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PubMed1991

Extravascular toxicity of two magnetic resonance contrast agents. Preliminary experience in the rat.

We compared the relative toxicities of standard concentrations of two magnetic resonance imaging (MRI) contrast agents, ionic gadolinium diethylenetriaminepentacetic acid (DTPA) and low-osmolar gadolinium-1, 4, 7 tris (carboxymethyl)-10-(2'-hydroxypropyl)-1, 4, 7, 10 tetra-azacyclododecane (HP-DO3A) with that of the conventional radiographic contrast medium meglumine diatrizoate, when extravasated into the deep dermal tissues of laboratory rats. Gadolinium-DTPA caused moderate necrosis, hemorrhage, and edema which was not statistically different than meglumine diatrizoate. In contrast, gadolinium HP-DO3A was significantly less toxic than meglumine diatrizoate. Additional experience will be needed in order to determine whether these laboratory results will be clinically relevant in humans.

Animals↗

PubMed1993

Effects of vasoconstrictors on rabbit coronary arteries exposed to isotonic ionic and nonionic contrast media.

RATIONALE AND OBJECTIVES: Vasodilation is a well-known side effect of contrast media (CM) that is primarily explained by the hyperosmolality of the media. Few reports have dealt with the influences of chemotoxicity and ion toxicity on vessel tone. We compared the effects of solutions iso-osmolar to plasma of iohexol (nonionic monomer), ioxaglate (ionic dimer), diatrizoate (ionic monomer), and mannitol on responses to vasoconstrictors (potassium chloride [KCl], histamine, and endothelin-1). The aim of this study was to investigate if differences in chemotoxicity and ion toxicity could contribute to the changes in vessel tone seen clinically during arteriography. METHODS: Segments of rabbit coronary arteries were mounted between two L-shaped prongs in tissue baths with buffer solution or CM solutions. Their responses to increasing concentrations of a vasoconstrictor were measured. The maximal contraction of the vasoconstrictor (Emax) and the concentration of the vasoconstrictor causing half maximal contraction (EC50) were calculated. RESULTS: Iohexol caused the same changes as the nonionic solution of mannitol. The media reduced the actions of KCl, histamine, and endothelin-1 to 50% to 60% of their action in buffer. The ionic CM, ioxaglate and diatrizoate, caused a more pronounced inhibition of histamine and almost totally inhibited the action of KCl. The action of endothelin-1 was inhibited to a greater extent by iohexol and mannitol than by ioxaglate and diatrizoate. CONCLUSIONS: Different types of iso-osmolar CM interact differently with vasoconstrictors. These effects are caused by differences in chemo- and ion toxicity. These interactions might contribute to the differences in vasodilatation found clinically.

Animals↗

PubMed1994

Renal tolerance of gadolinium-DOTA and gadolinium-DTPA in rats.

RATIONALE AND OBJECTIVES: Although gadolinium chelates are mainly eliminated by the kidney, there is limited information about their effects. The renal tolerance of these compounds on renal function in an in vivo rat model are evaluated. METHODS: A combination of renal ischemia and intrarenal iodinated contrast agent infusion (diatrizoate) led to a reproducible and reversible model of acute renal failure (n = 5). Using this model, the renal tolerance of gadolinium DOTA (Gd-DOTA) (n = 10) and gadolinium DTPA (Gd-DTPA) (n = 10) were evaluated. The effects of the association of Gd-DOTA with diatrizoate (n = 5) on renal function also were assessed. RESULTS: Gadolinium DOTA induced no change in serum creatinine and creatinine clearance. Gadolinium DTPA induced a significant increase in serum creatinine (50 to 83 +/- 5 and 70 +/- 6 mumol/L) before and at 24 and 48 hours, respectively (P < .05), and a decrease in creatinine clearance from 1.6 +/- 0.1 to 0.8 +/- 0.1; 1.2 +/- 0.1 mL/mL before and at 24 and 48 hours, respectively (P < .05). In this model, Gd-DOTA did not modify the renal tolerance of diatrizoate as assessed with serum creatinine and creatinine clearance. CONCLUSIONS: Gadolinium DOTA is not nephrotoxic and can be infused in association with iodinated contrast media. In this model, Gd-DTPA induced reversible renal failure.

Acute Kidney Injury↗

PubMed1997

Comparison of iodinated contrast media-induced renal vasoconstriction in human, rabbit, dog, and pig arteries.

RATIONALE AND OBJECTIVES: Contrast media (CM)-induced renal vasoconstriction is an important factor in the pathogenesis of CM-induced nephrotoxicity. The effects of ionic, high-osmolar CM sodium/meglumine diatrizoate and nonionic, low-osmolar CM iohexol and iopamidol were studied in rabbit, dog, and pig renal arteries and compared with human tissue in an organ bath. METHODS: Isometric contractions were induced by increasing concentrations of CM and high-osmolar glucose solution. RESULTS: Contrast media and glucose elicited contractions in human renal arteries of 32% (diatrizoate), 20% (iohexol), 30% (iopamidol), and 22% (glucose). Rabbit and dog renal arteries demonstrated contractions of 30% and 46% (diatrizoate), 15% and 23% (iohexol), 15% and 26% (iopamidol), and 11% and 40% (glucose), respectively, of the control. There was a vasorelaxing effect of all CM tested on pig renal artery. CONCLUSIONS: Responses in rabbit and dog renal arteries were similar to those in human renal arteries and could serve as models for investigating CM-induced renal vasoconstriction.

Animals↗

PubMed1997

Comparative cytotoxicity of low- and high-osmolar contrast media to human fibroblasts and rat mesangial cells in culture.

RATIONALE AND OBJECTIVES: The authors investigate the relative sensitivity of rat mesangial cells to iodinated contrast media (CM) and control solutions versus less differentiated cells (ie, human fibroblasts) and compare the effects of low-osmolar ionic (ioxaglate) and nonionic (iopamidol) and high-osmolar ionic (diatrizoate) CM on rat mesangial cells. METHODS: The cytotoxic effects of ioxaglate and control solutions of sodium chloride and mannitol were assessed by neutral red uptake in isolated rat mesangial cells and human fibroblasts. In a second series of studies, the cytotoxic effects of ioxaglate, iopamidol, and diatrizoate (0 to 100 mg I/mL) on rat mesangial cells were compared. RESULTS: Rat mesangial cells were more sensitive to the cytotoxic effects of ioxaglate than the less differentiated human fibroblasts between 70 and 100 mg I/mL. A similar discrepancy was observed in the case of control solutions, sodium chloride, and mannitol. Ioxaglate and iopamidol induced a similar level of cytotoxicity in rat mesangial cells whereas the high-osmolar agent diatrizoate was significantly more cytotoxic. However, the calculated inhibitory concentrations of 50% of all three CM were associated with similar osmolalities, suggesting a major role for this parameter in the case of such media. CONCLUSIONS: Rat mesangial cells are more sensitive to the cytotoxic effects of CM and hyperosmolar solutions than the less differentiated human fibroblasts. High-osmolar CM are more cytotoxic than ionic and nonionic low-osmolar CM to rat mesangial cells. Ionicity seems to play no deleterious role at similar iodine concentrations because ioxaglate and iopamidol had equivalent cytotoxic effects on mesangial cells.

Animals↗

PubMed2002

Radiocontrast-induced renal tubular cell apoptosis: hypertonic versus oxidative stress.

RATIONALE AND OBJECTIVES: Radiocontrast-induced nephropathy (RCIN) is a major complication of intravascular radiocontrast administration. Renal tubular cell apoptosis is a feature of RCIN, which is related to hypertonicity of contrast agents. Because a hyperosmolal extracellular environment induces oxidative stress via reactive oxygen species, we tested the hypothesis that antioxidants decrease hypertonicity-induced apoptosis of renal epithelial cells. We analyzed the effects of the antioxidants N-acetylcysteine (NAC) and taurine on hypertonicity-induced apoptosis of renal epithelial cells in vitro. METHODS: Madin Darby Canine Kidney (MDCK) cells were incubated with the highly hyperosmolal, ionic radiocontrast agent diatrizoate (20% vol/vol, 6 hours) or with equally hyperosmolal (640 mOsm/kg) NaCl solutions. DNA fragmentation, which is a hallmark feature of apoptosis, was assessed quantitatively using flow cytometry after propidium iodide staining and qualitatively using agarose gel electrophoresis. RESULTS: Both diatrizoate and NaCl induced DNA fragmentation in MDCK cells. Taurine (10 mmol/L) reduced DNA degradation in both diatrizoate- [79.5 +/- 2.3% versus 72.2 +/- 3.0%; P = 0.0088] and NaCl- [49.5 +/- 4.0% versus 39.4 +/- 1.0%; P = 0.0271] treated cells. In contrast, NAC (10 mmol/L) failed to reduce the DNA breakdown in this model of hypertonicity-induced renal tubular cell apoptosis. CONCLUSIONS: The radiocontrast/hypertonicity-induced DNA fragmentation of MDCK cells is attenuated by taurine but not by NAC. Because both agents are antioxidants, the antioxidant property is not sufficient for the observed cytoprotective effect. Hence, the antiapoptotic effect of taurine has to be attributed to other, yet to be defined mechanisms. Our results suggest that pharmacological doses of taurine may be particularly protective against RCIN.

Acetylcysteine↗

PubMed1977

Renal ischemia and contrast urography.

Exposure to urographic contrast material, meglumine diatrizoate, in a previously ischemic kidney was investigated for its effect on renal function. Eleven mongrel dogs, 19.8-32.7 kg in weight, having the left kidney ischemic for 90 minutes were given either 4 cc/kg meglumine diatrizoate or control, Ringer's lactate solution. The effect on creatinine clearance of the left kidney was determined acutely and at 72 hours. Statistical analysis of the data reveals no deleterious effect from exposure to meglumine diatrizoate over and above the effect of the ischemic episode. There was no statistically significant effect on recovery of renal function in this animal model.

Animals↗

PubMed2003

Effects of contrast media on erythrocyte aggregation during sedimentation.

To evaluate the effects of contrast media (CMs) on erythrocyte aggregation, we measured the erythrocyte sedimentation with Westergren method at 25 degrees C. CMs were diatrizoate (Urografin 76%) for ionic CM and iopamidol (Iopamiron 370) for nonionic CM. Swine red blood cells (RBCs) were suspended in autologous plasma containing diatrizoate (URO), iopamidol (IOP), and saline (SAL) at 6.7% w/w, as well as in plasma alone (PLA), at 40% of the hematocrit. Sigmoid sedimentation curves were fitted to the Puccini et al. (1977) equation, and the average number of RBCs per aggregate m was calculated by Stokes' law against the time t. According to the Murata-Secomb (1988) theory we estimated the collision rate K between two aggregates from dm/dt in the stationary phase during sedimentation. Corresponding to the maximal ESR, the dm/dt (in cells/s) was 0.52 in PLA, 0.09 in SAL, 0.06 in URO and 0.03 in IOP, so that K also decreased in proportion to dm/dt from 145 fL/s in PLA to 8 fL/s in IOP. Both the ionic and nonionic CMs tend to inhibit the RBC aggregation more than that in SAL; the latter iopamidol appears to be inhibitory more than the former diatrizoate in autologous plasma.

Animals↗

PubMed1976

Extravascular contrast material: the major component of contrast enhancement.

The distribution volume of 125l-diatrizoate in rat tissues was studied 5 seconds to 5 minutes after intravenous injection and 5 seconds to 2 minutes after intra-arterial injection. Immediately after injection, diatrizoate was distributed into a larger volume than plasma. Marked temporal changes in the distribution volume of individual tissues occurred during the first 2 minutes. At 5 minutes, the diatrizoate space approached the total extracellular fluid volume, with more than 80% of the contrast agent remaining outside the blood vessels. Thus the relative magnitude of contrast enhancement of a tissue appears to be related to the volume of the rapidly equilibrating extracellular space. Intra-arterial administration can significantly overload muscle with contrast material for about 2 minutes. This and other temporal changes in contrast distribution may prove useful in contrast-enhanced computed tomography using short scanning times.

Adipose Tissue↗

PubMed1978

Cytogenetic effects of contrast media and triiodobenzoic acid derivatives in human lymphocytes.

Micronuclei counts in blood samples from 9 patients before and after angiocardiography have confirmed previous results suggesting the diatrizoate contrast medium was largely responsible for the observed cytogenetic damage. To discover the agents in the medium causing the cytogenetic damage, we exposed human lymphocyte cultures to diatrizoate and to the monoamino- and diamino-derivatives of triiodobenzoic acid. The results show the amino-derivatives are capable of inhibiting mitosis and inducing micronuclei and chromosome aberrations at lower concentrations than diatrizoate.

Adolescent↗

PubMed1988

Effect of chymopapain on the meninges studied in an experimental model.

The effect of chymopapain and contrast media in the epidural space on meninges has not been studied conclusively. The authors injected chymopapain into the epidural space of monkeys and measured the degree of arachnoid fibrosis that resulted. Animals were given injections of 1.2 mL of diatrizoate (280 mg iodine per milliliter), chymopapain (100 IU/mL), kaolin (100 mg/mL) (as a positive control), or saline (0.9%) (as a negative control). Three months later the animals were killed; the dural sac was removed intact and was fixed, sectioned, stained, and examined with light microscopy. Kaolin-treated animals developed mild to marked fibrosis of the dura. The saline- and diatrizoate-treated animals developed little or no evidence of fibrosis. One of four chymopapain-treated animals developed degenerative changes in dorsal nerve roots and fibrosis in the adjacent arachnoid. The other chymopapain-treated animals had little or no evidence of fibrosis. The studies suggest that neither diatrizoate nor chymopapain causes arachnoid fibrosis.

Animals↗

PubMed1992

Ionized calcium levels in coronary sinus blood during coronary angiography: effects of four contrast media.

The changes in ionized calcium level in the coronary sinus during coronary angiography were compared for four contrast media (meglumine sodium diatrizoate, iohexol, iopamidol, and meglumine sodium ioxaglate) in 44 subjects. Blood samples were collected before and 5, 15, and 30 seconds after injection of contrast medium into the left coronary artery. The hematocrit and ionized calcium level of each specimen were measured. Meglumine sodium diatrizoate produced the largest changes in hematocrit and ionized calcium level. The time-concentration curve of the hematocrit was similar for all four contrast media, but diatrizoate and ioxaglate produced a prolonged decrease of ionized calcium. The cause of this is not clear, but the phenomenon may be related to differences of ionic status among the contrast media. With respect to maintenance of the ionized calcium level, nonionic low-osmolality contrast medium with added calcium may be preferable for coronary angiography.

Adult↗

PubMed1996

Do iodinated contrast media increase serum potassium levels?

PURPOSE: To test the hypothesis that iodinated contrast media may induce an elevation in serum potassium level. MATERIALS AND METHODS: Protocol A: After intravenous infusion of contrast media into six rabbits, alterations of potassium ion concentrations were measured. Protocol B: Fresh rabbit blood was mixed in vitro with contrast media, and the fluctuations in potassium were monitored over a 30-minute period. Protocol C: Similar to protocol B, except that blood from humans with no reaction to contrast media was used. RESULTS: For protocol A, blood potassium levels increased above baseline levels. The elevations were statistically significant (P < .05). For protocol B, diatrizoate and ioxaglate caused a gradual increase in blood potassium levels, but iopamidol did not. In protocol C, all three contrast media caused statistically significant elevation in potassium levels. The release of potassium was statistically significant at 5 minutes (P < .05 for diatrizoate and ioxaglate, and P < .01 for iopamidol). The mean release rates (+/- standard deviation) by means of linear regression analysis were 0.0190 mmol/min +/- 0.0112 with diatrizoate, 0.0159 mmol/min +/- 0.0057 with iopamidol, and 0.0088 mmol/min +/- 0.0033 with ioxaglate. CONCLUSION: Iodinated contrast media increase blood potassium levels causing release of potassium into intravascular spaces. This potassium release may play some role in contrast medium-induced adverse reactions.

Animals↗

PubMed1987

Tubular nephrotoxicity after intravenous urography with ionic high-osmolal and nonionic low-osmolal contrast media in patients with chronic renal insufficiency.

Nephrotoxicity of intravenous contrast media is more frequent and striking in patients with risk factors, the major one being preexisting chronic renal insufficiency. New nonionic low-osmolal contrast media allegedly have less nephrotoxicity than the traditional ionic high-osmolal ones. This was tested for two contrast media in a group of 18 patients with stable chronic renal insufficiency. The urinary excretion of two brush-border enzymes (alanine aminopeptidase, AAP, and gamma-glutamyl transpeptidase, gamma-GT) and of a lysosomal enzyme (N-acetyl-beta glucosaminidase, NAG), functional markers of tubular injury, were measured before and after intravenous urography with an ionic high-osmolal radiocontrast medium, meglumine sodium diatrizoate, or with a non ionic low-osmolal one, iopamidol. Urinary NAG excretion did not change significantly after administration of either contrast media. Urinary AAP and gamma-GT excretion increased significantly (p less than 0.01) after diatrizoate. After iopamidol, only gamma-GT excretion increased significantly (p less than 0.05). Our data suggest that the nonionic low-osmolal radiocontrast medium iopamidol is less toxic to tubules than the ionic high-osmolal medium diatrizoate and that the brush-border enzymes AAP and gamma-GT are sensitive markers for this toxicity.

Acetylglucosaminidase↗

PubMed1990

Uninephrectomy does not potentiate contrast media nephrotoxicity in the streptozotocin-induced diabetic rat.

We studied the effect of radiographic contrast media on renal function in both streptozotocin-induced diabetic rats and normoglycemic rats with reduced renal functional mass. Male Sprague-Dawley induced-diabetic rats and weight-matched controls were divided into unilaterally nephrectomized and intact groups prior to an intravenous challenge with sodium diatrizoate (Urografin) at two dose levels, 1,300 and 2,600 mg iodine/kg. Serum creatinine concentration did not change on the 1st and 3rd day after a dose of 1,300 mg/kg of iodine in normal or induced-diabetic rats. Consequent to a dose of 2,600 mg/kg of iodine, induced-diabetic rats had a significant increase in serum creatinine levels to 0.9 +/- 0.45 mg/dl (control 0.68 +/- 0.11 mg/dl). The observed increase in serum creatinine concentration after treatment with sodium diatrizoate was significantly correlated with the degree of hyperglycemia, but not with prior unilateral nephrectomy. Unilateral nephrectomy, prior to administration of sodium diatrizoate did not potentiate the risk of radiocontrast agent injury in induced-diabetic rats. From these findings, we infer that: (1) streptozotocin-induced diabetes in the rat confers a risk for the development of radiocontrast-induced acute renal failure and (2) as judged by the rise in serum creatinine concentration after exposure, there is an increased risk of acute renal failure associated with a higher dose of radiocontrast material.

Acute Kidney Injury↗

PubMedDate not supplied

Blocking effect of radio-contrast media on cochlear depression.

Furosemide injection was used in a total of 72 guinea pigs to induce a cochlear dysfunction similar to the sensorineural loss associated with sudden deafness. Prior to the furosemide administration, 38 of the animals were treated with an injection of one of four radio-contrast media; methylglucamine and sodium diatrizoate, sodium iothalamate, methylglucamine and sodium iodamide, and methylglucamine diatrizoate. In the control animals, receiving only furosemide, both endocochlear potential (EP) and cochlear microphonic (CM) underwent a severe depression followed by recovery and subsequent secondary depression. Animals pretreated with one of the first three compounds showed little or no EP or CM depression. Animals pretreated with the fourth, methylglucamine diatrizoate, showed the same EP depression as the control animals. The possible mechanism for this blocking effect and its significance in the clinical treatment of sudden deafness is discussed.

Animals↗

PubMed1979

Ioxaglate, a new low osmolar contrast medium used in femoral angiography.

Ioxaglate, a new monoacid, dimeric contrast medium was compared with diatrizoate (Urografin 60%) in a series of 61 femoral angiographies. In a double blind group of 34 examinations all patients preferred ioxaglate which caused slight pain in only five cases, whereas after diatrizoate 14 patients felt severe pain (six were unable to keep their legs still) and 12 felt slight pain. Increase in heart rate and decrease in systolic and diastolic arterial blood pressure was seen after both contrast medium injections, but significantly less after ioxaglate than after diatrizoate.

Adult↗

PubMed1994

Cost-effective use of low-osmolality contrast media for CT of the liver: evaluation of liver enhancement provided by various doses of iohexol.

OBJECTIVE: Because of pending efforts to reform health care in the United States, judicious use of low-osmolality contrast media is important. We studied the effects of using various concentrations and volumes of iohexol, compared with the conventional dose and concentration of diatrizoate meglumine used for CT, to determine if a more cost-effective dose results in diagnostically efficacious liver enhancement. SUBJECTS AND METHODS: A total of 902 patients received one of nine different doses of IV contrast media. Eight doses of iohexol were used: 125 ml of iohexol 350 (350 mg l/ml, 44 g l/dose), 100 ml of iohexol 350 (35 g l/dose), 150 ml of iohexol 300 (300 mg l/ml, 45 g l/dose), 120 ml of iohexol 300 (36 g l/dose), 100 ml of iohexol 300 (30 g l/dose), 175 ml of iohexol 240 (240 mg l/ml, 42 g l/dose), 150 ml of iohexol 240 (36 g l/dose), and 125 ml of iohexol 240 (30 g l/dose). A single dose (150 ml) of diatrizoate meglumine 60% (w/v) was used (42 g l/dose). Contrast material was injected at a rate of 2 ml/sec. Scanning began 35-45 sec after injection. Quantitative analysis of enhancement was performed by obtaining region-of-interest measurements through the liver on scans obtained before and after injection of contrast material. Mean and maximum changes in hepatic density and mean time to maximum enhancement were measured. Mean time-density curves were subsequently derived for each dose of contrast material. Qualitative analysis of enhancement was performed by using subjective, previously defined criteria. All studies were interpreted in a double-blind fashion. RESULTS: Mean hepatic enhancement was greater with 125 ml of iohexol 350 and 150 ml of iohexol 300 than with other doses of contrast material (p < .05). Both 125 ml of iohexol 350 and 150 ml of iohexol 300 produced actual hepatic enhancement of more than 50 H for over 60 sec. The greatest maximum increase in hepatic density occurred with 125 ml of iohexol 350. When analyzed qualitatively, 150 ml of iohexol 300 resulted in the highest percentage of optimum enhancement. CONCLUSION: According to quantitative analysis, 125 ml of iohexol 350 administered at a rate of 2 ml/sec produces the best enhancement, whereas according to qualitative analysis, 150 ml of iohexol 300 produces the best enhancement. All doses of iohexol 240 provide poor enhancement compared with a conventional dose of contrast material of 150 ml of diatrizoate meglumine 60% or 150 ml of iohexol 300. A moderate cost savings can be achieved by using 125 ml of iohexol 350 for dynamic sequential CT.

Cost-Benefit Analysis↗