Intracellular penetration and accumulation of radiographic contrast media in the rat kidney.

Radiographic iodine-containing contrast media (meglumine calcium metrizoate, iohexol and meglumine sodium ioxaglate) were injected intravenously in rats. At various intervals after exposure, in situ cryofixation of kidneys was performed. Thin, freeze-dried cryosections were examined by electron microscopy and X-ray microanalysis. In endothelial cells, erythrocytes and tubular cells high dry weight concentrations of iodine were found. Twenty-four hours after iohexol was injected, no trace of iodine was found in the plasma, microvilli or the nuclei of the tubular cells. Small organelle-like compartments in the cytoplasm of the proximal tubular cells contained high concentrations of iodine, whereas no iodine was found in the surrounding cytoplasm. Since no metabolism of contrast medium has been demonstrated, the iodine signals must be emitted from contrast medium molecules. Other elements were also measured, with the concentrations being always within the ranges found in tubular cells of control animals. The detection of intracellular contrast thus does not seem to be an artifact due to cell injury, but rather represents a physiological event in healthy cells in the rat kidney. Our results are in contradiction to the prevailing opinion that contrast media do not enter healthy cells. However, previous conclusions have been based on the use of conventional preparation methods, and the highly water soluble contrast molecules may have been lost during the different steps of fixation and processing.

Incorporation of contrast media in cultured cells.

Monolayer cultures of human prostatic (PC-3) and cervical (NHIK 3025) carcinoma cells were grown on formvar film and exposed to moderate concentrations of contrast agents for 30 minutes to 4 hours. After the exposure period, the monolayers were quickly frozen, and cryosections were examined by electron microscopy and X-ray microanalysis. Iodine was not detected in control cells, but was found in the cells that had been exposed to iodine-containing contrast media. The amount of intracellular iodine increased with increasing exposure dose and time. Because the cells mostly presented no sign of membrane damage, our findings support the view that contrast media have the ability to enter intact cells.

Noninvasive estimation of kidney function by x-ray fluorescence analysis. Elimination rate and clearance of contrast media injected for urography in man.

A noninvasive method for the estimation of kidney function is described. The use of radioactive tracers and the sampling of plasma and urine are omitted. The method has been used in patients referred for urography and who had therefore been injected with routine amounts of iodine-containing urographic contrast medium. After urography, the elimination rates of urographic contrast medium from both serum and finger tissue were determined and compared during a 2-hour period that began two hours after injection of contrast medium. The elimination of iodine in finger tissue was measured noninvasively using x-ray fluorescence analysis. A strong degree of correlation was found between the elimination rates from serum and finger tissue and between the total clearances calculated from the serum and finger measurements. Thus, after urography estimation of kidney function may be obtained as a fringe benefit by x-ray fluorescence measurements of the elimination rate of an iodine-containing contrast medium from tissue or from serum.

Work in progress: reduction of calcium activity by radiopaque contrast media.

An in vitro examination of the effects of radiopaque contrast media anions, cations, additives, and ionic strength on ionic calcium level using ion-specific electrodes was made. The calcium-binding additives sodium citrate and sodium EDTA produced the largest reduction in ionic calcium. At the same iodine concentration the anions diatrizoate, iothalamate, metrizoate, and ioxaglate reduced ionic calcium by essentially the same amount. Sodium compounds reduced ionic calcium more than did meglumine compounds, a difference that is probably related to dissociation. The nonionic compounds iohexol and iopamidol did not reduce ionic calcium significantly. Ionic strength appears to have little direct effect on ionic calcium at and above physiologic levels. All ionic contrast media bind significant amounts of ionic calcium at the high concentrations achieved during selective arteriography. Since the anions are only weak calcium binders supplemental calcium can restore the level of ionic calcium.

Digital subtraction angiography of the carotid arteries. A comparison of iohexol and metrizoate.

An open cross-over investigation of intravenous digital subtraction angiography of carotid arteries was carried out to compare image quality, side effects and pulmonary circulation time of iohexol and meglumine-Na-Ca metrizoate. Successive injections of the two contrast media were given under identical conditions. A significantly higher frequency of artifacts from swallowing and motion was noted after metrizoate injections. A lower frequency of subjective and objective side effects was found following iohexol injections.

Metabolism of urographic contrast media.

The metabolism of ionic and nonionic contrast agents was examined in the rabbit and in humans by specific measurement of iodide present in urine at different time intervals after injection of high contrast medium doses. Interest was focused on the experimental model compound C-29, which was investigated using a 125I-labeled compound, permitting a study of iodide release and the appearance of other metabolites in serum, bile, and urine from rabbits. Large, quantitative, individual variations were found, but in most cases th urine collected from both rabbits and humans contained more iodide than had been injected. A mean of 0.07% of total injected iodine was found within three days after injection of the ionic contrast medium metrizoate. The results with rabbits indicated that this figure may increase to 1% using the nonionic media tested. Direct evidence of metabolism of C-29 was found in bile, where up to 35% of the total radioactivity present in the bile 4-6 hours after injection was identified as a metabolite.

Osmotic effect and solubility of amipaque (metrizamide) in the gastrointestinal tract.

Loops of small intestine in seven rabbits were resected with intact pedicle and ligated at both ends after instillation of 0.5 ml of Gastrografin, Urografin 76%, Amipaque 370 mg I/ml, Amipaque 170 mg I/ml or physiologic saline. After half an hour, the amount of fluid in the loops containing Gastrografin and Urografin 76% increases about twice as much as in the loops containing Amipague with the same iodine concentration because of their greater osmolality. The differences between the loops with isotonic Amipaque (170 mg I/ml) and physiologic saline are not significant. Precipitation occurs when sodium and meglumine salts of diatrizoate, metrizoate, iothalamate, iocarmate and ioglycamate are mixed with 0.05 N HCl. No precipitation occurs with Amipaque, not even when the HCl concentration is as high as 1.2 N. Precipitation occurs when Gastrografin is added to gastric juices with low pH, but is not seen with Amipaque should be a suitable contrast medium for gastrointestinal examinations because of its low osmolality and toxicity and good solubility in gastric juice.

Cerebral distribution of contrast medium and paradoxical location of lesions of the blood-brain barrier in the rabbit.

Lesions to the blood-brain barrier have been investigated in rabbits following constant or intermittent injections of sodium metrizoate into the internal carotid artery at different injection rates. Under certain experimental conditions the lesion to the blood-brain barrier was predominantly located to the brain area supplied by the contralateral carotid artery or the vertebral arteries. It is shown by serial angiography that the application time was shorter within the vascular territory of the paradoxical lesion. The results may imply that a mixture of blood and contrast medium is more vulnerable to the blood-brain barrier than contrast medium alone.