are suggested, including hypertonicity, charged molecules, and toxicity of the media. This study deals with hemodynamic changes after injection of contrast media of high osmolarity iohexol, and metrizoate. Proximal tubular free-flow and stop-flow pressure (Psf), (the latter a marker of glomerular capillary pressure) were measured before, during, and afer injection of contrast media into the renal artery, compared with saline injection, in both normal rats and rats with ureteral obstruction (UO). Urine and electrolyte excretion also were examined. Metrizoate caused an initial decrease in Psf, from 37 to 20 mm Hg, followed by an increase to 81 mm Hg, and the value remained high for 10 minutes. During UO, the elevation of Psf was prolonged. Iohexol injection had a less marked effect. The change in glomerular capillary pressure may be dependent on the osmolarity of the contrast agent.

Cytostatic effects of radiographic contrast media in synchronized cell cultures.

The cytostatic effects of conventional high osmolal ionic contrast media (meglumine-calcium metrizoate and Na-metrizoate) and new low osmolal nonionic contrast media (iohexol and iopamidol) in synchronized cell cultures were tested. The cell-cycle prolongation was most pronounced when the contrast media were added in the G1 phase, but there was also a marked effect when the contrast media were added in the S phase or late in the G2 phase. The cytostatic effect even persisted into the first cell cycle following the termination of the exposure. All four contrast media exerted effects stronger than that of equiosmolal saline. Iohexol and iopamidol produced a more severe effect than meglumine-calcium metrizoate and Nametrizoate at equal osmolality. Thus, the cytostatic effect of contrast media cannot be explained only by hypertonicity; the contrast media must have an additional specific cytostatic effect. When the cytostatic effect was related to iodine concentration, the new low osmolal nonionic contrast media influenced the cell cycle less than the conventional high osmolal ionic contrast media.

Effects of radiographic contrast media on monolayer cell cultures.

The relationship between iodine concentration, osmolality, and toxicity for nine different contrast media was studied. High osmolal conventional ionic contrast media (Na-metrizoate, Na-iothalamate, meglumine/Na-diatrizoate, meglumine-calcium-metrizoate) and the new low osmolal nonionic (Metrizamide, iopamidol, iohexol) and ionic dimer (Meglumine/Na-ioxaglate) contrast media were tested. Monolayer cell cultures of human cervical carcinoma in situ cells were used as a test system. The toxicity of contrast media on cell cultures was strongly dependent on the osmolality, and different contrast media with the same osmolality had about similar effects on the cell cultures. However, contrast media seem to have some additional and more specific effects since equiosmolal saline and mannitol were better tolerated. When the toxicity was related solely to iodine concentration it emerged that the new low osmolal contrast media were much better tolerated than the high osmolal conventional contrast media.

Nephrotoxicity of ionic and non-ionic contrast media in aorto-femoral angiography.

Nineteen patients examined with aorto-femoral angiography were randomized into two contrast medium groups (meglumine metrizoate and iohexol). Urine activity of beta-hexosaminidase, a specific renal enzyme, was determined before and on three occasions after angiography. No change of beta-hexosaminidase activity was found after angiography with iohexol, while there was a significant increase after examination with meglumine metrizoate. This indicates that meglumine metrizoate even following injection into the abdominal aorta damages renal cells which could not be shown with iohexol as contrast medium. We therefore recommend that at least patients with impaired renal function should be examined with the non-ionic contrast medium iohexol to minimize the danger of further damage to the kidneys and a possible renal failure.

Contrast enhanced brain CT comparison between iohexol and metrizoate.

The commonly used contrast medium metrizoate (Isopaque Cerebral) or the new nonionic iohexol was injected intravenously for enhancement of cranial CT in a randomized double blind study. Each group consisted of 105 patients. No serious reactions occurred. Ten patients receiving metrizoate had minor reactions of mainly allergic type, whereas only one patient receiving iohexol reacted. No differences in enhancement efficiency could be observed.

Contrast media-induced nephrotoxicity. Survey and present state.

Reports of renal failure induced by contrast media are increasing. Adverse effects of contrast media on kidney function include diuresis, changes in renal blood flow, osmotic nephroses, albuminuria, enzymuria and, most important, glomerular filtration rate. Animal studies indicate that the new nonionic contrast medium, iohexol, has fewer adverse effects on kidney function than the ionic media currently used. Three clinical studies offer some evidence of the effect of iohexol on renal function, but it is not yet possible to conclude that lower nephrotoxicity found in animals will also be found in man. Further clinical studies are warranted, and careful monitoring of contrast media clearance is recommended in all high-risk patients.

Pulmonary edema following high intravenous doses of ionic contrast media. Effect of the anion composition and concentration.

High intravenous doses of diatrizoate are known to induce a profound degree of pulmonary edema which is dose- and injection rate-dependent in the rat. In this study, meglumine salts of diatrizoate, iothalamate, and metrizoate were evaluated for their capacity to induce pulmonary edema following intravenous injections. Differences in anion composition or concentration of diatrizoate meglumine/sodium salts did not cause significantly different degrees of pulmonary edema.

Acute damage to human endothelial cells by brief exposure to contrast media in vitro.

Cultured endothelial cells derived from human umbilical cord veins were labeled with Na2 (51Cr)O4 and exposed to pure isoiodinated contrast media or control solutions for 10 minutes to simulate the effects of intravenous injections of contrast media on the human endothelium. Metrizamide, iohexol, iopamidol, meglumine/Ca metrizoate (300 mg I/ml), meglumine/Na diatrizoate, meglumine/Na ioxaglate, and meglumine/Ca metrizoate (200 mg I/ml) were tested. Iso-osmolal mannitol solutions were used to determine the portion of injury that was due to the effects of osmolality. Up to six times more chromium-51 was released from the cultures following exposure to the two hyperosmolal ionic contrast media (meglumine/Na diatrizoate and meglumine/Ca metrizoate) than with exposure to the least toxic agent, iopamidol. The dimer ioxaglate and the three nonionic agents (iohexol, metrizamide, and iopamidol) gave a chromium-51 release rate that was almost equal to or lower than that of 0.9% saline. Follow-up of the washed cultures for 24 hours showed no residual toxic effects.

Human endothelial cell culture as an evaluation system for the toxicity of intravascular contrast media.

Endothelial cells in primary cultures from human umbilical cord veins were incubated with various radiographic contrast media in increasing concentrations up to approximately 60 mgI/ml for 24 hours in order to study their toxicity. Cell death was recorded with the chromium-51 (51Cr)-release method and controlled by dye exclusion tests, Coulter counting, and protein determination. The hyperosmolar, ionic contrast medium, meglumine metrizoate, was far more toxic to the endothelium than the nonionic media, metrizamide and iohexol, which are far less hyperosmolar. The 51Cr-release test on endothelial cultures provides a simple and useful technique in the evaluation of various intravascular contrast media and their components.

Double blind comparison between iohexol and metrizoate in phlebography of the lower limb.

A new, non-ionic low osmolar contrast medium, iohexol 240 mg I/ml, has been tested in a randomized double blind parallel investigation versus meglumine-Ca metrizoate 200 mg I/ml. The study was performed to evaluate the suitability of the contrast medium in phlebography. No post-phlebographic complications were seen in the 24 patients examined with iohexol 240 mg I/ml or in 8 patients examined with iohexol 300 mg I/ml. In the 19 patients examined with metrizoate 200 mg I/ml, 7 had a post-phlebographic thrombotic complication (37%). The radiographic image quality was not significantly different between the two contrast media, neither were the immediate side effects during contrast injections. It has thus been shown that iohexol is a suitable contrast medium in phlebography of the lower limb and that it is preferable to conventional contrast media.

Iohexol in coronary angiography. A comparison of ionic and non-ionic contrast media.

Iohexol (350 mg I/ml) has been compared with meglumine-Na-Ca metrizoate (370 mg I/ml) in selective coronary angiography in 37 adult patients. Iohexol was very well tolerated and resulted in only minor changes in blood pressure and ECG parameters. Changes in blood pressure and R-R interval were significantly more marked following injections of metrizoate than after injections of iohexol. Arrhythmias were not observed following injections of iohexol, while two patients had AV block II after injection of metrizoate. Both contrast media gave similar and adequate demonstration of the coronary vessels. The findings suggest that iohexol has distinct advantages over metrizoate in selective coronary angiography.

Tolerability and usefulness of iohexol in cardioangiography. II. A double blind comparison with metrizoate.

The new non-ionic contrast medium iohexol (Omnipaque) was compared with the ionic medium sodium meglumine calcium metrizoate (Isopaque Coronar) in a double blind, two-group trial. Iohexol resulted in significantly fewer and smaller subjective reactions than metrizoate. Changes of left ventricular and aortic pressure were statistically significantly less after injection of iohexol than of metrizoate. ECG recordings did not significantly differ in the two groups. Analysis of biochemical parameters showed no statistical differences between the two groups. Determination of serum enzyme activities revealed no signs of myocardial injury, and no impairment of glomerular filtration rate was detected by radionuclear renal function test. Similar radiographic quality was obtained with both media.

Comparison of iohexol and meglumine-Na-Ca metrizoate in visceral angiography.

Visceral angiography was performed in a double blind study in 54 patients using iohexol (350 mg I/ml) and meglumine-Na-Ca metrizoate (370 mg I/ml). No significant increase in serum values of either hepatic or pancreatic enzymes or electrolytes was registered. Both contrast media gave excellent demonstration of arteries as well as veins. Iohexol gave far less sensation of heat during the injections than metrizoate.