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PubMedDate not supplied

Contrast enhancement pharmacokinetics of six ionic and nonionic contrast media.

The contrast enhancement of six contrast media (CM) was compared in 13 tissues of the rat after rapid intravenous bolus injection. The rats were sacrificed at 0 and 40 seconds and 2, 5, and 15 minutes after contrast injection. 125I labeled diatrizoate, metrizamide, ioxaglate, iohexol, iopamidol, and a nonionic dimer, iodecol, were each injected at a dose of 612 mg iodine per kg body weight, and iodine concentration (IC) and contrast enhancement were calculated from radioactivity measurements. Higher blood IC values were obtained with the nonionic CM; similar enhancement patterns were seen in the spleen, heart, lungs, and brain. Renal IC was directly related to the number of iodine atoms per ion or molecule of CM. In consequence, renal IC was inversely related to the CM osmolality, but no such correlation was seen with the blood IC. Metrizamide produced the greatest IC in the organs of the gastrointestinal tract. There was no apparent correlation of IC with molecular structure of physicochemical parameters of the CM in any of the other tissues studied.

Animals↗
PubMedDate not supplied

Scanning electron microscopic (SEM) studies on the effect of x-ray contrast media on aortic endothelium in the rat.

A study comparing the effects of diatrizoate, ioxitalamate, metrizamide, ioxaglate, and a 22% sorbitol on aortic endothelia of the rat was performed. In each case 1 ml of the respective solution was injected in a single dose into the aorta. Endothelial damage was seen after injection of metrizamide, diatrizoate, and ioxitalamate. After injection of ioxaglate or sorbitol, only minor endothelial changes were observed.

Animals↗
PubMedDate not supplied

Functional imaging of the liver. New information from dynamic CT.

In order to assess their potential usefulness in conjunction with dynamic CT scans of the liver, functional images of several variables related to blood flow were created from dynamic CT scans of 15 patients with a variety of liver diseases. Seven of the patients received intra-arterial and intravenous boluses of contrast; the other eight received intravenous boluses alone. Intra-arterial contrast injections yielded superior functional images, but useful functional images could also be created from studies with intravenous boluses. Although respiratory motion artifacts caused some problems, images that can be interpreted in terms of effective distribution volume, transit time, and blood flow were successfully created. Functional imaging of the liver can provide a useful display of regional physiologic differences.

Breast Neoplasms↗
PubMedDate not supplied

Dynamic CT of liver cirrhosis.

Time-density curves of the liver and spleen from dynamic CT-scans, performed on ten patients with liver cirrhosis and 15 patients with fatty liver were compared with 41 normal cases. After the intravenous bolus injection of urographic contrast medium (18.5 g I), six scans per minute for 2 minutes and single scans at 3, 4, and 5 minutes were executed. In patients with fatty liver the curves of the liver and spleen did not differ from those in the normal patients. In liver cirrhosis the peak contrast enhancement of both liver and spleen was lower and delayed and the washout phases slower. The results indicate that the patterns of the time-density curves of the liver and spleen may contain diagnostic information in liver cirrhosis.

Adult↗
PubMedDate not supplied

Comparative evaluation of the effects of an ionic vs. a nonionic contrast medium on the venous endothelium. Preliminary scanning electron microscopic observations.

Isolated segments of the right jugular veins of six mongrel dogs were exposed to solutions of 60% diatrizoate (3 dogs) and 60% iopamidol (3 dogs) in vivo. Normal blood flow was re-established after 3 minutes of exposure to the contrast material. The left jugular veins served as controls. Veins were harvested at 1, 24, and 48 hours and studied by light and scanning electron microscopy. Changes consisting of cellular swelling, denudation, platelet aggregation and fibrin deposition were uniform and prominent with diatrizoate. Response to iopamidol was minimal consisting only of cellular swelling. The study suggests that post-phlebographic thrombophlebitis may be reduced by the use of nonionic contrast materials.

Animals↗
PubMedDate not supplied

New contrast agents. Chemistry and pharmacology.

Over the last two or three years, a considerable and almost universally favorable experience has been obtained in Europe with the low osmolality contrast agents. These agents, such as Hexabrix, iohexol and iopamidol have been shown to reduce the subjective pain and heat sensation associated with hyperosmolar agents. Hexabrix, although an ionic agent, has achieved a slightly greater reduction in osmolality than other low osmolality contrast agents. Low osmolality media have shown reduced chemotoxic effect on red cells, less histamine release, fewer electrocardiographic changes, and less marked hemodynamic changes compared with conventional agents. The new contrast media may be predictably safer, especially for high risk patients.

Chemical Phenomena↗
PubMedDate not supplied

Clinical comparison of Hexabrix, iopamidol, and Urografin-60 in whole body computed tomography.

Urografin 60, iopamidol and Hexabrix were studied in patients undergoing body CT scans to examine the pharmacodynamics of these contrast agents. Immediately following rapid injection, the lower osmolality media, Hexabrix and iopamidol, gave greater aortic concentration of iodine in addition to higher concentrations in the liver and spleen. These two agents also provided significantly better renal enhancement than Urografin 60, with Hexabrix giving higher levels than iopamidol. The higher early vascular concentrations of Hexabrix and iopamidol and the relative absence of side effects due to hyperosmolality and decreased toxicity may have advantages in dynamic CT scanning.

Contrast Media↗
PubMedDate not supplied

Pathogenesis of postmyelographic arachnoiditis.

The causal relationship between a myelogram with an aqueous contrast medium and postmyelographic arachnoiditis has not been clarified. Primates after myelography with metrizamide or meglumine iocarmate were studied with fluorescent microscopy, energy dispersion analysis and with scanning and transmission electron and light microscopy. All controls and, up to the eighth day after myelography, all treated animals had normal-appearing arachnoid membranes by microscopy. After eight days the treated animals had progressively more severe arachnoid fibrosis. Energy dispersive analysis revealed iodine in the arachnoid only up to 24 hours after myelography. Fluorescent microscopy revealed no evidence of immune complexes in the arachnoid. The chronic effects of water-soluble media on the arachnoid are not apparently mediated by contrast medium persisting in the arachnoid or by immune complexes.

Animals↗
PubMedDate not supplied

Development of nonionic contrast media.

In this brief history, the author reviews the observations that led to his developing a nonionic contrast medium. Current knowledge suggested that if a water-soluble medium could be made isotonic to human plasma, it would cause less pain and toxicity than the ionic media then in use. The principles and design of such a medium are discussed, as well as the subsequent chemical development and testing in animal models of first generation (metrizamide) and second generation (iohexol) nonionic media. Iohexol, which is described as a nonionic, monomeric ratio 3 contrast medium, was selected for clinical testing from among competing substances due to its low toxicity in a number of animal models. The results from these experimental models predicted that iohexol would cause fewer and less severe adverse reactions in clinical use than ionic ratio 1.5 media.

Animals↗
PubMedDate not supplied

Iohexol vs. iopamidol for myelography.

Three hundred sixty-three patients undergoing myelography were examined on a random basis with either iohexol (179) or iopamidol (184). All patients underwent neurologic or psychological assessment before and after the examination; 100 patients also submitted to cardiovascular and hematologic tests. Sixty patients were examined with electroencephalography before and after myelography. Incidence and severity of side effects were carefully evaluated in all patients and, wherever possible, by an independent observer, who was not told which contrast medium had been used. Radiographic quality was independently estimated and graded and was equally adequate with both media. Both iohexol and iopamidol will, in competent hands, provide myelograms of good radiographic quality without producing any permanent adverse sequelae. Incidence and severity of adverse side effects were slightly but significantly less with iohexol than with iopamidol. Three patients of the 25 examined with iopamidol showed EEG evidence of neuronal excitability following myelography. None of the 35 examined with iohexol showed this change.

Adolescent↗
PubMedDate not supplied

Chemotoxicity of contrast media and clinical adverse effects: a review.

The clinical effects of contrast agents not only result from high osmolality, but also from their own specific pharmacology, which mediates chemotoxic effects. In this review, the chemotoxic effects of the new nonionic agent, iohexol, are compared with those of standard ionic and other low osmolality contrast agents, ionic and nonionic. Iohexol has the lowest chemotoxicity of any agent yet synthesized. Its low systemic toxicity is the combined result of low chemotoxicity and low osmolality. Mechanisms of severe adverse reactions are reviewed, including the views of Lasser and Lalli, and the view that emphasizes the importance of cardiotoxic and hemodynamic effects. It is concluded that whichever view is taken of the mechanisms of severe adverse reactions, the new nonionic agents are likely to be safer than the ionic agents now in use.

Anaphylaxis↗
PubMedDate not supplied

Peripheral hemodynamic effects of intraventricular and intracoronary contrast media in man.

The effects of intraventricular and intracoronary contrast media on the peripheral arterial and venous beds were directly measured with forearm plethysmography. Standard dose intraventricular radiographic contrast produces a potent peripheral arterial vasodilator effect accompanied by a hypotensive and tachycardic response, followed by peripheral venoconstriction, suggesting that the net hemodynamic response is mediated peripherally. Coronary arteriography is associated with a differing pattern of response, suggesting that the most important hemodynamic effects are mediated via myocardial depression with secondary peripheral vascular responses. Hemodynamic changes occur earlier than those following ventriculography and reflect peripheral arterial and venous constriction. Dose and osmolarity of the contrast are important determinants as well as the site of administration.

Contrast Media↗
PubMed1985

Comparison of diatrizoate, iopamidol, and ioxaglate for arterial portography. An experimental study in normal dogs and dogs with portal hypertension.

Diatrizoate, iopamidol and ioxaglate were compared in five normal dogs and in five dogs with presinusoidal cirrhosis and portal hypertension for arterial portography. After selective injection of 40 ml of each contrast agent in iodine concentrations of 320 mg per ml into the superior mesenteric artery, portal vein blood samples were collected in 2-second intervals and the iodine concentrations determined using x-ray energy spectrometry. The highest iodine concentrations in the portal blood were found in both normal portal pressure and portal hypertension with ioxaglate, followed by iopamidol and diatrizoate in this order. Compared with diatrizoate, ioxaglate and iopamidol increased the peak portal blood iodine concentrations 45% and 22%, respectively. The use of ioxaglate in arterial portography should show the portal system at least as well as when a conventional contrast agent is used together with a vasodilator such as tolazoline.

Animals↗
PubMed1985

In vitro testing for the risk of arachnoiditis from myelographic contrast media.

The risk of arachnoiditis from aqueous myelographic contrast media has been assayed reliably only in experimental animals. The effect of contrast media on protein and collagen production by fibroblasts in vitro was studied. Iocarmate, metrizamide, and iopamidol added to the culture medium caused cells to produce more protein and collagen. The degree to which the contrast medium stimulated collagen production correlated with the risk of arachnoiditis from the intrathecal use of the contrast medium. In vitro testing appears to be an effective assay for arachnoiditis.

Arachnoiditis↗
PubMed1985

The use of programmed electrical stimulation to assess the fibrillatory propensity of ionic and nonionic contrast media.

Coronary angiography occasionally results in ventricular fibrillation. To compare the fibrillatory propensity of conventional ionic and nonionic contrast media, we measured QT intervals and performed programmed electrical stimulation during intracoronary injection of Renografin 76 (R76), Hypaque 76 (H76), and iopamidol (IOP) in 16 open chest dogs. In ten dogs the incidence of ventricular fibrillation following induction of a single premature ventricular beat after every fourth atrial paced beat was 19/20 with R76, 8/20 with H76, and 0/20 with IOP (P less than .001). When two premature beats were induced, the incidence of ventricular fibrillation was 20/20 with R76, 19/20 with H76, and 1/20 with IOP (P less than .001). In six additional dogs, the mean prolongation of the QT interval was 170 +/- 20 msec with R76, 105 +/- 14 msec with H76, and 63 +/- 9 msec with IOP (P less than .001). Thus, programmed electrical stimulation readily induces ventricular fibrillation during intracoronary injection of conventional ionic contrast media. The incidence of ventricular fibrillation parallels the amount of QT interval prolongation produced. H76, which lacks EDTA and sodium citrate, is less fibrillatory than R76. However, the nonionic medium IOP appears far less fibrillatory than either R76 or H76.

Angiography↗
PubMed1985

Comparison of diatrizoate, iopamidol, and ioxaglate for the contrast enhancement of experimental hepatic tumors in CT.

The accumulation of diatrizoate and two new low osmolality contrast agents, iopamidol and ioxaglate, was investigated in three experimental tumors (a well differentiated mammary adenocarcinoma, a poorly differentiated colon carcinoma, and a hepatoma) in the rat. All three tumors were implanted into the liver 12 to 14 days prior to intravenous injection of the contrast agents in a dose of 300 mg iodine per kg. Iodine concentrations were determined in blood, liver, and tumors at 1, 5, 10, and 30 minutes using x-ray energy spectrometry. Ratios between tumor iodine and blood iodine concentrations increased more with time with diatrizoate than either iopamidol or ioxaglate and were at 30 minutes significantly greater for diatrizoate than the other two agents. This suggests that the contrast medium efflux from the vascular compartment into the extravascular compartment of all tumors is greater for diatrizoate than either iopamidol or ioxaglate. Although it is known from clinical experience that the differential enhancement between hypodense hepatic tumors and liver parenchyma decreases rapidly with time after contrast administration, this investigation suggests that the substitution of diatrizoate by either iopamidol or ioxaglate should not affect appreciably the contrast enhancement in this condition in dynamic CT completed within the first minutes after contrast administration. In a later phase, after contrast administration, however, both iopamidol and ioxaglate should conceal hypodense hepatic tumors less than diatrizoate.

Adenocarcinoma↗
PubMed1986

Urography with a low osmolality contrast agent. Comparison of Hexabrix with Conray 325.

A double-blind, parallel group comparison study of Hexabrix and Conray 325 for adult intravenous urography was performed. Sixty patients with a mean age of 54 years were included. Doses of contrast ranged from 0.5-1.1 ml/kg for both groups with a mean of 0.7 ml/kg. Hematology, urinary and biochemical laboratory tests were performed prior to the study in all patients and at 24 hours afterward in nearly half the group. Biochemical laboratory tests were done at 72 to 96 hours in approximately one third of the patients. Hexabrix proved satisfactory for standard urography at a chosen dose of 16 g of iodine (50 ml). There were no statistically significant differences in the diagnostic quality of the urogram in the two groups except for bladder filling. The decreased osmotic diuresis associated with Hexabrix necessitated delayed bladder filming for optimal evaluation. Excellent patient tolerance was achieved with less pain on injection with Hexabrix. There was one death in the Hexabrix group in a patient with multiple medical problems. Although the patient's medical problems appeared well controlled and did not meet specific rejection criteria, they almost certainly played a role in his death. Hexabrix may be useful for adult urography at a lower dose range, eg, 16 g iodine, than is typically used, which also may be cost effective (competitive) given the higher projected cost of the new low osmolar agents.

Adolescent↗
PubMed1986

Effects of radiographic contrast media on monolayer cell cultures.

The relationship between iodine concentration, osmolality, and toxicity for nine different contrast media was studied. High osmolal conventional ionic contrast media (Na-metrizoate, Na-iothalamate, meglumine/Na-diatrizoate, meglumine-calcium-metrizoate) and the new low osmolal nonionic (Metrizamide, iopamidol, iohexol) and ionic dimer (Meglumine/Na-ioxaglate) contrast media were tested. Monolayer cell cultures of human cervical carcinoma in situ cells were used as a test system. The toxicity of contrast media on cell cultures was strongly dependent on the osmolality, and different contrast media with the same osmolality had about similar effects on the cell cultures. However, contrast media seem to have some additional and more specific effects since equiosmolal saline and mannitol were better tolerated. When the toxicity was related solely to iodine concentration it emerged that the new low osmolal contrast media were much better tolerated than the high osmolal conventional contrast media.

Carcinoma in Situ↗