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Purpose: To study the feasibility of using an iodinated particulate contrast agent, iodipamide ethyl ester (IDE), for angiography., Materials and Methods: IDE at doses of 40-100 mg of iodine per kilogram was diluted to a total volume of 5-20 mL and used for digital subtraction angiography in nine dogs under general anesthesia. Equivalent images were obtained by using water-soluble contrast medium (WSCM) for comparison (iohexol) in seven animals. All images were reviewed by blinded reviewers and graded subjectively on a five-point scale., Results: Angiographic studies of multiple vascular territories performed with IDE yielded images of slightly lower overall quality compared with images obtained with WSCM (P = .14, Mann-Whitney U test). Arterial phase images were subjectively superior with WSCM when compared with IDE (P < .0001, chi 2.) Depiction of the corresponding veins during the venous phase on the IDE angiograms was superior to that on WSCM angiograms in 12 of 21 cases, although this did not reach statistical significance (P > .05 chi 2). Images of the renal vein and portal vein achieved with IDE were graded as superior to those achieved with WSCM in eight of 10 reviews., Conclusion: Angiography is feasible with IDE. Compared with WSCM, IDE produced images of lesser quality during the arterial phase, but of equal or superior quality in the venous phase depending on the vessel studied. Because it is excreted slowly in bile and is isotonic, it may prove useful in patients with renal insufficiency, diabetes, multiple myeloma, or severe coronary disease.

The authors assume a new type of interaction of the aqueous X-ray contrast substance type adipiodone (Ultrabil 50% Spofa) with immunomodulators of Corynebacterium parvum (CP) and the endotoxin of Shigella dysenteriae (LPS). The fatal type of interaction developed regularly as a result of the concurrent i.v. administration of the X-ray contrast substance adipiodone with the endotoxin of Shigella dys. (LPS) to laboratory animals (mice) which had five days previously a single dose of Corynebacterium parvum (CP). The effect of the interaction was evaluated using LD50 of adipiodone (Ultrabil Spofa) which in interaction with the immunomodulators of CP and LPS was identical as the dose used in diagnostic practice. The authors considered the possible development of "oxygen stress" as a consequence interacting processes and complement activation.

Blood pressure (BP), plasma prekallikrein (PK), and the extent of activation of factor XII (XII-ACT) were studied after the intravenous injection into rats of dextran (Macrodex), the ionic radiographic contrast substance iodipamide (Biligrafin), or the non-ionic contrast substance iohexol (Omnipaque). After acetone activation plasma kallikrein was assayed as plasminogen activator, BAEe esterase or S-2302 amidase, and factor XIIa was assayed as kaolin-activated prekallikrein activator. Dextran induced a strong and lasting hypotension, preceded by significant lowerings in PK and XII-ACT. Iodipamide induced a rapid and dose dependent BP fall, no change in plasma PK, but a slightly reduced XII-ACT. Iohexol induced no significant alterations, neither in BP, nor in plasma parameters. Pretreatments of the rats with iodipamide abolished the dextran-induced reductions in PK and XII-ACT, and almost blocked the fall in BP. We conclude that the ionic contrast substance iodipamide is capable of blocking dextran shock in the rat by preventing an activation of the contact activating system in plasma.

The general, neural and cardiovascular tolerance of iotroxic acid (Biliscopin) and its deleterious effect on membranes were investigated in comparison with iodipamic- (Biligrafin), ioglycamic- (Biligram, Bilivistan) und iodoxamic acids in different experimental models. Tolerance (DL50) of iotroxic acid after i.v. injection in the rat proved to be significantly better than that of all the reference substances. The difference was most apparent in animals which had previously been given histamine. Neural tolerance was found to be best after iotroxic acid and iodipamic acid and poorest after iodoxamic acid. In in vitro investigations the erythrocyte membranes were far less damaged by iodoxamic acid and iotroxic acid than by iodipamic acid. Iotroxic acid was also particularly well tolerated after intracisternal injection and after injection into the carotid artery of the rat. The effect of iotroxic acid on the cardiovascular system of the cat was distinctly weaker than that of ioglycamic acid and, when given in high doses, evidently also weaker than that after administration of iodoxamic acid. The excellent general tolerance of iotroxic acid can be explained by the fact that its deleterious effect on membranes is less than that of iodipamic acid and that its neurotoxicity is distinctly lower than that of iodoxamic acid.

Particulate suspensions have been developed for use as contrast agents to aid in the detection of hepatic lesions by CT. In several previous rodent studies, the toxicity and tissue concentrations of iodipamide ethyl ester (IDE) particles have been evaluated. The purpose of this study was to determine the pharmacokinetics of IDE in three dogs by evaluation of CT enhancement. Serum chemistry and hematologic parameters after intravenous administration were also followed. A dose of 75 mgI/kg IDE caused an increase of 40-60 Hounsfield units (HU) in liver attenuation, which persisted from 5 minutes to ten hours postinfusion. No enhancement of tissues other than liver and spleen was observed. IDE was completely eliminated from the liver within seven days. A mild transient elevation of liver enzymes may be attributable to the use of barbiturates rather than IDE. A transient depression of the white blood count was the only biochemical or hematologic change that was clearly in response to the infusion of IDE particulates.

Iosefamate meglumine has attracted attention as a possible hepatobiliary contrast agent for CT scanning. However, its limited hepatic opacification has prevented clinical acceptance. To find a more efficient agent, the efficacy and toxicity of six derivatives of iosefamate were compared with those of the parent compound in dogs. Twenty dogs received intravenous doses ranging from 150 to 600 mg I/kg of one of these seven water-soluble, ionic, dimeric agents. Three control animals received equivalent amounts of physiologic saline. The CT densities of liver, biliary tract, kidneys, and blood were then measured for up to 3 hr. Toxicity tests of liver and kidney function were performed for up to 3 days. Among the new agents, only MI-294, a previously unreported compound, proved to be a slightly more efficient hepatic opacifier than iosefamate (0.40 vs. 0.34 H per mg I/kg, respectively). MI-294 was also the least toxic. However, transient abnormalities in at least one liver function test were observed with every agent at some dose level. One animal died with hepatic necrosis after receiving iosefamate. No renal impairment was noted in any case. MI-294 has advantages over iosefamate as a CT liver and biliary opacifier in dogs. Potential hepatotoxicity of this class of agents needs to be more fully evaluated.

Cholografin and Renografin 76 were studied to determine their effects on platelet function. In vitro platelet aggregation was significantly inhibited by at least 3.4 micron/ml Cholografin and 19.5 micron/ml Renografin 76. Patients who received Cholografin for intravenous cholangiography, and Renografin 76 for non-cardiac angiography, had low levels of plasma contrast agent, and hemostasis was clinically unimpaired. Patients who received Renografin 76 for cardiac angiography had inhibition of platelet aggregation at high levels of plasma contrast agent; there was no correlation with prolonged bleeding times, or with bleeding complications. High levels of plasma contrast agent may inhibit platelet aggregation in vitro and in vivo, although this may not be associated with clinically significant bleeding.

Iodipamide meglumine (Cholografin) has been implicated in several cases of liver injury in patients. The present study was designed to assess the hepatotoxic potential of this drug in rats. Iodipamide administered intraperitoneally or intravenously caused a characteristic type of necrosis which began in the midzonal area and spread to the centrilobular region. Only rats weighing 400 g or more developed necrosis when the dose administered was 2 mmol/kg. Rats weighing 200 g failed to develop liver necrosis even when given 3 mmol/kg. Selenium deficiency and pretreatment with 3-methylcholanthrene protected against liver necrosis due to iodipamide. Phenobarbital pretreatment provided little or no protection. Kidney tubular necrosis was also observed but occurred in young rats and in selenium-deficient rats which developed no liver necrosis. These results indicate that iodipamide is a hepatotoxin in rats. There are a number of factors, age being the most striking, that modify its hepatotoxicity.

The effect of intravenously injected iodipamide ethyl ester (IDE) particles (150 mgl/kg) on white blood cells was studied by light and electron microscopy. The clearance of IDE from rat plasma also was determined by analyzing free IDE particles in a counting chamber. The total white blood cell count remained essentially unchanged up to 40 minutes after the IDE injection, but the polymorphonuclear (PMN) neutrophil count decreased significantly. At 5 minutes postinjection, occasional PMNs contained ingested IDE particles, but by 40 minutes no intracellular particles could be found in the peripheral circulation. In vitro incubation experiments confirmed that human PMNs ingest IDE particles. In electron microscopy, the cells and particles seemed to be morphologically intact. Of the IDE particles counted at 5 minutes postinjection, only 4% remained in plasma at 30 minutes and none at 40 minutes. The decrease in PMN count apparently reflects sequestration of phagocytic cells from the circulation.

Since complement activation is sharply temperature-dependent, we have examined the effects of fever produced by a very small dose of endotoxin on contrast media lethality in rabbits. After the injection of 8.2 ml/kg of 52% methylglucamine iodipamide, a group of rabbits exhibiting an average temperature elevation of 1.5 degrees C had a 100% mortality rate. This was contrasted to a 30% mortality in control rabbits receiving contrast alone, and no mortality in rabbits receiving endotoxin alone. The rabbits with fever and increased mortality exhibited increased activation of serum complement. From this preliminary data it appears that caution should be observed in performing a contrast examination in a patient with endotoxemia and/or a fever.

Both ionic and nonionic, monomeric and dimeric contrast media were found to release serotonin from intact human platelets in vitro. The monomeric contrast media were compared at the concentration range of 25 mg I/ml. Iothalamate was the strongest and the statistically equal metrizamide iopamidol, and P-297 were the weakest releasers. Monomeric and dimeric contrast media were compared at concentration ranges of 50 and 100 mg I/ml. They ranked, in descending order of serotonin releasing potency: iodipamide, iothalamate, P-127, iopamidol, and a statistically indistinguishable group of the monoacid dimer P-286, the nonionic dimer ZK 74 435, and metrizamide. The capability of contrast media to release serotonin seems to be a composite result of their specific physical and molecular structural properties.