Effects of iodinated contrast media on endothelium: An in vitro study.

The aim of this study was to determine the influence of radiographic contrast media (CM) on endothelial cells in order to compare the effects of non-ionic (Iomeron and Visipaque) and ionic (Hexabrix and Uromiro) CM on the endothelial cells (EC). Human and murine cells were exposed for 2, 4 and 24h to increasing concentrations (12.5, 25, 50 and 100mg/mL) of test compounds. Controls were incubated with complete growth medium or mannitol solution (osmotic control). MTT assay was used to evaluate the cell viability, LDH assay was used to evaluate the membrane damage. The results demonstrate a difference between non-ionic and ionic compounds in the effect on endothelium. Ionic CM show to strongly affect endothelial cells viability under all tested conditions, while non-ionic CM show effects only after prolonged exposure at 50 and 100mg/mL, which represent instant concentrations lasting just minutes after intravascular injection of CM. Taken together, these results confirm that the currently employed non-ionic contrast media are well tolerated by the vascular endothelium and have wide margins of safety.

Reacciones adversas a medios de contraste iónicos en urografía excretora: Hospital Roosevelt, abril 1996-febrero 1997 / Adverse reactions in excretory urography using ionic media contrast, April 1996-February 1997, Hospital Roosevelt

Objetivo: Determinar cual de los medios de contraste (MC) iónicos producía con mayor frecuencia y gravedad de reacciones adversas (RA) en la urografía excretora(UE),en el Hospital Roosevelt,Guatemala, desde abril de 1996 a febrero de 1997.Material y Métodos: Se realizó un estudio prospectivo seleccionando a 200 pacientes sometidos a UE, que fueron divididos en cuatro grupos(cada uno con n=50),según el MC yodado, hidrosoluble, iónico y alta osmolaridad administrado por vía intravenosa (IV) en dosis de 80 a 100 ml:1) iodamida,2) ioxitalamato,3), amidotrizoato y 4)diatrizoato. Se incluyeron pacientes mayores de 12 años, ambulatorios u hospitalizados, sin antecedentes de RA a los MC, asma, sensibilización al yodo y sin insuficiencia cardíaca congestiva. Se clasificacon las RA en leves, moderadas y graves, según la Organización Mundial de la Salud. Se estabaleció el puntaje de gravedad(PG):RA leve=2,RA moderada=4 y RA grave=8; el PG total(PGT) y el PG promedio (PGP). La gravedad se dividió en baja, intermedia y alta. Se usó distribución de frecuencias en porcentajes y chi cuadrado con p menor o igual de 0,05(5/100). Resultados: La frecuencia de RA fue de 31/100. Leves el 93/100, las moderadas el 7/100 y no hubo graves. El 38/100 de los pacientes con iodamida tuvo RA.La frecuencia de RA de los MC tuvo un valor de p=0,713.El amidotrizoato tuvo el PGP m s alto (4,4); el ioxitalamato tuvo el PGP mas bajo (3,3). El 54/100 de los pacientes tuvo gravedad baja y el 46/100 tuvo intermedia. Discusión: La frecuencia de RA a los MC iodamida, ioxitalamato, amidotrizoato y diatrizoato en la UE fue alta, mayor que lo reportado y sin diferencias importantes entre ellos.Las RA leves fueron muy frecuentes y las moderadas raras. La ausencia de RA graves indica la seguridad de los MC. No hubo diferencias importantes en la gravedad. El PG valoró con objetividad la gravedad de las RA a los MCiónicos usados en UE

[The effect of epsilon-aminocaproic acid and prednisolone on the activation of the complement system due to x-ray contrast agents in rats in vitro]. / Vliianie épsilon-aminokapronovoi kisloty i prednizolona na aktivatsiiu sistemy komplementa, vyzyvaemuiu rentgenokontrastnymi sredstvami u krys in vitro.

epsilon-Aminocaproic acid and prednisolone in concentration of 3.0 x 10(-5) M are proven to reduce or even completely prevent activation of the alternative pathway of the component which has been induced by iod-amide adipiodone and triombrast in concentrations 2.5 x 10(-2) M in the serum of "sensitive" rats. The preventive effect of the glucocorticoid appeared less pronounced. There exists direct positive correlation between the degree of the component activation with radiopaque compounds and preventive effect of the drugs studied.

[Adverse reactions to high osmolarity contrast media. A comparative-prospective study]. / Reacciones adversas a medios de contraste de alta osmalaridad. Estudio comparativo--prospectivo.

The purpose of this study was to verify and compare the different types of reactions to iodinated contrast media available at the Social Security Metropolitan Hospital Complex: Conray 60%, Vascoray and Uromiron. These are ionic, high osmolality compounds. The authors found that, in 400 patients not only the osmolality had an important role in the reactions observed, but that the intrinsic nature of the molecule of the contrast medium used was the determining factor.

Reacciones adversas a medios de contraste de alta osmalaridad. Estudio comparativo--prospectivo / Adverse reactions to high osmolarity contrast media. A comparative-prospective study

The purpose of this study was to verify and compare the different types of reactions to iodinated contrast media available at the Social Security Metropolitan Hospital Complex: Conray 60%, Vascoray and Uromiron. These are ionic, high osmolality compounds. The authors found that, in 400 patients not only the osmolality had an important role in the reactions observed, but that the intrinsic nature of the molecule of the contrast medium used was the determining factor

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.

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).

Life-threatening arrhythmias stopped by cough.

In the course of 131 coronary angiographies, a non-ionic hyperosmolar contrast medium (Uromiro 75%, Bracco, Milano) provoked transient arrhythmias in 92 cases: 50 marked sinus bradycardias, 11 asystoles, 21 low-rate idiojunctional rhythms, 1 first-degree AV block, 7 third-degree AV blocks and 2 ventricular fibrillations. In 90 cases the rhythm disturbance was stopped by mere repeated cough. In the 2 cases of ventricular fibrillation direct current shock was used. If instructed coughing started within 8 seconds after the onset of arrhythmia, the patient maintained consciousness and the cough, as an internal cardiac massage, proved to be an adequate resuscitation method. In case prodromal signs of artificial bradycardiac arrhythmias were present, immediate cough could usually prevent the loss of consciousness and could also stop the arrhythmia. Therefore it seems logical to apply this method in patients at risk of Adams-Stokes attacks. A certain number of sudden deaths could be avoided.

[Comparison between isteropac and a new non-ionic contrast medium for hysterosalpingography (B-15000)]. / Confronto tra Isteropac e un nuovo mezzo di contrasto non ionico per isterosalpingografia (B-15000).

The authors refer the results of a double blind hysterosalpingographic study with a traditional ionic contrast medium (Isteropac) and a new non-ionic one (B-15000). Both the contrast have provided good quality images, without significant intolerance. Moreover the new non-ionic contrast medium has shown an easier utero-tubal transit with a sensible reduction of the examination length and a better diagnostic result.

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.

[Comparison of the side effects of urographic contrast media (iothalamate, diatrizoate, iodamide, iopamidol) within the scope of a CT study]. / Vergleich der Nebenwirkungen nierengängiger Kontrastmittel (Jotalamat, Diatrizoat, Jodamid, Jopamidol) im Rahmen der CT-Untersuchung.

In 1465 patients the side effects of urographic contrast media for enhancement in CT were compared. The results show that the reaction frequency with iotalamate is 5.1%, with diatrizoate 7.0% and with iodamide 8.9%, but only 0.5% with iopamidol. The number of incidents to be expected with iopamidol is one decimal place lower. Obviously this has to do with its low osmolality. On the other hand we interpret the comparatively slightly higher incidence rate when using iodamide as a result of its higher lipophilic nature.

[Abnormal renal angiograms caused by injection of contrast medium]. / Durch Kontrastmitteleinspritzung verursachte abnormale renale Angiogramme.

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.

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.

[Renal contrast radiography study in hypertensive patients: comparison of the nephrotoxicity of ionic and non-ionic contrast media]. / L'indagine contrastografica renale nel paziente iperteso: confronto della nefrotossicità tra mezzi di contrasto ionici e non ionici.

The results of a study carried out on 32 patients with arterial hypertension about nephrotoxic effect obtained with a new non-ionic contrast agent have been reported. The diagnostic approach was based on the determination of the urinary excretion of two characteristic enzymes of the proximal tubule-epithelial cells (alfa-glycosidase and gamma-glutamil-transferase) and of a microprotein (beta-2-microglobulin) filtered by glomeruli and readsorbed and catalized by epithelial cells. The method used show an increased sensitivity and reliability in the early recognition of a kidney damage as well as in the control of anatomic and functional changes, in comparison with the classic parameters (azotemia, creatininemia). The results show a significantly lower enzymuric and microproteinuric level using non-ionic contrast media, also, in the patients at relatively higher risk of kidney damage. This results should be interpreted in favour to a lower potential nephrotoxicity of non-ionic contrast media and their elective use in the patients with a higher risk of kidney damage.

Contrast-medium-induced electrocardiographic abnormalities: comparison of bolus and infusion of methylglucamine iodamide and methylglucamine/sodium diatrizoate.

A double-blind study comparing electrocardiographic (ECG) abnormalities induced by methyglucamine iodamide and methylglucamine/sodium diatrizoate was conducted in 189 patients. The media were each administered by both bolus and infusion. Iodamide caused fewer ECG changes both by injection and infusion. This contrast medium also resulted in fewer ECG changes in the patient groups with known prior ECG abnormalities, cardiovascular disease, arrhythmias, ischemia, or renal impairment and in those over 50 years of age. Digitalis did not increase the frequency of ECG abnormalities with either medium. With diatrizoate, the lower bolus dose produced as many major ECG changes in the presence of preexisting ECG abnormalities (arrhythmias, ischemia) or prior cardiovascular disease as the three-times-larger infusion dose more slowly administered; conversely, the opposite was found when renal insufficiency or older age existed. The conclusion is that iodamide media caused fewer ECG abnormalities and may be less hazardous.

[Jopamidol, a non-ionic x-ray contrast medium--tolerance from a neurological viewpoint]. / Jopamidol, ein nichtionisches Röntgenkontrastmittel--Verträglichkeit aus der Sicht des Neurologen.

A double-blind trial was carried out in 80 patients, whereby jopamidol, the first stabilized non-ionic contrast medium, and meglumine iodamine were compared in 40 patients undergoing cranial computed tomography and 40 patients subjected to cerebral angiography. There was no difference in the quality of the radiographs. Jopamidol was better tolerated and caused significantly fewer side effects or complications than meglumine iodamine. Our evidence suggests that jopamidol has significant advantages over currently employed contrast media for cranial computed tomography and cerebral angiography.