Granulocyte chemotaxis before and after urography. Influence of four different radiographic contrast media.

Granulocytes isolated from whole blood of 10 volunteers with Hypaque/Ficoll or Percoll gradient centrifugation showed a significant inhibition of their chemotactic response when incubated with diatrizoate. The influence of 4 different i.v. injected radiographic contrast media (CM) on granulocyte chemotaxis was evaluated using the under agarose assay. Each CM was injected in 10 consecutive outpatients referred for urography. Cells and serum were obtained before and 20 min after the injection of CM. Autologous serum was used as chemoattractive agent, and the cell suspensions from both samples were tested against serum drawn both before and after the injection of CM. No significant changes in granulocyte chemotaxis or the chemotactic potential of serum were seen. Furthermore, there was no change in the chemotactic response towards homologous serum or N-fmlp after injection of diatrizoate or iohexol. In conclusion, the investigation did not unveil any change in granulocyte chemotaxis 20 min after the injection of CM in the 40 subjects studied.     

Granulocyte chemotaxis. Chemoattractive properties of a synthetic tripeptide are inhibited by radiographic contrast media

The under agarose method for evaluation of leucocyte chemotaxis was used to investigate the effect of radiographic contrast media (CM) on granulocyte locomotion. The CM tested had no chemoattractive properties. CM inhibited N-fmlp, a synthetic formylated Met-tripeptide, which is a strong chemotactic agent and an analogue to chemotatic peptides produced by bacteria. The inhibition of N-fmlp was most pronounced for diatrizoate. Equiosmolal saline was not so inhibitive. Therefore, some part of the inhibition was caused by factor(s) other than hyperosmolality inherent in the CM solution.     

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.     

Influence of radiographic contrast media on phagocytosis

To evaluate the influence of radiographic contrast media (CM) on human polymorphonuclear leucocytes (PML), the ability of these cells to ingest latex particles after in vitro exposure to five different radiographic contrast media was investigated. All CM inhibited the phagocytic properties of PML. The inhibition was dose dependent. The inhibitory effect was partly due to hyperosmolality but CM specific inhibition was also evident.     

Ventilatory effects of radiographic contrast media.

Respiratory adverse reactions have been reported with the use of contrast media. This study investigates the effects of different radiographic contrast media (RCM) on ventilation and blood gases. Tidal volume and respiratory rate of male Wistar rats anaesthetised with Inactin (100 mg kg-1 intraperitoneally), were measured continuously by integration of tracheal airflow. Contrast media (diatrizoate 370, ioxaglate 320 and iopromide 300) or mannitol controls matched for volume, pH and osmolarity (4 ml kg-1) were administered via a jugular cannula (n > or = 6 per group). Carotid artery blood was sampled at 2, 7, 12, 17, 25 and 30 min post-injection for PaO2, PaCO2 and pH. Systemic blood pressure was monitored from the same cannula. No significant reduction was observed in minute ventilation (tidal volume x respiratory rate per minute) with any of the contrast media. All contrast media and control solutions produced a fall in PaO2 within 4 min; returning to basal levels at 10 min (diatrizoate 35.6% (p < 0.05), ioxaglate 15.2% (p < 0.02), iopromide 16.2% (p < 0.01); controls: 17.3% (p < 0.01), 13.5% (p < 0.02) and 12.0% (NS), respectively). The fall in PaO2 induced by diatrizoate was significantly (p < 0.05) larger in comparison to the other groups. Ioxaglate, iopromide and their mannitol controls induced a comparable fall in PaO2. There was a concurrent rise in PaCO2 and fall in pH that reached significance for diatrizoate (p < 0.01). The changes in blood gases with RCM administration cannot be explained by changes in ventilation and may be due to an effect on pulmonary perfusion.     

Iodinated radiographic contrast media possess antioxidant properties in vitro

PURPOSE: To study potential properties of iodinated radiographic contrast media (IRCM) for intravascular use in in vitro free radical generating reactions. MATERIAL AND METHODS: Superoxide (*O2-) and hydroxyl (*OH) radicals were generated in xanthine oxidase and Fenton reactions. *O2- was assayed by the nitroblue tetrazolium (NBT) method, whereas *OH was assayed by an aromatic hydroxylation (2-hydroxybenzoic acid) method. Total antioxidant status (TAS) of test substances was determined by a colorimetric assay. Finally, acetyl-cholinesterase (AChE) activity was measured in the absence and presence of IRCM. RESULTS: High concentrations (>50 mM) of IRCM inhibited *O2- production, ionic more than non-ionic IRCM. Medium concentrations (25-50 mM) of IRCM reduced *OH production, and both types of IRCM were equally potent. Low concentrations (<25 mM) of non-ionic IRCM displayed higher antioxidant capacity than their ionic counterparts when tested in the TAS assay. Visipaque 320 (iodixanol) was found to have the highest TAS value, followed by Omnipaque 350 (iohexol), Hexabrix 320 (ioxaglate), and Urografin 370 (diatrizoate). CONCLUSION: IRCM have in vitro antioxidant properties in concentrations relevant for their clinical application. These properties may therefore be of potential importance when evaluating IRCM effects in vivo, particularly those concerning cardiovascular and renal function.     

Interaction of ligandin with radiographic contrast media.

Ligandin (Y protein) is an abundant cytoplasmic glutathione transferase present in liver, kidney and gut in various animals and man. Its interaction with four radiologic contrast media (Telepaque, 3-(3 amino-2,4,6, triiodophenyl -2 ethylpropanoic acid, sodium salt; Hypaque, sodium -3, 5-diacetamido-2,4,6,-triiodobenzoate; Cholografin, N,N'adipyl-bis-(3-amino-2,4,6-triiodobenzoic acid) N-methyl-glucosamine; Diodrast, 3,5-Diiodo-4-pyridone-N-acetic acid, Diethanolamine Salt was investigated by observing inhibitory effects on the enzyme-catalyzed conjugation of glutathione with 1-chloro-2, 4-dinitrobenzene. Lineweaver-Burk plots of reciprocal initial velocity versus reciprocal inhibitor concentrations at fixed glutathione and chlorodinitrobenzene concentrations demonstrate non-competitive inhibition by all contrast media except Diodrast. No conjugates of contrast media with glutathione were formed. It is postulated that intracellular accumulation of contrast media is aided by intracellular binding with ligandin. Inhibition of the GSH transferase activity of ligandin can disrupt the mercapturate formation, an important detoxification process.     

Influence of radiographic contrast media on granulocyte enzymes and complement during uncomplicated urographies

Four different radiographic contrast media (RCM) were used for i.v. urography in 40 patients, none of whom had complications. No rise in C3d was observed for any of the RCM, indicating that complement was not activated. However, significantly decreased values for CH50 were detected when the non-ionic RCM iopamidol and iohexol were used, and this may be due to interaction between the RCM and the complement molecules. Significantly increased numbers of neutrophils were observed in patients receiving ioxaglate, iohexol and diatrizoate, which may be due to inhibition of granulocyte adherence. No rise in the concentration of elastase and lactoferrin was observed. On the other hand, significantly decreased values of elastase were seen after injection of diatrizoate, which may be due to inhibition of the degranulation process by this 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.     

Eosinophilia caused by iodinated radiographic contrast media

Statistically significant eosinophilia was noted in the peripheral blood of a group of 108 patients 48 h after the administration of iodinated radiographic contrast medium (RCM). The duration of eosinophilia was approximately 6 days. Eosinophilia had no accompanying clinical symptoms except for two cases where urticaria appeared. The incidence of eosinophilia was irrespective of dosage or type of RCM. Possible mechanisms responsible for eosinophilia have been considered. Since eosinophilias of other aetiologies are common, it is of practical importance to distinguish these from RCM-induced eosinophilias.     

Review article: Effects of radiographic contrast media on the lung

The pulmonary adverse effects of intravascular use of water soluble radiographic contrast media (RCM) include bronchospasm, pulmonary oedema and increase in the pulmonary arterial blood pressure (Ppa). Symptomatic bronchospasm is rare but subclinical increase in airways resistance is common after intravascular injection of RCM. Experimental studies have demonstrated that the low osmolar ionic dimer ioxaglate can induce significant bronchospasm in comparison with other types of RCM. Histamine and endothelin, which are potent bronchoconstrictors and released in response to the administration of RCM, do not seem to mediate the bronchospastic effect of RCM. Pretreatment with corticosteroids or antihistamine does not appear to prevent RCM induced bronchospasm, but the administration of beta(2) adrenergic agonist can abolish this adverse effect. RCM induced pulmonary oedema can be secondary to endothelial injury causing an increase in the permeability of the microcirculation. It may also occur in patients with incipient cardiac failure, when large doses of RCM particularly of the high osmolar type are used. A rise in Ppa induced by RCM seems to be secondary to an increase in pulmonary vascular resistance through direct effects on the pulmonary circulation. Low osmolar non ionic monomers induce the least changes in the pulmonary circulation and should be the contrast media of choice for intravascular use in patients with pulmonary hypertension. The mechanisms responsible for the effects of RCM on airway resistance and pulmonary circulation remain unclear. Intrabronchial administration of high osmolar water soluble RCM is dangerous and can induce severe bronchial irritation and pulmonary oedema. Low osmolar RCM are well tolerated by the lungs following aspiration with minimal histological reaction.     

Formation of potential antigens from radiographic contrast media

The use of radiographic contrast media is occasionally accompanied by more or less serious adverse effects, evidently of complex etiology, following intravascular administration. Some of these reactions are suspected of having an allergic basis. The in vitro and in vivo formation of iodinated serum proteins following gamma irradiation in the presence of two commonly used radiographic contrast media is demonstrated. Non-toxic concentrations of ascorbate present during the irradiation is shown to prevent the formation of such iodo-proteins in vitro as well as in vivo. The amounts of potentially antigenic iodoprotein formed during radiographic procedures will certainly be very small, but this quantity may be sufficient to elicit a hypersensitivity reaction in cases when an individual has been previously sensitized to immunologically similar iodo-proteins, a mechanism that could account for certain rare and unpredictable reactions. The radiation induced formation of iodo-proteins may also serve as a model for the formation of iodine containing antigens mediated by a free radical mechanism, i.e. in the metabolism of iodinated compounds like erythrosine, a widely used colouring agent for certain foods.     

Effects on the ATP content of cultured cells after radiographic contrast media exposure. Evidence for accumulation of contrast media in cultured cells

The ATP content of cultured cells after exposure to meglumine-calcium metrizoate, sodium metrizoate, iohexol, iopamidol and saline was studied. Initially, the ATP content diminished rapidly for a short period and thereafter slowly during the incubation. After incubation with contrast media or saline, the ATP content slowly increased to normal when the cells were reincubated with fresh nutrient medium. Different contrast media and saline with the same final osmolality produced a similar effect on the ATP content of the cultured cells. Cellular association of meglumine-sodium diatrizoate, sodium metrizoate, sodium-iothalamate, iohexol and iopamidol was also examined. The established cell line NHIK 3025 as well as primary cultures of human umbilical endothelium were found to accumulate contrast media in a time- and concentration-dependent manner. When the incubation was carried out at 4 degrees C, the cellular accumulation of contrast medium was less than 35 per cent of that seen at 37 degrees C. It therefore seems that energy-dependent processes are involved to some degree.     

Influence of the cation on the side-effects of urographic contrast media.

The incidence of side-effects produced by meglumine diatrizoate and meglumine-, meglumine-calcium-, and sodium-calcium-magnesium metrizoate, was compared in 800 urographies. Patients older than 60 years seem to have less side-effects than younger patients. The incidence of sensation of warmth seems to be higher in patients who have had previous urographies, compared to those who are examined for the first time. The incidence of this effect is higher for the sodium-calcium-magnesium salt of metrizoate, than for other salts of metrizoate.     

Plasma histamine levels following administration of radiographic contrast media

The effect of two conventional high-osmolality and two new low-osmolality contrast media on plasma histamine levels has been examined. The study population included 25 patients undergoing intravenous urography with Urovison 58% (sodium and meglumine diatrizoate), 24 patients receiving intravenous Hexabrix 320 (sodium and meglumine ioxaglate) for urography, 16 patients receiving intravenous Iopamiro 370 (iopamidol) for urography and 12 patients receiving Urografin 76% (sodium and meglumine diatrizoate) for coronary angiography. Seventy-four percent of the 77 patients studied suffered adverse reactions ranging from a feeling of warmth and nausea to laryngeal oedema and bronchospasm. Hexabrix 320 and Iopamiro 370 were associated with the least patient discomfort. All contrast agents usually produced a rise in plasma histamine following injection (Iopamiro 370 causing the least change) and the histamine levels then fell towards preinjection values over a space of about 10 minutes. No relationship was observed between the magnitude of the increase in histamine and the severity of the reaction that occurred. However, a relationship was suggested between the mean peak plasma histamine level achieved and the occurrence of a Grade II reaction (i.e., dry retching/vomiting, mild urticaria or rash). These findings raise the probability that histamine contributes to the more severe grades of reaction to radiographic contrast media.     

Influence of radiographic contrast agents on quantitative coronary angiography

Purpose Quantitative angiographic studies on the vasomotility of epicardial coronary arteries are gaining increasing relevance. We investigated whether radiographic contrast agents might influence coronary vasomotor tone and thereby the results of such studies. Methods Coronary angiograms were taken in 12 patients with coronary artery disease at intervals of 5, 3, 2, and 1 min with the low-osmolar, nonionic contrast agent iopamidol 300, and were repeated at identical intervals with the high-osmolar, ionic agent diatrizoate 76%. Results Quantitative cine film analysis demonstrated no significant diameter changes in angiographically normal and stenotic coronary arteries with iopamidol. With diatrizoate, however, normal segments were dilated 2%±2% (p<0.01) after 2 min and 10%±3% after the 1 min interval (p<0.001). Stenoses showed no uniform responses to diatrizoate. Conclusion Low-osmolar, nonionic contrast agents should be preferred for quantitative angiographic studies on epicardial coronary vasomotility. When using ionic contrast agents, injection intervals of at least 3 min are required.