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Intravenous ionic contrast media cause local prostacyclin release in man.

The effect of intravenous administration of ionic contrast media on local release of prostacyclin (PGI2) was investigated in man. Iodamide and ioxaglate, high- and low-osmolality contrast media, respectively, both significantly increased PGI2 levels at the site of injection. Iodamide was the most active, whereas an identical volume of isotonic saline had no effect. This study suggests that local formation of PGI2 may adequately reflect the degree of endothelial irritation that is caused by contrast media and that depends in part on their osmolality.

Contrast Media↗

Assays for plasma complement activation by x-ray contrast media.

Hemolytic complement activity and a C3a radioimmunoassay (RIA) were investigated for their ability to characterize contrast media (CM) with respect to complement activation. The CM tested were commercial formulations of diatrizoate, iodamide, iothalamate, ioxaglate, iohexol, and iopamidol. When plasma was exposed to CM, the hemolytic complement activity decreased and the C3a concentration increased. The C3a assay had a larger dynamic range and therefore more ability to discriminate among the CM. Using C3a data from pooled plasma or from individual donors' plasma, nonionic iopamidol (as Isovue 300) had lower complement-activating potential (P less than .005 and P greater than .05, respectively) than all of the ionic media based on diatrizoate, iothalamate, iodamide, and ioxaglate. The ranges of mean C3a values generated by saline, nonionic CM, and ionic CM were 48 to 60, 65 to 173, and 807 to 3272 ng C3a/50 microL, respectively. Complement activation was found to correlate with osmolality (r = 0.945, all media) and with molarity (r = 0.994, diatrizoates).

Complement Activation↗

Effect of iodinated contrast media on the synthesis and metabolism of leukotriene B4.

To investigate whether the endogenous vasoactive substrate, leukotriene B4 (LTB4), was induced in adverse reactions observed after intravenous injection of iodinated contrast media (CM), the authors measured the in vitro production and metabolism of LTB4 by human polymorphonuclear leukocytes (PMNs) after stimulation with different doses of commercial CM preparations: iopamidol, 300 mg I/mL; iodamide, 300 mg I/mL; iohexol, 300 mg I/mL; ioxaglate, 320 mg I/mL; and the experimental preparation, iomeprolo. This study showed that the CM studied do not stimulate the production or metabolism of LTB4 by isolated human blood PMNs. All of the CM studied except iodamide do not inhibit the production or metabolism of LTB4 in PMNs stimulated by A23187. The in vitro hepatic microsomal oxidation of exogenous LTB4 to (omega-1)OH LTB4 and omega-OH LTB4 was inhibited by all the CM studied. LTB4 production by PMNs seems not to play a major role in anaphylactoid reactions observed after iodinated CM. However, a transient blockade by CM of LTB4 metabolism, leading to an increase of steady-state concentrations of LTB4, could not be excluded by these experiments.

Animals↗

Treatment of sudden deafness with sodium salts of triiodobenzoic acid derivatives.

Twenty-two patients with a complaint of sudden deafness were treated with one of the other of two radiopaque contrast media, 9 received daily doses of sodium iothalamate, and 13 were treated similarly with methylglucamine and sodium iodamide. Four of the first group and eight of the second demonstrated either an effective partial or a complete recovery of hearing function. Those failing to respond were generally classified completely deaf at admission and report nausea, vomiting, or vertigo at onset of sudden deafness. Treatment with sodium salts of triiodobenzoic acid derivatives, i.e., sodium iothalamate and methylglucamine and sodium iodamide, is judged to be effective in selected cases of sudden deafness.

Adolescent↗

[Study of interaction between contrast media and human serum albumin by the fluorescence method].

Structural changes in the human serumal albumin under the effect of roentgen-contrast media, viz. bilignost, triiotrast, endografine, iodamide, triombrine and cardiotrast, were investigated by the method of fluorescence. The complex-formation of albumin with triiodotrast, bilignost and endografine was shown to call forth a short-wave shift of the fluorescence peak by approximately 20 nm. The binding section for these substances is characterized by an association constant equalling 1.2-10(5) M-1. The authors presume that triiodotrast, bilignost and endografine cause changes in the microstructure of the aqueo-protein layer in the area of the tryptophan residue localization. As to triombine, iodamide and cardiotrast fluorescence failed to disclose their combination with the human serumal albumin.

Acetrizoic Acid↗

[Effect of x-ray contrast substances on the complement system of rats].

The purpose of the work was to demonstrate the effect of radiographic contrast media (RCM) 50% bilignost, 76% triombrast, 80% iodamide-380 on the complement system in rats. It has been found that RCM cause alternative complement activation during incubation with the whole blood or serum in vivo and in vitro. The RCM effect value depends on the drug dose and increase in the order: triombrast iodamide bilignost. Different sensitivity of animals to the effect of RCM on the complement system has been shown.

Animals↗

[Quality control in urography using non-ionic contrast media (iopamidol) and induced hydration].

A trial was carried out with the aim to overcome the limits of the non ionic contrast medium (cm) in the urographic evaluation of ureters and bladder (poor distention and high density). 200 urographies have been performed in patients with normal renal function (group 1: sodium iodamide; group 2: iopamidol; group 3: iopamidol with glucose solution; group 4: iopamidol and injection of glucose solution after 15'). The scores ascribed to the four groups have been compared: in the comparison between ionic and non ionic cm a slight advantage of iodamide is evident, particularly in the evaluation of calyces and ureters. By adding glucose solution to iopamidol after 15', an improvement in the quality of the urogram has been obtained, but not statistically significant.

Adolescent↗

Measurement of N tau-methylhistamine concentrations in urine as a parameter for histamine release by radiographic contrast media.

In a group of 750 patients who were admitted for excretory urography using iodamide, 14 distinct adverse reactions were observed. 2 of these patients exhibited a severe reaction, 4 a moderate reaction and 8 a mild reaction. In the urine portions collected 1 h after the administration of the contrast medium N tau-methylhistamine (an important histamine metabolite) was elevated both in patients showing severe adverse reactions and in those with moderate reactions. There was a rather good correlation between the increase of urinary N tau-methylhistamine concentrations and the severity of the reaction to iodamide.

Adult↗

Toxicity of X-ray contrast media in cell cultures.

Monolayer cell culture techniques for neuronal and glial cells and fibroblasts were used for the investigation of the direct toxicity of x-ray contrast media. The effect of various concentrations of sodium diatrizoate, methylglucamine salts of diatrizoate, iothalamate, iodamide, metrizamide, iocarmate, ioserate, and ioglycamate were studied. The intravenous biliary contrast medium--ioglycamate--was most toxic to all cell types. All the contrast media studied were somewhat toxic to neurons in the concentration of 50 mmol/l and showed variable glial toxicity. In equiosmolar concentrations the contrast media studied showed toxicity on neurons in the following order: iothalamate, diatrizoate, iodamide, ioserate, iocarmate, ioglycamate. Fresh metrizamide solution in equimolar concentrations showed the least toxic effects on neurons but interfered considerably with the growth and survival of glial cells. Metrizamide solution proved to be highly toxic to neurons when refrigerated for two weeks. Methylgucamine iocarmate produced a peculiar swelling of fibroblasts.

Cell Survival↗

[The effect of diagnostic contrast media on the activity of lactate dehydrogenase in rat blood].

It is shows that the diagnostic Roentgen contrast media (RCM) in a dose of 2.0 g iodine/kg increase the activity of lactate dehydrogenase in rat blood, the effect decreasing in the following order: iodamide > bilignost > triombrast > peritrast > melitrast > omnipaque > hexabrix. At the same time, the RCM in a dose of 0.5 g iodine/kg (iodine concentration, 0.03-30 mg/ml) and gadolinium-containing magnetic-resonance contrast media (MRCM) in a dose of 0.1 mM/kg (gadolinium concentration, 0.2-1 mg/ml) inhibit the enzyme, the effect decreasing in the following order: bilignost = iodamide = triombrast = peritrast > hexabrix > omnipaque = melitrast = ultravist = magnevist = dipentast. The mechanism of action of the contrast media on the LDH activity was studied and it was found that changes in the enzyme activity is correlated with the toxicity (LD 50) of RCM. The groups of risk from the standpoint of side reactions to the intravenous RCM introduction are determined.

Animals↗

[Histamine-releasing action of x-ray contrast media in rats in vivo].

The effect of roentgen contrast media (RCM)--50% bilignost, 76% triombrast, 80% iodamide-380, on degranulation of peritoneal mast cells in rats was studied. It was found that 20 minutes after intravenous injections of RCM the content of intracellular histamine significantly decreased. This effect depended on the drug dose and increased in the order: triombrast, iodamide, triiotrast, bilignost. Different sensitivity of animals to the histamine-releasing effect of RCM was detected by using the nonparametric method of mathematical statistics. The number of "sensitive" animals was 50-75%.

Animals↗

[Effect of roentgenocontrast agents on bilirubin absorption by liver sections of rats].

Spectrophotometry was employed to study the effect of radiographic contrast agents (iopanoic acid, bilimin, bilignost, endobil, biligram, verografin, iodamide) on bilirubin absorption by rat liver sections. It was discovered that lopanoic acid, bilignost, endobil, biligram, iodamide and verografin inhibit bilirubin absorption by rat liver sections by the competitiveless while bilimin by the noncompetitive mechanism.

Absorption↗

Serious or fatal complications after inadvertent administration of ionic water-soluble contrast media in myelography.

The consequences of the inadvertent administration, by the intrathecal route, of ionic contrast media instead of iopamidol in seven subjects are reported. The ionic compounds were diatrizoate, iodamide and ioxitalamate. The outcome was fatal in three out of seven subjects, and it depended on the type and the dose of the administered contrast agent. The serious or fatal reactions observed are a tragic confirmation of the predictive power of neurotoxicity data obtained in animal studies with various iodinated water-soluble compounds. The margin of safety, represented by the ratio of LD50 i.ce. in mice to clinical dose in humans, both normalized to bodyweight, appears to reliably reflect the risk of toxic reactions after intrathecal administration of iodinated contrast agents.

Adult↗

Mechanism of renal excretion of various X-ray contrast materials in rabbits.

The excretory behavior of nine nephrotropic contrast agents with varying physicochemical properties such as charge, lipophilicity, and molecular size was investigated. Renal clearance in comparison with inulin was determined by means of the continuous infusion method. Each contrast agent was infused at three dose levels in four to six rabbits. The investigations show that tubular transportation in proportion to glomerular filtration decreases with increasing dosages of all the contrast agents. Thus, with the highest concentration in plasma all contrast agents are eliminated at more or less the glomerular filtration rate (GFR). After administration of the low dosages the following differences are found: 1) Net tubular secretion increases for the monomeric contrast agent acids with increasing lipophilicity, in the order diatrizoate congruent to iothalamate less than iodamide less than acetrizoate. 2) The clearance studies do not reveal any tubular secretion or reabsorption for a hydrophilic cationic contrast agent. 3) The nonionic contrast agents do not show net secretion. The more lipophilic they are, the more they are reabsorbed. 4) Two dimeric contrast agents also do not reveal any tubular secretion. They seem to be reabsorbed more than monomers with the same charge.

Acetrizoic Acid↗

Vicarious excretion of water-soluble contrast media into the gallbladder in patients with normal serum creatinine.

Ten patients with normal serum creatinine and no evidence of acute cholecystitis were found to have vicarious excretion of water-soluble contrast media into the gallbladder 20 minutes to 72 hours after injection. Eight of the ten had unilateral renal pathology. Two patients, however, had bilaterally normal kidneys. The patients had been injected with either diatrizoate, iothalamate, or iodamide. The mechanisms and pathophysiology of vicarious contrast excretion are discussed. The vicarious excretion of intravascular contrast in the gallbladder does not in itself indicate renal or hepatobiliary disease. Although commonly associated with unilateral renal pathology, vicarious gallbladder excretion of urographic contrast may be a normal variant in some patients.

Adolescent↗

Value of high contrast medium dose in brain CT.

Fifty-five patients with brain lesions were examined by computed tomography (CT) after two doses of contrast medium: a bolus injection of 65% meglumine diatrizoate, 1 ml/kg, and a bolus injection of 65% meglumine diatrizoate, 1.5 ml/kg, in combination with an infusion of 250 ml meglumine iodamide containing 110 mg I/ml. The studies were usually performed 2 days apart and were analyzed by three radiologists. In 25 patients, one or more of the radiologists changed the diagnosis or the number or size of the lesions when the two scans were observed separately. In three patients, the primary tumor or metastases were seen in the study performed after the higher dose only, and, in two other patients having cerebral metastases, a greater number of metastases were detected in the high dose study. The lower dose containing 15 to 31 g iodine (306 mg iodine/kg) seems to be inadequate in CT of the brain.

Brain↗

Blocking effect of radio-contrast media on cochlear depression.

Furosemide injection was used in a total of 72 guinea pigs to induce a cochlear dysfunction similar to the sensorineural loss associated with sudden deafness. Prior to the furosemide administration, 38 of the animals were treated with an injection of one of four radio-contrast media; methylglucamine and sodium diatrizoate, sodium iothalamate, methylglucamine and sodium iodamide, and methylglucamine diatrizoate. In the control animals, receiving only furosemide, both endocochlear potential (EP) and cochlear microphonic (CM) underwent a severe depression followed by recovery and subsequent secondary depression. Animals pretreated with one of the first three compounds showed little or no EP or CM depression. Animals pretreated with the fourth, methylglucamine diatrizoate, showed the same EP depression as the control animals. The possible mechanism for this blocking effect and its significance in the clinical treatment of sudden deafness is discussed.

Animals↗

Replication of an avian myxovirus in tumor cell cultures obtained from effusions of mammary carcinoma patients.

In view of the possible use of viruses for the immunotherapy of breast cancer, the replication of a strain of fowl plaque virus was studied in the tumor cells of 11 mammary carcinoma patients with malignant effusions. The tumor cells were obtained by centrifugation on iodamide solutions, then cultured in vitro, and infected by a fowl plaque virus previously adapted to grow in a mammary carcinoma cell line. Virus multiplication was observed in all cases, a prerequisite for the use of autologous viral oncolysates for immunotherapy in mammary carcinoma patients.

Ascitic Fluid↗