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Ionic radiocontrast inhibits endothelium-dependent vasodilation of the canine renal artery in vitro: possible mechanism of renal failure following contrast medium infusion.

To determine if radiocontrast impairs vascular relaxation of the renal artery, segments (4-5 mm in length) of canine renal artery were suspended in vitro in organ chambers to measure isometric force (95% O2/5% CO2, at 37 C). Arterial segments with and without endothelium were placed at the optimal point of their length-tension relation and incubated with 10 microM indomethacin to prevent synthesis of endogenous prostanoids. The presence of nonionic radiocontrast (iohexol, Omnipaque 350, 1 ml in 25 ml control solution, 4% (v/v)) did not alter endothelium-dependent relaxation to acetylcholine in rings precontracted with both norepinephrine and prostaglandin F2alpha (N = 6). When the rings were precontracted with prostaglandin F2alpha, the presence of ionic contrast did not inhibit the relaxation of the arteries. However, in canine renal arteries contracted with norepinephrine, the presence of ionic radiocontrast (diatrizoate meglumine and diatrizoate sodium, MD-76, 1 ml in 25 ml control solution, 4% (v/v)) inhibited relaxation in response to acetylcholine, sodium nitroprusside (N = 6 in each group), and isoproterenol (N = 5; P < 0.05). Rings were relaxed less than 50% of norepinephrine contraction. Following removal of the contrast, vascular relaxation in response to the agonists returned to normal. These results indicate that ionic radiocontrast nonspecifically inhibits vasodilation (both cAMP-mediated and cGMP-mediated) of canine renal arteries contracted with norepinephrine. This reversible impairment of vasodilation could inhibit normal renal perfusion and act as a mechanism of renal failure following radiocontrast infusion. In the adopted experimental protocol the isoproterenol-induced relaxation of renal arteries precontracted with norepinephrine was more affected, suggesting a pivotal role of the cAMP system.

Acute Kidney Injury↗

Drip infusion urography with meglumine iodamide.

In a double-blind study of 283 patients (140 given iodamide and 143 diatrizoate), meglumine iodamide 24% produced a significantly greater degree of opacification than meglumine diatrizoate 30% (P less than 0.01 to P less than 0.001) in the renal calyces during the early phase of drip infusion pyelography. The agents were infused at a dose of 4.5 ml/kg, up to a maximum volume of 300 ml, over a period of about 10 min. The incidence and nature of laboratory abnormalities and clinical adverse reactions produced by the drugs were similar. No severe reactions occurred. The apparent superiority of the iodamide solution in the early stage of excretion, despite its lower iodine content, may be due to the partial secretion of iodamide by the renal tubules, as observed in other studies.

Adolescent↗

Contrast enhancement in abdominal CT: bolus vs. infusion.

The accuracy of in vivo iodine estimations by CT in the aortic blood was determined in the dog. Iodine wash-out curves of five patients each receiving either a bolus of 100 ml diatrizoate 60% or a 10 min infusion of 300 ml diatrizoate 30% and 138 nonenhanced abdominal CT scans with various lesions in 104 patients were analyzed. This investigation suggests: (1) In vivo estimations of iodine concentrations are subject to considerable variation. (2) Iodine accumulation and wash-out for a given contrast administration mode are similar in liver, spleen, and pancreas with tissue iodine concentrations always below blood iodine concentrations, while a significant iodine concentration above iodine blood levels is found in the renal parenchyma. (3) If contrast enhancement is analyzed separately for bolus effect (arteriovenous iodine difference [AVID] greater than 30 H), nonequilibrium phase (AVID 10-30 H) and equilibrium phase (AVID less than 10 H), a good correlation between aortic blood and tissue iodine concentration is found for the latter two phases in the kidney, liver, and spleen which is independent of the contrast administration mode. (4) Visualization of all focal (cystic and solid) lesions is improved in the kidneys after contrast enhancement, while in the other investigated abdominal organs only cystic lesions are always better visualized on the enhanced scan regardless of contrast material dose, administration mode, and time of scanning. (5) Improved visualization of a solid lesion in liver, spleen, and pancreas is most likely achieved by scanning during bolus effect and the nonequilibrium phase, that is, within the first 2 min after a contrast material bolus or during a contrast material infusion. The chance to conceal a lesion in these organs increases significantly when performed at a later stage after contrast administration, that is, in the equilibrium phase.

Animals↗

Contrast enhancement of hepatic tumors in CT: comparison between bolus and infusion techniques.

Pre- and postcontrast CT scans of 125 nonselected patients with histologically verified hepatic neoplasms were analyzed. Sixty patients received an intravenous bolus injection of 50-100 ml diatrizoate 60% in 10-20 sec, and 65 patients an intravenous infusion of 300 ml diatrizoate 30% in 5-10 min. Compared to the precontrast examination, a significant improvement in the visualization of hepatic tumors was obtained with both contrast administration methods when the patients were examined before the equilibrium phase (difference in blood iodine concentration between aorta and inferior vena cava of less than 10 H) is reached. The equilibrium phase is reached 2 min after a contrast material bolus and with termination of an infusion. Scanning in the equilibrium phase does not significantly improve visualization of hepatic tumors when compared to the precontrast examination and carries a considerable risk of partial to complete tumor concealment. For similar reasons, concealment of hepatic tumors might also result when intravenous contrast material is used for another radiographic study preceding the CT examination.

Contrast Media↗

Value of brominated fluorocarbons for the radiographic diagnosis of small-bowel obstruction: comparison with other contrast agents in rats.

OBJECTIVE: The disadvantages of water-soluble gastrointestinal contrast agents include high osmolality, contrast dilution, and severe toxicity if aspirated. Perfluorocarbons are nontoxic in the lung and peritoneal cavity. Because perfluorocarbons are immiscible with water, they have no osmotic effect and cannot be diluted. Because these properties offer theoretical advantages over traditional gastrointestinal contrast agents, we compared two perfluorocarbons with barium and ionic and nonionic iodinated contrast material in a rat model of small-bowel obstruction. MATERIALS AND METHODS: Twelve groups of six rats each had ligation of the terminal ileum (obstruction model) or of the terminal ileum and mesenteric artery (obstruction with ischemia model). Each rat received 3 ml of barium, meglumine sodium diatrizoate, iohexol, neat perfluorooctyl bromide, neat perfluorohexyl bromide, or saline (control animals). Contrast media were given at the recommended concentrations, and their progression was evaluated on serial radiographs by an observer who was not aware of the model or the contrast medium given. When one contrast material reached the point of obstruction, all rats in the group were sacrificed and a final radiograph was obtained. Three radiologists, who were not aware of the contrast medium given, on two separate occasions independently reviewed the radiographs and ranked the contrast agents for their relative radiopacity, mucosal definition, speed of transit, gastric retention, and bowel distension. RESULTS: When data from both models were combined, perfluorocarbons were judged on the final image to be the most radiodense, to provide the sharpest mucosal detail, to have the least gastric retention, and to have faster progression than barium. Whereas meglumine sodium diatrizoate and iohexol reached the point of obstruction more rapidly than the perfluorocarbons and barium, they had the greatest gastric retention, caused the most bowel distension, and were the least radiopaque. CONCLUSION: Our results show that the radiopaque perfluorocarbons are suitable as gastrointestinal contrast agents and have favorable radiographic characteristics in this animal model. When these results are combined with the low-toxicity profile of perflubron, clinical evaluation of this agent for the radiographic assessment of bowel obstruction is warranted.

Absorption↗

Medical malpractice involving radiologic colon examinations: a review of 38 recent cases.

OBJECTIVE: Our purposes were to determine the causes of malpractice claims against radiologists performing contrast examinations of the colon and to design strategies to reduce litigation and diminish patient morbidity. MATERIALS AND METHODS: Reports of malpractice claims were collected from legal journals and databases between 1985 and 1994. For this period, 38 plaintiffs raised 52 allegations of malpractice that involved radiologists performing barium or Hypaque (meglumine diatrizoate; Winthrop Pharmaceuticals, New York, NY) colon examinations. For the 38 cases, 18 plaintiffs for decedents alleged that failure to diagnose colorectal cancer by barium enema examination caused delay in treatment and the patient's death. Eighteen plaintiffs alleged that improper performance of barium (17 cases) or meglumine diatrizoate (one case) colon examinations caused perforation of the colon, resulting in significant morbidity (15 cases) or death (three cases). Miscellaneous causes for malpractice claims were recorded in two cases. RESULTS: In 18 cases of failure to diagnose colorectal cancer, the initial radiographs were interpreted as follows: normal findings in 14 cases, diverticulosis in one case, and spastic bowel in two cases; in the remaining case, colon cancer was missed because of nonopacification of the cecum. In retrospect, 17 of 18 colorectal cancers were visualized. The delay in the diagnosis of colorectal cancer ranged from 5 to 72 months. Missed colorectal cancers occurred in the cecum (two cases), transverse colon (two cases), rectosigmoid area (nine cases), or unspecified area (five cases). In 18 cases of colon perforation, the site was the cecum (one case), transverse colon (one case), extraperitoneal rectum (seven cases), rectosigmoid area (one case), colostomy stoma (two cases), or unspecified area (six cases). One patient experienced anaphylactic shock that required hospitalization. One underwent unnecessary surgery because barium enema films showing colon cancer were mislabeled with her name. CONCLUSION: On the basis of our analyses of malpractice claims, we suggest strategies to prevent medicolegal litigation. Strategies include communicating with the patient about the type and indications of the barium enema examination, performing digital rectal examinations on all patients to detect distal rectal lesions or strictures, recognizing colon perforation, and obtaining immediate surgical consultation if colon perforation occurs. The number of missed colon cancers may be reduced by reading twice or reviewing at a later time all barium enema examinations.

Adult↗

Beneficial effect of ETA receptor blockade in a rat model of radiocontrast-induced nephropathy.

Endothelin has been implicated in the pathogenesis of acute renal failure associated with radiocontrast media. The current study was designed to determine the effect of endothelin receptor blockade in a model of radiocontrast-induced nephropathy. Inhibition of prostanoids and nitric oxide with indomethacin and L-nitroarginine methyl ester (L-NAME) predisposes rats to the nephrotoxic effects of radiocontrast media and, therefore, has been proposed as a clinically relevant model. Separate groups of conscious rats were given the ETA receptor antagonist, A-127722 (3, 10, or 30 mg/kg), or water (1 mL/kg) by oral gavage. All rats were then given indomethacin (10 mg/kg), L-NAME (10 mg/kg), and the contrast agent, diatrizoate (6 mL/kg), by intravenous injection at 15-min intervals. Urine was collected for the subsequent 24 h by placing rats in metabolism cages. When indomethacin, L-NAME, and diatrizoate were administered without A-127722, rats displayed typical signs of renal failure; protein excretion was increased from a baseline of 13 +/- 2 to 33 +/- 8 mg/day (p < 0.05) and plasma creatinine increased from 0.52 +/- 0.01 to 0.62 +/- 0.04 mg/dL (p < 0.05). ETA receptor blockade prevented the rise in protein excretion and plasma creatinine in a dose-dependent manner. In separate series of clearance experiments, A-127722 completely inhibited the renal effects of exogenous ET-1. These results suggest that endothelin plays a role in the hemodynamic events in this model and that ETA receptor antagonists should be investigated as potential therapeutic agents for radiocontrast-induced nephropathy.

Acute Kidney Injury↗

Early glomerular effects of contrast media in rats: evaluation with a simple method.

The aim of this study was to evaluate the early effects of high and low-osmolar contrast media on glomerular function in rats by using a new method based on the measurement of the urinary excretion of 99mTc-DTPA. Thirty-six Sprague-Dawley male rats were examined: nine rats were injected with diatrizoate (ionic high-osmolar contrast medium), nine rats with iohexol (nonionic low-osmolar contrast medium), and nine rats with saline as controls. The urinary excretion of 99mTc-DTPA in the first minutes after i.v. injection was assumed as an index of glomerular filtration rate. A lower urinary excretion of 99mTc-DTPA was found in rats treated with contrast media in comparison with control rats. This effect was more evident after diatrizoate but was statistically significant also after iohexol. In conclusion, a reduction in the glomerular filtration rate probably occurs in the first few minutes after contrast media administration. The measurement of urinary excretion of 99mTc-DTPA could be a simple method to detect acute glomerular effects due to contrast media or to other drugs.

Animals↗

Addition of calcium or other cations and of oxygen to ionic and non-ionic contrast media. Effects on cardiac function during coronary arteriography.

Metrizamide is a new non-ionic water soluble contrast agent. Isolated rabbit hearts were perfused with solutions of 1) metrizamide, 2) metrizamide with plasma equivalent amounts of cations, 3) oxygenated metrizamide, 4) oxygenated metrizamide with cations, 5) diatrizoate. Solutions of 1) metrizamide, 2) metrizamide with plasmaequivalent amounts of cations, 3) metrizamide with calcium ions, 4) metrizoate (ionic medium) with calcium ions, metrizoate with 5) low and 6) high sodium content and 7) diatrizoate were injected into the left coronary artery of dog hearts in vivo. Maximal change of myocardial contractile force was measured with a strain gauge arch. Changes in aortic blood pressures were also recorded. In both sets of experiments metrizamede affected these parameters less than the ionic contrast media. The addition of calcium ions to both ionic and non-ionic media reduced the adverse effects on the observed cardiac funcitons, while simultaneous addition of plasma equivalent amounts of four cations as metrizoate salts had no beneficial effects. Sodium ions had in high concentration deleterious effects on cardiac performance. Oxygen saturation of the contrast medium had no observable effect. The adverse effects on cardiac mechanical function of sodium ions and possibly other cations contained in a contrast medium solution might be counterbalanced by the addition of calcium ions to the solution.

Aminoglycosides↗

[A new contrast medium (author's transl)].

Report about a new roentgen contrast medium which contains as salt-forming cations the physiologic alpha-amino acids L-lysine, L-ornithine instead of the body-foreign N-methyl-glucamine base and as anion diatrizoate acids. Favourable results concerning clinical and roentgenological aspects of the lysine salt of diatrizoate acid are derived: general and local tolerance in angiographic and urologic examinations are good, pulse rate remains stable, blood pressure fluctuations are minimal.

Angiography↗

Iodinated contrast medium-induced potassium release: the effect of mixing ratios.

PURPOSE: It has been demonstrated that iodinated contrast medium (CM) causes the release of potassium into the intravascular spaces, resulting in an increase of serum potassium. The purpose of the present study was to assess the effect of mixing ratio on potassium release rates by using various mixing ratios with human blood in vitro. MATERIALS AND METHODS: Fresh human blood from 52 patients was mixed in vitro with iodinated CM at ratios ranging from 10:2 (blood:CM) to 10:10. Potassium release rates were determined during 30 min of exposure to CM. The test solutions used consisted of 370 mgI/ml iopamidol, 320 mgI/ml meglumine/sodium ioxaglate, and 370 mgI/ml meglumine/sodium diatrizoate. RESULTS: Potassium release rates increased gradually from ratios of 10:2 to 10:10. These changes were statistically significant. Among the three CM, diatrizoate induced the greatest potassium release, followed by iopamidol and then ioxaglate. CONCLUSION: Increasing mixing ratios caused an increase in potassium release rates.

Adult↗

Potential interference of agents on radioiodide thyroid uptake in the euthyroid rat.

UNLABELLED: The objective of this research was to investigate the merits of controlled studies with euthyroid rats as a means of determining the influence of dose and time after administration of agents that may interfere with radioiodide uptake in the thyroid. METHODS: Potassium iodide (KI), propylthiouracil (PTU), diatrizoate meglumine, and iohexol were selected to represent interfering agents. Two dose levels per agent were investigated. Doses used were 1 and 2 mg/kg of body weight for KI, 3.5 and 7 mg/kg of body weight for PTU, 1 mL/kg (282 mg I/kg) and 2 mL/kg (564 mg I/kg) of body weight for diatrizoate meglumine, and 1 mL/kg (300 mg I/kg) and 2 mL/kg (600 mg I/kg) of body weight for iohexol. The 24-h radioiodide thyroid uptake was determined after (131)I was given at 1, 8, 15, and 22 d after administration of interfering agents. RESULTS: The percentage radioiodide uptake value for the thyroid decreased significantly compared with controls for all agents and both doses on day 1 but returned to control levels by day 22 for all agents and both doses The time to return to normal varied between agents and doses. CONCLUSION: We conclude that the interfering agent, the dose given, and the length of time after administration influence the potential for an agent to affect radioiodide uptake in the thyroid. Further studies with the rat, preferably hyperthyroid, would be beneficial in generating data to reduce confusing contradictory information on the length and severity of interference of agents in radioiodide thyroid studies.

Animals↗

Radiographic contrast media and release of neutrophil specific proteins in vitro and after intravenous injection.

The neutrophil granulocytes contain granules in which different proteins are present. When activated the neutrophils degranulate and thereby release some of these proteins to the surroundings. Some of these proteins are specific for this type of cell, e.g., lactoferrin and elastase. To investigate the influence of contrast media (CM) on this release, blood was incubated with diatrizoate, ioxaglate, iohexol, iodixanol, hyperosmolar saline, and hyperosmolar mannitol at different concentrations, and the amount of the neutrophil specific proteins lactoferrin and elastase were measured. Decreasing protein concentrations were observed for increased medium concentrations, suggesting that the degranulation process of the neutrophils was inhibited by the CM. The protein concentrations were lowest after incubation with the two ionic media diatrizoate and ioxaglate. Significantly decreased values of plasma lactoferrin were observed one min after i.v. injection of iohexol or ioxaglate in 82 patients undergoing urography. There was no significant difference between the two CM.

Contrast Media↗

Comparison of intravenous contrast agents for CT studies in children.

One hundred and eighty children undergoing CT examination were randomly allocated to receive meglumine diatrizoate, iohexol, or iopamidol as their i.v. contrast agent. Minor side effects were detected in 85% of children receiving meglumine diatrizoate, in 18% of those receiving iohexol, and in 36% of those receiving iopamidol. Because many of these minor side effects cause patient motion or delay scanning after contrast medium injection, they potentially degrade image quality. These findings are an indication for the use of low osmolarity contrast agents for i.v. use in pediatric CT imaging.

Child↗

Granulocyte chemotaxis before and after urography. Influence of four different radiographic contrast media.

Granulocytes isolated from whole blood of 10 volunteers with Hypaque/Ficoll or Percoll gradient centrifugation showed a significant inhibition of their chemotactic response when incubated with diatrizoate. The influence of 4 different i.v. injected radiographic contrast media (CM) on granulocyte chemotaxis was evaluated using the under agarose assay. Each CM was injected in 10 consecutive outpatients referred for urography. Cells and serum were obtained before and 20 min after the injection of CM. Autologous serum was used as chemoattractive agent, and the cell suspensions from both samples were tested against serum drawn both before and after the injection of CM. No significant changes in granulocyte chemotaxis or the chemotactic potential of serum were seen. Furthermore, there was no change in the chemotactic response towards homologous serum or N-fmlp after injection of diatrizoate or iohexol. In conclusion, the investigation did not unveil any change in granulocyte chemotaxis 20 min after the injection of CM in the 40 subjects studied.

Cell Separation↗

[The evaluation of renal tolerance for roentgen contrast media by determination of urinary kidney-specific proteins].

In the present trial kidney-specific proteins were studied enzymatically or quantitatively in patients' urine after intravascular administration of water-soluble X-ray contrast media, in order to judge about their renal tolerance. 5 clinical trials (phase III), including 198 patients, were carried through, within several radiological examinations. The examined X-ray substance was Iosimide, a new monomeric, nonionic low osmolar c.m. It was compared to the nonionic Iopromide and Iopamidol as well as to the ionic, high osmolar sodium-meglumine-diatrizoate. Enzyme activities of alanine-aminopeptidase (AAP), gamma-glutamyltransferase (GGT), beta-n-acetylglucosaminidase (NAG), kallikrein with creatinine as point of reference were kinetically measured in 4 urine samples (1 before c.m. administration the others as 24 hours urine samples of the following 3 days). Beside the quantitative determination of protein and albumin an electrophoresis was started, when diagnosis was obvious. Kallikrein was brought to the diagnostic palette of this study in order to include the distal segment of the nephron. The specific protein excretion patterns of nonionic c.m. in urine are not different from each other. In contradiction to this, the results of the low osmolar nonionic Iosimide compared to the high osmolar diatrizoate, show evident differences for the benefit of Iosimide.

Acetylglucosaminidase↗

Effects of contrast media on the RR and QT interval during coronary arteriography.

During coronary arteriography, transient prolongation of the RR and QT intervals can be observed to occur. Animal experiments have suggested that low-osmolality contrast media have less effect, but there have been few clinical studies of this phenomenon. We analyzed 95 electrocardiographic records from patients who had undergone coronary arteriography and assessed the maximal prolongation of the RR and QT intervals. The contrast media used for arteriography included meglumine sodium diatrizoate, iopamidol, iohexol, and meglumine sodium ioxaglate. Diatrizoate caused the greatest electrocardiographic changes. Among the low osmolality contrast media, ioxaglate caused the smallest bradycardial effect and iohexol the smallest prolongation of the QT interval. It appears necessary to consider some additional factors for osmolality or ionicity, such as the chemotoxicity of the chemical structure of the iodinated contrast medium moiety, when assessing their potential adverse effect on the cardiac conduction system.

Contrast Media↗

Effects of contrast media on myocardial function during acute left ventricular failure in the dog.

We studied the hemodynamic side effects of intracoronary injection of contrast media during acute ischemic heart failure by using anesthetized dogs. Induction of failure was performed by microembolization of the area supplied by the left main coronary artery. Six ml of iohexol (Omnipaque) increased contractility during the normal state, while this contrast medium induced no alterations in any of the recorded hemodynamic variables during left ventricular failure. Ioxaglate (Hexabrix) was also well tolerated during the normal state, while sodium-meglumine diatrizoate (Renografin) markedly decreased systolic variables. However, in the failing heart both ioxaglate and diatrizoate resulted in greater reduction in all systolic variables than in the normal heart. We conclude that both ionic contrast media may be harmful in acute ischemic heart failure. Non-ionic iohexol appears safer in this condition.

Animals↗