Acta radiologica. Supplementum最新文献

All types of clinically employed iodinated roentgen contrast media (CM) cause vasodilatation after i.a. and i.v. administration, regardless of precise molecular structure. It is now apparent, however, that at iodine concentrations which provide equivalent angiographic contrast, this is significantly less with newer hexa-iodinated dimers, such as iodixanol and iotrolan, than older generations of compounds. The cellular mechanisms that underly the vasodilator effects of CM still remain to be fully elucidated but may include a) effects attributable to hyperosmolality; b) stimulation of the release of endogenous vasoactive mediators; and c) direct relaxant effects upon vascular smooth muscle. This review will discuss the possible contributions of these mechanisms to the vasodilatation observed in the clinical situation.

The detection and quantification of altered intestinal barrier function (intestinal permeability) have been addressed frequently during the last year, but the tests available for determination of intestinal permeability are both flawed and have limitations. The new water-soluble roentgen contrast media (CM) of low- and iso-osmolar type have been proposed as intestinal permeability probes. In this article this possible new application for water-soluble CM is discussed in terms of their inherent properties and the experimental and clinical results obtained so far. The 2 iso-osmolar dimers, iodixanol (Visipaque) and iotrolan (Isovist), seem to be as good as the well-documented radio-labeled permeability probe (51)Cr-EDTA in detecting injury of the intestinal mucosal barrier. The CM offer the advantage of allowing direct control of bowel wall exposure with the aid of fluoroscopy. Current permeability probes lack this quality. Iodine-containing substances may be analyzed by the rapid, simple and reliable X-ray fluorescence technique, which is suitable for application in routine clinical practice. We conclude that the new water-soluble roentgen CM have properties which may be of use in the diagnosis and quantification of altered intestinal barrier function.

Anaphylactoid reactions following administration of reontgen contrast media (CM) have occasionally been described. In this investigation, blood samples for nonallergic human volunteers were exposed to the CM iodixanol (Visipaque), iohexol (Omnipaque), ioxaglate (Hexabrix) and metrizoate (Isopaque 350). The degree of activation of the complement cascade and the amount of free histamine in the samples were estimated. By using a hemolytic assay, a dose-independent complement consumption was detected when salt-free dilutions of the CM were added to human serum. Very little complement consumption was detectable when the concentrations, indicating that in the CM solutions were adjusted toward normal plasma concentrations, indicating that the lack of salts in the CM formulations was responsible for causing the consumption of complement rather than the CM molecules themselves. By using ELISA assay for determination of the terminal complement complex (TCC), no increase in TCC level was detected following the addition of iodixanol to human serum. The results indicate that iodixanol does not activate the complement cascade when added to human serum, and that it is unlikely that anaphylactoid reactions observed in man after CM administration are caused by CM-induced anaphylatoxins. No histamine release was observed following the addition of ioxaglate, metrizoate, iohexol or iodixanol to blood from nonallergic individuals.

The intravenous use of roentgen contrast media (CM) is associated with a low incidence of renal impairment. This paper considers the intravascular handling and retention of CM in relation to effects on renal function - specifically the ability of the kidney to reabsorb and catabolise low molecular weight proteins. Renal morphology following experimental administration of a high dose of an isotonic dimeric CM (iodixanol at 3 g I/kg) in rats showed numerous, large, protein-containing vacuoles or droplets in the cells of the proximal convoluted tubule. These were fully formed within 3.5 hours. The process of vacuole-formation involving the uptake of CM appears to be analogous to dextran uptake that occurs via fluid phase endocytosis. These vacuoles or CM droplets are abundant for 7 days but then slowly decline over several weeks. The quantitative recovery of (14)C iodixanol (3g I/kg) from the kidneys between 3.5 hours to 7 days after administration was about 1% of the dose, with some 0.2% of the original dose still present at 28 days. Subcellular analysis to determine the site of the radiolabel showed that the (14)C was associated with lysosomal marker enzymes. The CM-induced vacuoles/droplets are most probably giant lysosomes, which contain the intracellularly retained CM. Co-administration of tracer doses of (125)I-labelled cytochrome C with iodixanol showed some impairment of low molecular weight protein reabsorption, but remarkably this process was not effected when the vacuoles were fully formed. The conspicuous morphology of the vacuoles, the CM retention and the transient proteinuria and enzymuria cannot presently be associated with any functionally significant impairment of tubular or cellular processes.

Since the first animal coronary arteriogram in 1933 there have been many innovations in techniques and contrast media. From 1933 through the late 1950s the procedures used involved nonselective aortic injections and the use of acetylcholine to slow the heart. The first selective coronary arteriogram in animals was performed by West, Kobayashi & Guzman in 1958 (45) and in 1959 Guzman & West (7) observed ventricular fibrillation with some media but not others. In 1967 Judkins (14) described the catheter designs for right and left coronary catheterizations that we still use today. In the 1970s and 80s many authors observed the ionic monomeric contrast media reduced plasma calcium causing fibrillation and myocardial depression. Supplementation of ionic media with calcium was shown to moderate these adverse effects. Almen's vision of low osmolality contrast media and the creation of metrizamide (1) stimulated the rapid development of monomeric and dimeric nonionic contrast media. The ionic dimeric medium ioxaglate also provided low osmolality. Digital frame grabbers and computers lead to the development of digital subtraction angiography and new applications of arteriography, frequently using dilute media. Unexpectedly, during prolonged right coronary arteriography in animals, dilute nonionic media were found to produce increased fibrillation as compared to dilute ionic media. The addition of sodium to nonionic media significantly reduced the incidence of fibrillation. Animal studies with the nonionic medium iodixanol supplemented with sodium and calcium (Visipaque) have demonstrated minimal incidences of fibrillation and myocardial depression.

The present review deals with the side-effects of contrast media (CM) on cardiac function during coronary angiography. A physiological approach is used to redefine existing concepts of CM osmotoxicity and chemotoxicity in terms of osmolal, ionic and molecular effects. The main idea conveyed is that purely ionic effects are of central importance during and immediately following the transit of a brief coronary bolus. Ionic effects result largely from rapid transient washout of normal extracellular ions, but are also influenced by ions present in the CM. In particular, the calcium (Ca) and sodium (Na) ions controlling cardiac function are easily affected. The myocardial Na-Ca exchange, which is mainly a physiological mechanism for cellular Ca efflux during cardiac relaxation, is therefore highlighted in detail. The importance of avoiding a potential Na-Ca mismatch is shown by examples from basic physiology, cardiac surgery and coronary angiography and by results of experiments with Visipaque. In the isomolal and isotonic CM Visipaque, which is based on the dimer isodixanol (320 mg I/ml), an available osmolal space is filled with an appropriately balanced supplement consisting of NaCl (19mM) and CaCl2 (0.3 mM).

The effects of the new nonionic dimeric hexa-iodinated contrast media (CM) iodixanol on renal function and morphology were investigated in 7 independent studies in rats, rabbits and monkeys and compared with other iodinated CM. No significant effect on serum creatinine levels was seen at doses up to and including 5 g I/kg in rats and 10.5 g I/kg in rabbits. An immediate and transient increase in proteinuria was found in rabbits when 10.5 g I/kg was administered as a bolus, and when 12.5 g I/kg was administered as a slow infusion in a comparative study with several CM. Increased serum elimination half-life was shown by measuring serum iodine concentrations after the infusion of 12.5 g I/kg. The effect of a high dose of iodixanol on proteinuria and elimination half-life were in this study in the same range as those of the monomeric nonionic CM, but less pronounced than those of the monomeric ionic CM. Reduced renal capacity was induced in male rats by performing unilateral nephrectomy 4 weeks before i.v. injection of iodixanol or iopamidol (2g I/kg). The administration of CM did not affect renal function monitored as serum concentrations of creatinine and urea. The vacuolation of renal proximal tubular cells and kidney iodine retention were investigated in rats 48 hours after administration of different doses of iodixanol or iotrolan. The no-effect level for vacuolation was 0.5 g I/kg for both CM. Iodine retention was higher in male than females rats, and was higher for iodixanol than iotrolan at the 2 highest dose levels (3 and 5 g I/kg). No difference in iodine retention was found at the other dose levels (0.25-1g I/kg). The reversibility of renal proximal tubular vacuolation after administration of iodixanol was studied in male rats (1.2 g I/kg) and monkeys (1.2 and 3.6 g I/kg). The vacuolation was more pronounced in rats than in monkeys. Vacuolation was completely reversed in all rats 3 weeks after dosing, and 2 of 3 monkeys 3 days after a dose of 1.2 g I/kg. The degree of vacuolation evident in renal percutaneous biopsy specimens from monkeys 14 days after i.v. administration of iodixanol at a dose of 3.5 g I/kg was not significantly different to that in control animals. In conclusion, iodixanol affected renal function to the same degree as did the nonionic monomeric and dimeric comparative media, but to a lesser degree than the ionic monomers. The degree of renal proximal tubular cell vacuolation induced by iodixanol seems to be species-dependent, being less pronounced and more quickly reversed in monkeys than rats.

Even at its highest concentration, 320 mg I/ml, Visipaque - based on the nonionic dimer iodixanol - is isoosmotic to blood plasma, whereas Omnipaque (300 mg I/ml) - based on the nonionic monomer iohexol - has an osmolality of about twice that of the plasma. However, the fact that the solution is isoosmotic to plasma does not necessarily mean that it is isotonic to plasma. An isoosmotic solution can still cause a net movement of water over the plasma membranes of, for example, erythrocytes and endothelial cells. Determination of the tonicity of Visipaque 320 mg I/ml and comparison with that of Omnipaque 300 mg I/ml and hypertonic NaCl have been performed. No change in the water content of human erythrocytes was seen after mixing whole blood 10:1 with either Visipaque 320 mg I/ml or 155 mM NaCl, whereas a significant decrease in water content occurred with Omnipaque 300 mg I/ml and 620 mM NaCl. No difference in the water content of rat erythrocytes was evident after mixing whole blood with Visipaque 320 mg I/ml or isotonic NaCl. However, as with human erythrocytes, a significant decrease in water content occurred after rat blood was mixed with Omnipaque 300 mg I/ml. In conclusion, Visipaque 320 mg I/ml does not cause any net movement of water over the human or the rat erythrocyte plasma membrane, i.e., Visipaque is isotonic to human and rat blood plasma.

Iodixanol (Visipaque) is an isotonic, electrolyte-balanced roentgen contrast medium for intravascular use. The patented and well-proven formulation and the rationale for it are described, and the efficacy and safety are documented. The stability of iodixanol is well within the specifications under all relevant conditions, both in glass and polypropylene bottles; the product has a recommended shelf-life of at least 36 months when stored at room temperature and protected from light. Heating to body temperature before use is acceptable and recommendable, and storage at 37 degress C for 1 month does not jeopardize product quality. Iodixanol has no apparent immediate in vitro incompatibility reactions with drugs often used in connection with roentgen contrast examinations.