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[The effect of x-ray contrast agents on the concentration and size of immune complexes in the blood].

Bilignost, iodamide and triombrast were shown to increase the concentration and to decrease the size of the rat blood serum immune complexes in vivo and in vitro. A decrease of the size of immune complexes was also observed during angiography with the use of triombrast in humans. According to the relation to the action of roentgen contrast media on the concentration and size of immune complexes humans and rats can be divided in "sensitive" and "tolerant" ones.

Animals↗

Decrease of plasma prekallikrein and kallikrein inhibitors during intravenous phlebography.

Complex contact activation systems may have major involvement in side effects of i.v. contrast media. To investigate this, quantitative measurements of several factors (plasma prekallikrein, kallikrein inhibitory activity, haematocrit, alpha-2-macroglobulin, antithrombin III, alpha-1-antitrypsin and beta-thromboglobulin) were made before and after i.v. contrast phlebography in two groups of patients (each containing 21 patients) with no thrombosis, using a high- (meglumine iodamide) and a low-osmolality (ioxaglate) contrast medium. A statistically significant decrease in plasma prekallikrein was observed after the high-osmolality contrast medium, which is a sign of the activation of the kallikrein-kinin system and an indicator of the activation of the intrinsic coagulation. These events may play an important role in the adverse effects of contrast media.

Antithrombin III↗

Experience with low osmolar contrast media a clinical and experimental study.

Low-osmolar contrast media were used in 546 patients: 371 with ioxaglate, 80 with iopamidol, 95 with iohexol. The image quality was good in all cases. Heat was observed in one patient (iopamidol) and pain was observed in 7 patients (ioxaglate: 4, iopamidol: 1, iohexol: 2). Blood pressure, heart rate as well as the parameters, BUN, SGOT and serum bilirubin showed no significant changes. Our experimental investigations were performed on 101 dog kidneys. Selective renal angiography was performed with 10 ml of contrast media metrizamide, ioxaglate, iopamidol, or iohexol. Comparative preparations were the high-osmolar contrast media iodamide and metrizoate. Untreated kidneys and kidneys given saline constituted baseline controls. Histological examination of tissues 3 and 24 hours after the injections showed moderate reversible changes (metrizamide 15/21, ioxaglate 5/17, iopamidol 2/18, iohexol 2/26). Electronmicroscopy (6 iohexol) showed no significant changes.

Animals↗

[Effect of contrast media on the structure and function of hepatocyte plasma membranes].

The cholecystographic radiopaque agents, adipiodon and endographin, unlike the urographic contrast agents, triombrin and iodamide, decrease the fluorescence intensity of hydrophobic probes 1-anilinonaphthalene-8-sulfonate and 4-dimethylaminochalcone in plasmic membranes (PM) of rat hepatocytes primarily at the expense of the lowering of the constant of probe association with the membranes. The similar but less marked effects were discovered in experiments with lecithin lyposomal preparations. As regards the intensity of action, cardiotrast and triotrast an intermediate position between the two groups of radiographic contrast agents. Adipiodon and endographin induce an inhibition of membranous Mg+2 (Na+, K+) ATPase, which correlates with their effect on the structure of the hepatocyte PM. The data obtained allow a conclusion that, unlike the urographic agents, the cholecystographic radiopaque agents are bound to the definite areas of the hepatocytic PM and provoke alterations in the activity of membranous APTase because of the conformational rearrangements of the membranes.

Acetrizoic Acid↗

[Abnormal renal angiograms caused by injection of contrast medium].

The anomalies caused by the injection of contrast medium were studied in animal experiments with dogs on 53 kidneys, and on clinical material, via the renal angiograms of 130 patients. In these trials vascular spasms were seen or, alternatively, filling defects in the parenchyma. Both were using the classical tri-iodated contrast medium iodamide and the monoacid dimeric contrast medium with low osmotic pressure (Hexabrix); in several cases, histological changes (for example, necroses of the tubular epithelium) were seen. Anomalous angiograms were also seen in the human experiments, especially in case of incorporation of large quantities of contrast medium and selective use of a thick catheter. Anomalies were more likely to occur in kidneys with diseased parenchyma.

Angiography↗

[Effect of tri-iodine-containing x-ray contrast substances on the blood coagulation system in an experiment].

Experiments on white rats were made to examine the time course of hemocoagulation changes induced by intravenous injection of the triiodine-containing radiographic contrast agents, bilignost, verografin, triombrast, iodamide-380. The substances were found to exert a biphasic action: an initial decrease in the total coagulation is replaced by a tendency toward hypercoagulemia. In experiments in vitro, the radiographic contrast agents increased the time of plasma recalcification, the prothrombin time and retarded the thrombin-fibrinogen and thrombin-plasma reactions. Bilignost produced the most marked hypocoagulemia. It is suggested that the direct effects of the drugs on blood coagulation involve a decrease in the total blood coagulation activity.

Animals↗

Late haemodynamic response to metrizamide and ioxaglate in canine renal angiography. Preliminary report.

The renal blood flow as examined in six dogs for 2 h after contrast agent injection into the renal artery using the dye dilution method. After injection of an ionic contrast agent (iodamide) there was an initial vasodilatation and later constriction, but the blood flow was back to normal after 10-15 min. Ioxaglate caused a similar initial response, but after a relatively large dose the blood flow remained below normal for 2 h. Metrizamide caused an immediate reduction in the blood flow, which remained constantly reduced for 2 h. A total cessation of the renal blood flow was seen in two cases.

Angiography↗

Contrast media-induced side effects on excitation and conduction of electrical activity in the heart on intracardiac application. Investigations in anaesthetized dogs.

In several series of experiments with intracardiac application in anaesthetized dogs, the following contrast media were tested for their adverse effects on excitation and conduction of electrical activity in the heart. Diatrizoate, lysine-diatrizoate, lysine-sodium-diatrizoate, ioxaglate, iopamidol, iodamide, ioxitalamate, ioglicinate and metrizamide. Blood pressure and, using the His' bundle-ECG technique, the parameters P0-P1 (heart rate), A1-H1 period (conduction time in the AV-node), and H1-V1 period (conduction time in the TAWARA branches) were measured. A statistical correlation exists between osmolarity and blood pressure (higher osmolarity causes a greater decrease in blood pressure), as well as between osmolality and decrease in heart rate (higher osmolarity causes a greater decrease in heart rate). The delay in conduction time in the AV-node correlates only with viscosity and sodium content (increased viscosity with increased sodium content delays the time of conduction). A tendency towards delay in conduction in the TAWARA branches could not be correlated to any one of the physico-chemical parameters studied.

Anesthesia, General↗

[The effect of x-ray contrast media on the amount of thromboxane and prostacyclin in the blood of man and rats in vivo and in vitro].

The in vivo and in vitro effects of radioopaque agents such as bilignost, iodamide, and triombrast on blood thromboxane B2 (TxB2) and prostacyclin levels were studied in man and rats. These radioopaque agents were demonstrated to increase prostacyclin levels and to decrease TxB2 in the plasma by 40%, as evidenced by urography when given in vivo (1-2 g/kg) and in vitro (2.5.10(-2) M and 2.5.10(-3) M).

6-Ketoprostaglandin F1 alpha↗

Measurement of N tau-methylhistamine concentrations in plasma and urine as a parameter for histamine release during anaphylactoid reactions.

N tau-methylhistamine concentrations in plasma and urine were determined using a newly developed simultaneous determination for histamine and N tau-methylhistamine, based on isotope dilution mass fragmentography. Three groups of patients were investigated: patients receiving intravenously-administered iodamide for excretory urography, patients receiving a wasp-sting challenge, and patients treated with an intravenously-administered muscle relaxant. In all patients showing a distinct systemic anaphylactic or anaphylactoid reaction histamine and N tau-methylhistamine concentrations were found to be elevated. From the results of this study it can be concluded that N tau-methylhistamine in plasma and urine is a good parameter for histamine release, and that the determination of this histamine metabolite are less hampered by possible artefacts (due to basophil disrupture, a very short half-life time or bacterial production) than determinations of histamine itself.

Anaphylaxis↗

Contrast media: the relation of chemical structure, animal toxicity and adverse clinical effects.

Chemotoxicity and osmotoxicity of contrast media (CM) are determined by chemical structure. The lower the chemotoxicity and osmotoxicity of the CM, the less animal toxicity and higher clinical tolerance in humans will be achieved. Nonionic monomers such as iohexol and iopamidol in iodine-equivalent concentrations have approximately half the osmolality and therefore half the osmotoxicity of ionic monomers such as diatrizoate, iodamide, iothalamate and metrizoate. Absence of carboxyl groups in nonionic CM, as opposed to the presence of carboxyl groups in ionic CM, results in a lower chemotoxicity in nonionic CM. Similarly, a larger number of hydroxyl groups in nonionic CM than in ionic CM result in a lower chemotoxicity. The lower chemotoxicity of nonionic CM is reflected as a higher subarachnoid and intravenous tolerance both in animals and in the clinical setting.

Animals↗

Endothelial permeability increase produced by angiographic contrast media.

Permeability changes of the thoracic aortic wall of the rat were examined under light microscopy using the silver staining method. Methylglucamine salts of common angiographic contrast media and metrizamide were tested using a constant iodine concentration. Statistically significant differences between these media were found. The contrast agents were divided into three groups according to the extent of increasing endothelial damage: 1. Metrizamide and methylglucamine diatrizoate, 2. Methylglucamine metrizoate in the presence of calcium and methylglucamine iodamide, 3. Methylglucamine iothalamate. The osmolality of the contrast media was determined. The ionic contrast agents were equal in hypertonicity and metrizamide was nearly isotonic. The endothelial damage caused by the radiographic contrast media seems to depend both on chemical structure and on hypertonicity.

Animals↗

Miscellaneous adverse effects of low-versus high-osmolality contrast media: a study revised.

The authors analyzed data from two recent articles in Radiology in which the quality and results of randomized control trials (RCTs) comparing the efficacy or safety of the low-osmolality contrast media (LOM) iopamidol, iohexol, and ioxaglate with that of the high-osmolarity contrast media (HOM) diatrizoate, iodamide, iopamide, iothalamate, and metrizoate were assessed. One conclusion in the source articles was that no differences were seen between the two groups of contrast media in frequency of nausea, vomiting, and urticaria. However, the LOM group included both nonionic LOM (NIM) and the ionic contrast medium ioxaglate. The authors found that various complications associated with the use of contrast media were much less common with NIM than with HOM; statistically this lower frequency is highly significant. This difference was obscured in the previous studies by the pooling of RCTs in which the less toxic NIM were used and RCTs in which the more toxic ionic contrast medium ioxaglate was used.

Contrast Media↗

Delayed reactions to urographic contrast media.

Reactions to urographic contrast media occurring after the patient had left the department were studied by giving patients a questionnaire to complete. 841 questionnaires were returned (about 80% of those issued). 70% of patients had no delayed reactions and 7% expressed a positive response to urography i.e., found the procedure interesting and not unpleasant; 13% had arm pain, 5% a rash and 14% had a variety of reactions, many of which were the same as those described in iodism. Women had significantly more rashes (7%) than men (4%) and those media containing the meglumine or iodamide ions caused more rashes than other media. Conray 420 caused more arm pain than Conray 280 or the non-ionic media, which would be expected from the known effects on vascular endothelium. Symptoms of iodism were equally common from the various contrast media.

Adolescent↗

Inhibitory effect of various radiographic contrast agents on secretion of thyroxine by the dog thyroid and on peripheral and thyroidal deiodination of thyroxine to tri-iodothyronine.

In previous studies we have found that the cholecystographic contrast agent ipodate induced a rapid, sustained and reversible inhibition of thyroxine (T4) secretion from perfused dog thyroid lobes. This type of inhibition of thyroid secretion has not been observed previously. To evaluate whether this effect is unique for ipodate, ten other iodine-containing radiographic contrast agents were tested. The four agents used for cholecystography (iocetamate, iodipamide, ioglycamate and iotroxate) all induced rapid inhibition of T4 secretion from TSH-stimulated perfused dog thyroid lobes, while none of six agents predominantly excreted through the kidneys (amidotrizoate, metrizamid, metrizoate, iodamide, diodone and ioxithalamate) influenced T4 secretion significantly. All the cholecystographic agents inhibited T4 deiodinases from dog thyroid and liver. Diodone also inhibited the deiodinases while none of the other compounds tested had any effect. The results indicate that the structure necessary to inhibit thyroid secretion is common to a number of cholecystographic agents and that it could be related to the structure responsible for the inhibitory effect of cholecystographic agents on T4 deiodinases.

Animals↗

Prevention of postvenographic thrombosis by heparin flush: fibrinogen uptake measurements.

The incidence of postphlebographic venous thrombosis was investigated by 125I-labeled fibrinogen uptake tests in 60 patients whose veins were flushed with saline solution containing 10,000 IU of heparin after leg phlebography. Ionic methylglucamine iodamide was used as the contrast medium. In six patients superficial thrombophlebitis extending from the contrast-medium injection site was observed after phlebography. The incidence of deep venous thrombosis was 3.3%, significantly less than that reported for studies using triiodinated ionic contrast media without flushing the veins with a heparin solution. It is comparable to the incidence of venous thrombosis reported after using nonionic contrast media. The authors conclude that flushing the veins with heparinized saline solution can improve the safety of phlebography considerably.

Adult↗

Level of plasma prekallikrein and its inhibitors in reactors and nonreactors during intravenous enhancement with contrast media.

Complex contact activation systems may play a major role in the side effects of i.v. contrast media (CM). This is why quantitative measurements of several factors (plasma prekallikrein, hematocrit (hct), alpha-2-macroglobulin, alpha-1-antitrypsin, and C1-esterase inhibitor) were determined prior to and following the injection of CM during body CT examination in 5 patient groups, each (n = 10) receiving one of 5 different CM, including ioxaglate, meglumine iodamide, metrizamide, iohexol, and meglumine diatrizoate. The initial plasma prekallikrein level was available from 45 patients and was statistically lower in reactors (mean 90.6 mumol TAMe/ml/h; n = 13) than in nonreactors (mean 107 mumol TAMe/ml/h; n = 32) (p = 0.006), but there was no statistically significant difference in the decrease of plasma prekallikrein before and at 5 min after the injection for those 2 groups. The initial plasma C1-esterase inhibitor level was lower in reactors, while the plasma alpha-2-macroglobulin level was higher in that group than in nonreactors. The results indicate that the measurement of plasma prekallikrein combined with plasma C1-esterase inhibitor and alpha-2-macroglobulin measurement could be useful when predicting which patients are prone to CM reactions.

Blood Proteins↗

X-ray contrast media induce aortic endothelial damage, which can be prevented with prior heparin treatment.

X-ray contrast media induce damage to the endothelial layer of vessels and initiate the formation of thrombosis, which is a complication for clinical diagnostic procedures. The future determination of the mechanisms, which underlie the damaging effect of X-ray contrast medium on vascular wall cells, especially vascular endothelium and possible prevention of this damage by vasoprotector, will result in a larger application in diagnostic procedures. The aim of the present study is to analyze the effect of X-ray contrast media (Verographin, Iodamid and Iodolipol) on the arterial endothelium morphology by using ultrastructural techniques (scanning and transmission electron microscopy, SEM and TEM respectively). Experiments have been carried out on New Zealand white rabbits (6 month old) and Wistar rats (6-8 month old) after a single injection of X-ray contrast media with and without prior heparin treatment. Control groups of animals were exposed to the same procedure but without X-ray contrast media injection and only received isotonic saline solution. The following time points were selected: 1, 6, 24, 72 h and 7 days. At the end of the experiments, animals were anesthetized by pentobarbital and then perfused with a balanced buffer for 1 min and followed by perfusion fixation with Karnovsky's fixative containing buffered solution of 2.5% paraformaldehyde and 2.5% glutaraldehyde (pH 7.36) at least 30 min. The aortic tissue was removed and immediately placed into a fresh portion of the same fixative. Aortic samples were then prepared for scanning and transmission electron microscopy (SEM and TEM respectively). Immediately after the injection of X-ray contrast media, the number of microvilli and blebs on the luminal surface of the endothelial cells (EC) significantly increased. Very often, nuclear portions of the EC sharply protruded into the vessel lumen. Clusters of spindle-shaped EC were seen throughout the endothelial monolayer. These changes persist through the 72-h period after X-ray contrast media injection. Moreover, the desquamation and denudation of the EC from the monolayer is often observed and this is accompanied by the presence of a microthrombus on the vessel surface. Seven days after the post-injection period, endothelial monolayers still show severe damage, which often coexists with the presence of a different sized microthrombus on the vessel surface. However, the degree of lesion formation in most areas is substantially decreased as compared to the early period of post-injection (24 and 72 h). Heparin treated group shows intact morphology similar to the control experimental groups (saline injected group). Infrequently, minimal morphological changes of the endothelium, such as increased number of microblebs and microvilli, were seen with heparin treatment. We conclude that the negative side effects of the X-ray contrast media can be eliminated by a single injection of heparin or other vasoprotector prior to the diagnostic procedure.

Animals↗