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Evaluation of various contrast agents for improved arthrography.

In the canine knee joint the monomer methylglucamine iothalamate, the dimer methylglucamine iocarmate, and the nonionic contrast agent metrizamide were examined for use in arthrography. A total of 104 injections were performed with equal iodine concentrations (280-282 mg/ml) and volumes (4 ml) of the three contrast agents. These were evaluated using radiographic comparison and iodine estimations of the joint fluid at various times after injection. Radiographically the dimer was superior, followed by metrizamide and then the monomer. The greatest amount of total iodine within the joint fluid at various times after injection was found with the dimer. Iodine concentrations in the joint fluid were similar for the dimer and metrizamide, both greater than with the monomer.

Animals↗
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Iothalamate ethyl ester as hepatolienographic agent.

In search of a hepatolienographic agent, the iothalamate ethyl ester particulate suspension was prepared with the average particle size of 1.5 mu in diameter. When mixed with plasma of different animal species, the physical properties of the particular suspension changed significantly. The nature of this difference is not understood but is probably related to protein-particle interaction in the different species. Doses of 550 mg iodine per kg body weight as a single intravenous infusion of the particulate suspension resulted in satisfactory opacification of liver and spleen in rats, followed by complete loss of radiopacity within three days. Larger doses resulted in the death of the rats within 12-14 hours. In general, the mice tolerated larger doses than rats, but there was very poor opacification of the liver, despite good opacification of spleen. Further work is being carried out to improve the suspension and to better understand the difference in behavior of the particulate suspension in different animal species.

Animals↗
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Urographic excretion studies with metrizamide and "Dimer": a high dose comparison in dogs.

Metrizamide, a new non-ionic, triodinated contrast agent has been considerable for intravenous urography. Theory predicts that lower osmotic diuresis with this agent should lead to higher urinary iodine concentrations than with ionic agents, at equivalent iodine doses. However, a distinct advantage with metrizamide has not been observed with doses of 175 mgI/kg or less. In this study metrizamide and sodium locarmate were given intravenously to dehydrated dogs at a dose level of 600 mgI/kg. During the studies the concentrations and outputs of major urinary solutes were compared. Comparisons of urinary iodine concentrations and outputs showed that at this dose the predicted advantage with metrizamide can be observed.

Animals↗
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Why does kidney size change during I.V. urography?

Meglumine iothalamate (280 ml I/ml) and sodium iothalamate (400 mg I/ml) in doses of 700 mg I/kg bw, were injected i.v. as a bolus in dogs. Renal size, urine flow rate, arterial pressure, renal blood flow and mean transit time and renal blood volume were measured before and after injection. All changes were qualitatively and quantitatively identical for both drugs. They produced a small transient renal shrinkage followed by a greater and prolonged renal enlargement. During the period of renal enlargement, urine flow increased. The time course of the enlargement paralleled the increase of urine flow rate. Renal blood flow also increased but both the mean transit time and renal vascular volume decreased. Therefore, the kidney size increase after i.v. injection of large doses of urographic contrast media cannot be attributed to an increased volume of the vessels. Most likely it is caused by diuresis-induced increase in the volume of the tubules.

Animals↗
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Fluid compartment distribution of intravenous iothalamate in the dog.

The distribution of 125I iothalamate between the intravascular and extravascular fluid compartments was determined after intravenous injection in dogs. Simultaneous measurements of total blood volume, blood iothalamate concentrations and urinary iothalamate excretion were made and permitted calculation of extravascular iothalamate. The drug diffused very rapidly to the extravascular space: more than half had reached the extravascular space one minute after injection. The ratio of extravascular to intravascular iothalamate rose to a plateau of 6.8. We conclude that the contrast material responsible for tissue opacification during radiography is primarily extravascular and that the levels of contrast in plasma during urography are affected less by renal excretion than by distribution between fluid compartments.

Animals↗
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Gated computed tomography of the human heart.

Production of in vivo images of the human heart, with delineation of the individual cardiac chambers and myocardial wall thickness, was accomplished by coupling a relatively simple electrocardiographic gating device to a translate-rotate type of computed body tomographic scanner. Differentiation between the myocardial wall and the intracardiac blood pool was attainable in the patient with a normal hematocrit only when intravenous iodinated contrast media was used.

Adult↗
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Histologic effects of Amipaque (metrizamide) and various contrast media on mouse peritoneum.

The histologic effects of Amipaque and various commonly used contrast media on mouse peritoneum were studied by intraperitoneal injections of Amipaque 370 mg I/ml and 170 mg I/ml, Conray 300 mg I/ml, Conray Meglumine 282 mg I/ml, Urografin 60% and 76%, Gastrografin and barium sulfate. Amipaque and the other water-soluble media cause no deleterious effects, whereas barium sulfate evokes granulomatous inflammatory reaction. Amipaque is suitable for gastrointestinal studies when leakage into the peritoneal cavity is expected.

Animals↗
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Urographic excretion studies: preliminary results with a six-iodine, singly-ionizing sodium salt--P.286.

Preliminary results of comparative studies with a new water-soluble contrast agent are described. The new agent, with the code P.286, is a molecule with 6 iodine atoms attached and only one ionizing group. The sodium salt of the new agent has been compared with sodium iothalamate and metrizamide in dogs. The results suggest that the sodium salt of P.286 is superior in terms of urinary iodine concentration to both sodium iothalamate and metrizamide.

Animals↗
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Sequential changes in the CT numbers of the normal canine kidney following intravenous contrast administration. I. The renal cortex.

Using a 30-second computed tomography (CT) scanner, the sequential changes in CT numbers of the kidney were determined in three healthy dogs after intravenous administration of sodium and meglumine diatrizoate and iothalamate. For all contrast media, the mean CT number of the cortex was greatest within 2 minutes of rapid intravenous administration. At doses comparable to those used clinically, a linear relationship was demonstrated between the amount of iodine administered (in mg/kg body weight) and the corrected peak mean CT number of the cortex, such that doubling the amount of iodine caused the corrected peak mean CT number of the cortex to approximately double. Following the peak, the mean CT number of the cortex gradually declined. For all contrast media, the corrected mean CT number to corrected peak mean CT number ratios at 5, 10 and 20 minutes were 58 +/- 3%, 39 +/- 3%, and 28 +/- 5% respectively. Our data suggest that rapid-sequence CT may be a valuable tool for evaluating the physiology of renal contrast media excretion.

Animals↗
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Protein binding to iothalamate ethyl ester.

A major problem in the development of a particulate hepatolienographic agent is the prevention of particle aggregation upon contact with blood. When iothalamate ethyl ester, a particulate suspension for potential use as an hepatolienographic agent, was mixed with human or animal plasmas, it resulted in moderate to severe flocculation. In a study conducted to define the binding of plasma proteins to the iothalamate ethyl ester particles, plasma was reversibly adsorbed to various particle preparations. Fractions obtained by incubation of the particle-plasma complexes in buffers of increased ionic strength and decreased pH were subjected to polyacrylamide disc gel electrophoresis. The fraction containing the specifically bound proteins produced three distinct bands corresponding to prealbumin, albumin, and fibrinogen. Since the particles flocculated only when mixed with plasma, it is postulated that the fibrinogen-particle interaction is a major factor leading to particle agglutination.

Blood Proteins↗
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Cardiovascular effects induced by the injection of a new nonionic contrast medium (Iopamidol): experimental study in dogs.

The hemodynamic effects induced by the injection in the pulmonary artery of the new nonionic water soluble contrast medium Iopamidol were compared with those obtained by the injection of two other currently used contrast media (meglumine diatrizoate and sodium iothalamate). The experiments were carried out in nine mongrel dogs. Hemodynamic variables were continuously measured prior to, during, and for 8 minutes after injection of the contrast media. Injections of iopamidol produced significantly smaller decreases in aortic pressure (p less than 0.01), contractile indices (p less than 0.01), and peripheral resistances (p less than 0.01), and changes in heart rate and in cardiac output were less pronounced. At 3-4 minutes after injection, an increase in Vmaxd was observed with all three contrast media, but it was significantly lower after injecting Iopamidol. The role of hyperosmolality in causing cardiovascular changes is discussed. The less significant changes induced by Iopamidol appear to be the result of its lower osmolality, which is about a third that of meglumine diatrizoate or sodium iothalamate.

Animals↗
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Isolated microperfused tubule model to evaluate contrast media transport in normal and occluded renal tubule segments.

We evaluated tubular handling of urographic contrast media in normal and obstructed states by the use of a model which allowed direct evaluation of transcellular flux. Segments of rabbit renal tubule were harvested by microdissection. Individual tubular segments were cannulated by micropipette while immersed in a serum bath. Radioactive iodine-labeled sodium iothalamate was added to the perfusate of normal and distally obstructed nephron segments. Any iothalamate that moved through the tubule wall was recovered in the bath. The tubular epithelium was counted to determine epithelial concentration of iothalamate. A small efflux of contrast medium occurred which was unaffected by acute obstruction and increased pressure. Proximal straight tubules were more permeable to sodium iothalamate than cortical collecting tubules.

Animals↗
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Effect of B-15,000 (Iopamidol), a new nonionic contrast agent, on cardiac function of the isolated rat heart.

The isolated rat heart model was used to examine the effect of a new nonionic contrast agent, B-15,000 (Iopamidol), on cardiac function. Comparative studies were performed with Amipaque, Renografin 60, Renografin 76, and Vascoray. The three ionic contrast agents had significantly greater detrimental effects on cardiac function than either nonionic agent. The results support the continued evaluation of the nonionic agents for use in coronary angiography.

Angiography↗
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Direct myocardial effects of intracoronary administration of new contrast materials with lost osmolality.

The effects of LV dynamics of the intracoronary administration of three new contrast materials with reduced osmolality were compared with those of a monomeric ionic material, sodium iothalamate, and the nonionic material, metrizamide. In eight anesthetized dogs, the monacid dimer, P286, caused increases in LV dimensions and decreases in LV systolic pressure and parameters of the contractile state. The changes were less than those caused by sodium iothalamte. The alterations in LV function tended to be greater, but not significantly so, during systemic hypoxemia compared to the normal state. The nonionic materials, P297 and iopamidol, like metrizamide, caused no deleterious effects on LV dynamics in either the normal or hypoxemic state. Nonionic materials actually caused a slight increase in parameters of the LV contractile state.

Animals↗
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Comparison of iopamidol, ioxaglate, and diatrizoate during coronary arteriography in dogs.

Iopamidol and ioxaglate are two new contrast media which have an osmolality approximately half that of diatrizoate for the same iodine concentration. These three contrast media were compared with each other and with Hartmann's solution during coronary arteriography in dogs using hemodynamic and electrocardiographic parameters in addition to coronary venous sinus sampling to measure changes in osmolality, electrolyte, and contrast media concentration. Iopamidol and ioxaglate had similar, but less toxic, effects in comparison with diatrizoate. These new contrast media may offer a reduction in the morbidity and mortality of coronary arteriography.

Animals↗
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Liver toxicity of ionic (Diatrizoate) and nonionic (C-29) contrast materials: effects of serum enzymes after hepatic artery injection in the rat.

Catheters were placed in the retrograde direction in the surgically exposed gastroduodenal arteries of rats. There was an early postoperative mortality of one-third of the animals. The catheter was exteriorized at the tail and was used for arterial perfusion of the liver with one experimental, nonionic contrast medium (C-29) and one ionic contrast medium (diatrizoate). Both contrast media (370 mg I/ml) were injected in a dose of 4 ml/kg rat. The contrast medium injections caused no significant changes in serum levels of the enzymes ALAT, ASAT, or GT.

Angiography↗
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Particulate contrast media for computed tomographic scanning of the liver.

A contrast agent that is selectively accumulated in the liver should greatly improve the diagnostic value of contrast enhanced CT scanning. The advantages and disadvantages of different classes of hepatographic agents are briefly reviewed. Experimental results obtained with the particulate contrast agents, iothalamate ethyl ester and iodipamide ethyl ester, are presented in more detail. Following intravenous infusion of iodipamide ethyl ester, approximately 60% of the injected dose is accumulated in the rat liver. CT scanning experiments involving iothalamate ethyl ester infusions in New Zealand White rabbits demonstrate significantly higher liver contrast enhancement at 10-30 minutes postinfusion than is observed with diatrizoate at a sixfold greater iodine dose. The selective accumulation of a particulate contrast agent in hepatic reticuloendothelial cells compared to virtually no accumulation in implanted VX2 carcinoma demonstrates the important potential value of these agents in improving detection of liver metastases.

Animals↗