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PubMed1975

The renal vascular effects of meglumine diatrizoate.

Left ventricular injection of meglumine diatrizoate caused an initial (1-10 minute) decrease in renal vascular resistance followed by a late (30-minute) increase in renal vascular resistance. The late renal vasoconstrictor response was not blocked by bilateral cervical vagotomy, by renal adrenergic blockade or by renal alpha adrenergic receptor blockade; it was blocked by prior extracellular fluid volume expansion and blockade of the response of the kidney to angiotensin II. There was no effect on intrarenal distribution of blood flow. In the kidney perfused at constant flow, injections of meglumine diatrizoate into the kidney resulted in early renal vasodilation (1-5 minutes) with a return to control renal vascular resistance by 7 minutes; no vasoconstriction was observed. The renal vasodilatation was not abolished by prior treatment with atropine. Vasodilator responses identical to those observed with meglumine diatrizoate were obtained with 4.5% NaCl (equiosmolar to meglumine diatrizoate); no response was obtained with 0.9% NaCl. When given into either the left ventricle or the renal artery, meglumine diatrizoate caused an early reversible depression in renal extraction of para-aminohippurate; both 0.9 and 4.5% NaCl were without effect. The renal vasodilation produced by meglumine diatrizoate initially appears to be caused by its hyperosmotic properties; the late renal vasoconstrictor response appears to be mediated via an activation of the renin-angiotensin system. The depressive effect of meglumine diatrizoate on the renal extraction of para-aminohippurate is not related to its osmotic properties but rather to an effect of the organic iodinated molecule on cellular transport of para-aminohippurate.

Aminohippuric Acids↗
PubMed1980

[Reduced cardiotoxicity of contrast media in angiocardiography. Comparative clinical study using diatrizoate with added calcium or metrizamide (author's transl)].

Cardiodepressive side effects of angiocardiography can be reduced by using non-ionic metrizamide (Amipaque) or adding calcium to diatrizoate (Urografin 76%). In 15 patients with coronary artery disease undergoing heart catheterization, we compared cardiac side effects of coronary angiography and left ventricular angiography using metrizamide and diatrizoate with and without additional calcium (11.3 mmol/l) as contrast media under randomized conditions. In selective intracoronary injection with diatrizoate alone, peak left ventricular pressure and contractility (dP/dtmax) showed a fall of 30 +/- 11% and 31 +/- 15% (n = 33 injections). Using diatrizoate with added calcium (11.3 mmol/l), the fall was only 23 +/- 12% and 20 +/- 10% respectively (n = 31 injections). With metrizamide (n = 32 injections) cardiac side effects are even less and the decrease in pressure and contractility only 13 +/- 10% and 7 +/- 7% respectively, which its highly significant (p less than 0.0001) compared with the effect of diatrizoate. The heartrate slowing, not essentially altered by calcium addition, was minimal using non-ionic metrizamide. In left ventricular angiography, the pressure fall in the late phase after injection of diatrizoate, caused by decrease peripheral vascular resistance (vasodilation), was lacking when injecting metrizamide (p less than 0.001). Metrizamide has even less cardiodepressive side effects than diatrizoate with additional calcium when used in angiocardiography and seems to be suitable particularly for the evaluation of high risk patients.

Adult↗
PubMed2003

Absorption of L-lysine diatrizoate from the gastrointestinal tract: the effect of surgery, inflammation, and neoplasia.

BACKGROUND AND AIMS: To ascertain whether the absorption of L-lysine diatrizoate, a sodium-free salt of the contrast-giving diatrizoic acid from the gastrointestinal tract is increased by surgery, inflammation, and neoplasia. PATIENTS AND METHODS: The prospective study comprised 32 patients who were undergoing radiological examination of the upper gastrointestinal tract with a contrast medium containing L-lysine diatrizoate and 52 further patients who were undergoing examination of the lower gastrointestinal tract in the same way. The concentration of diatrizoic acid was determined by high-pressure liquid chromatography in blood samples taken before and immediately after the radiological examinations. The results were examined in terms of sex, age, surgical history, and any evidence of inflammatory or neoplastic diseases. RESULTS: The serum diatrizoic acid concentration in patients tested after oral administration was 3.62 microg/ml. In patients who had undergone operation the titer was lower than in those who had not been operated on. Serum diatrizoic acid concentration in patients tested after rectal administration was 0.30 microg/ml. In patients suffering from inflammatory conditions or neoplasms the titer was significantly higher than in the other patients. CONCLUSION: The L-lysine salt of diatrizoic acid is absorbed in larger amounts from the upper gastrointestinal tract than from the lower. Absorption is not increased after surgical operations on the viscera. However, inflammatory conditions and neoplasms involving the large bowel increase the uptake of the contrast medium from the intestine.

Abdomen↗
PubMed2003

[Absorption of L-lysine diatrizoate from the gastrointestinal tract: the influence of surgery, inflammation and neoplasia].

PURPOSE: To ascertain whether the absorption of L-lysine diatrizoate, a sodium-free salt of the contrast-giving diatrizoic acid, from the gastrointestinal tract is increased by surgery, inflammation or neoplasia. MATERIAL AND METHODS: Using contrast medium containing L-lysine diatrizoate for intestinal opacification, this prospective study compared 32 radiographic examinations of the upper gastrointestinal tract with 52 radiographic examination of the lower gastrointestinal tract. In blood samples taken from the patients immediately after the radiographic examinations, the concentration of diatrizoic acid was determined by high pressure liquid chromatography. The results were correlated with sex, age, surgical history and any evidence of inflammatory or neoplastic diseases. RESULTS: The serum diatrizoic acid concentration in patients after oral administration was 3.62 (95% CI, 2.86 - 10.17) microg/ml. The titer was lower in patients who had undergone abdominal surgery than in patients without surgery. Serum diatrizoic acid concentration in patients after rectal administration was 0.30 (95% CI, 0.13 - 0.60) microg/ml. The titer was significantly higher (p < 0.05) in patients suffering from inflammatory conditions or neoplasms than in the other patients. CONCLUSION: The L-lysine salt of diatrizoic acid is absorbed in larger amounts from the upper than from the lower gastrointestinal tract. Absorption is not increased after abdominal surgery. However, inflammatory conditions and neoplasms of the large bowel increase the uptake of contrast medium from the intestine.

Abdomen↗
PubMed1988

Diatrizoate levels in cerebrospinal fluid following intravenous administration. Role of fluid production rate.

The central nervous system (CNS) may be highly susceptible to the toxic effects of conventional contrast media (CM). The current study quantifies levels of diatrizoate in canine cerebrospinal fluid (CSF) following intravenous administration and examines how these levels change as CSF production rate is reduced. Cerebrospinal fluid was collected continuously from the cisterna magna of anesthetized dogs before and after the administration of diatrizoate (1 mL/kg bolus followed by a 12.5 microliters/kg/minute maintenance infusion, IV). The influence of CSF production rate on CSF diatrizoate levels was examined by injecting acetazolamide (30 mg/kg, IV). Diatrizoate levels in CSF were quantified by a high performance liquid chromatography (HPLC) method. Baseline CSF production was 81.5 microliters/minute and dropped to 37.4 microliters/minute following diatrizoate and to 29.5 microliters/minute following acetazolamide. The concentration of diatrizoate in CSF averaged 166 micrograms/mL and increased significantly to 379 micrograms/mL following acetazolamide with no change in serum concentration (1.3 mg/mL). These experimental results suggest that appreciable quantities of intravenously administered diatrizoate may enter the CNS, and that these quantities may increase significantly with reduced CSF production. This may help to explain CSF enhancement and certain CNS toxicity after the intravenous administration of CM.

Animals↗
PubMed1992

Effect of diatrizoate on the function of the isolated perfused rat kidney.

The mechanism of the nephrotoxicity of water-soluble contrast media (WSCM) remains ill defined. We have studied the effect of diatrizoate on the isolated perfused rat kidney (IPRK). Emphasis was on the effect of low- and high-dose diatrizoate on glomerular filtration rate (GFR), renal perfusate flow (RPF), fractional excretion of albumin (FE Alb) and fractional reabsorption of sodium (FR Na). The addition of diatrizoate to the IPRK led to a dose-dependent biphasic change in RPF and GFR characterized by an initial transient increase followed by a marked and sustained decrease. Diatrizoate induced a diuresis and a parallel increase in urinary sodium excretion (fall of FR Na). Fe Alb was also increased in kidneys exposed to diatrizoate. Electron microscopy of a control kidney showed preservation of cellular architecture, which contrasted with the observed cytoplasmic vacuolation of proximal tubular cells after perfusion with diatrizoate. This study confirms a direct effect of WSCM on the function of the IPRK. In this experimental model, diatrizoate reproduces the effects observed in vivo on GFR and renal perfusion.

Animals↗
PubMed1990

Gentamicin nephropathy and contrast media. A comparison between diatrizoate and iohexol in rats.

Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol or saline in 30 rats, where a tubulo-interstitial nephropathy was induced by gentamicin given over a 14-day period. Another 10 rats who had an injection of saline served as controls. Iohexol increased the excretion of lactate dehydrogenase significantly more than both saline and diatrizoate for the first 3 days, whereas diatrizoate had no effect. Both media caused significantly increased excretion of L-gamma-glutamyltransferase compared with saline, but iohexol significantly more than diatrizoate. Compared with saline S-creatinine was significantly increased following iohexol at 24 h, 3 and 9 days, and following diatrizoate only at 9 days. Among rats having gentamicin light microscopy revealed more severe changes in kidneys exposed to iohexol than to either diatrizoate or saline 3 days after their injection. Six days later no obvious differences were found between the 3 groups. In conclusion, iohexol induced more renal dysfunction than diatrizoate in this animal model of gentamicin induced nephropathy.

Acetylglucosaminidase↗
PubMedDate not supplied

Nephropathy induced by intramuscularly administered glycerol and contrast media in rats. A comparison between diatrizoate, iohexol and ioxilan.

Urine profiles (albumin, glucose, NAG, LDH, GGT, sodium, and phosphate) were followed for 14 days after intravenous injection of either diatrizoate, iohexol, ioxilan, or saline in 24 Wistar rats with a glomerular and tubular dysfunction induced by intramuscularly (i.m.) administered glycerol. Another 6 rats exposed to neither glycerol nor contrast media served as controls. The effect of ioxilan and saline on the albumin excretion was similar, whereas diatrizoate and iohexol increased it significantly. The contrast media had no further inhibitory effect on the reabsorption of glucose. Iohexol caused significantly increased excretion of all three enzymes, ioxilan of NAG and LDH, whereas diatrizoate only increased the excretion of LDH. The sodium excretion was further increased by ioxilan and diatrizoate, whereas none of the contrast media affected the phosphaturia. Both ioxilan and iohexol caused a round cell response around the tubules shown by light microscopy whereas diatrizoate caused no further changes. It is concluded that diatrizoate and iohexol increase glomerular dysfunction induced by glycerol i.m.; all three contrast media cause some further increase in the tubular dysfunction. Neither diatrizoate, iohexol nor ioxilan prolong nephropathy induced by glycerol i.m. determined by the chemical analyses. The histologic finding indicates a direct toxic effect of non-ionic low osmolar contrast media in this animal model of nephropathy.

Animals↗
PubMed1988

Comparison of the toxicity of the radiocontrast agents, iopamidol and diatrizoate, to rabbit renal proximal tubule cells in vitro.

Radiographic contrast agent-induced acute renal failure is an increasingly recognized clinical event. Multiple factors have been implicated in its development. Recent experiments have demonstrated that sodium diatrizoate, a common ionic radiocontrast agent, is moderately toxic to proximal tubule cells in vitro, and that this toxicity is enhanced by hypoxia. In this study, we compare toxicities of the nonionic radiocontrast agent, iopamidol, and the commonly used ionic contrast agent, diatrizoate. Suspensions enriched in proximal tubule segments were exposed for 82.5 min to 10 or 25 mM diatrizoate or 10 or 25 mM iopamidol with or without 22.5 min or 30 min of hypoxia. Cell viability parameters, including basal and uncoupled respiratory rates, tubule cell potassium and calcium levels and cell ATP content were measured. No consistent differences in tubule viability parameters were observed between tubule suspensions exposed to 10 mM concentrations of the radiocontrast agents during either oxygenated or hypoxic conditions. Under oxygenated conditions, both 25 mM iopamidol and diatrizoate exposure produced greater metabolic alterations in renal tubules than control conditions, but the effects were not statistically significant. With concomitant hypoxia, the alterations after 25 mM diatrizoate exposure were significantly greater than those seen after exposure to 25 mM iopamidol. Iopamidol had less of a detrimental effect on renal tubule potassium content and both basal and uncoupled respiratory rates than that of diatrizoate under these conditions. Thus, diatrizoate is more toxic to rabbit renal proximal tubule cells than iopamidol in vitro, and this difference in toxicity is enhanced by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMedDate not supplied

Simple 1H NMR spectroscopic method for assay of salts of the contrast agent diatrizoate in commercial solutions.

A simple, accurate, and specific 1H NMR spectroscopic method was developed for the assay of diatrizoate meglumine or the combination diatrizoate meglumine and diatrizoate sodium in commercial solutions for injection. A mixture of injectable solution and sodium acetate, the internal standard, was diluted with D2O and the 1H NMR spectrum of the solution was obtained. Two approaches were used to calculate the drug content, based on the integral values for the -N-CO-CH3 protons of diatrizoic acid at 2.23 ppm, and -N-CH3 protons of meglumine at 2.73 ppm, and the CH3-CO-protons of sodium acetate at 1.9 ppm. Recoveries (mean +/- standard deviation) of diatrizoic acid and meglumine from 10 synthetic mixtures of various amounts of these compounds with a fixed amount of internal standard were 100.3 +/- 0.55% and 100.1 +/- 0.98%, respectively. In addition to providing a direct means of simultaneously assaying diatrizoic acid and meglumine, the proposed NMR method can also be used to identify diatrizoate meglumine and each of its molecular components.

Contrast Media↗
PubMed1983

Hemodynamic changes induced by cardiac angiography with ioxaglate: comparison with diatrizoate.

The hemodynamic and electrocardiographic changes induced by left ventriculography and coronary arteriography with ioxaglate (a new low osmolality angiographic contrast agent) were characterized and compared with the changes induced by a commercial formulation of the commonly used angiographic contrast agent, diatrizoate (Renografin-76). Left ventriculography and coronary arteriography were performed in 25 patients utilizing ioxaglate and in another 25 patients utilizing diatrizoate. Both agents increased left ventricular end-diastolic pressure and decreased arteriovenous oxygen difference after left ventriculography, but the magnitude of the increase caused by ioxaglate was significantly less than that caused by diatrizoate (changes in left ventricular end-diastolic pressure was 5.3 +/- 1.3 mm Hg with ioxaglate and 9.5 +/- 1.5 mm Hg with diatrizoate [p less than 0.02] ). Change in arteriovenous oxygen difference was -0.33 +/- 0.19 ml/100 ml with ioxaglate and -0.85 +/- 0.13 ml/100 ml with diatrizoate (p less than 0.05). Both agents were well tolerated when used for coronary arteriography with no adverse events occurring in either group. Ioxaglate is a well tolerated cardiac angiographic contrast agent that produces less hemodynamic disturbance than diatrizoate. Accordingly, it may be particularly well suited to use in patients with impaired left ventricular function.

Adult↗
PubMedDate not supplied

Failure to prostaglandin A1 to modify renal diatrizoate uptake in experimental acute renal failure.

Acute renal failure (ARF) was induced in rats by intramuscular injection of glycerol. Forty-eight hours later prostaglandin A1 (PGA1) in a dose of 1, 5 or 25 microgram/kg bodyweight or phosphate buffer was infused intravenously over 15 min into these animals and controls. After 14 min, 125I-labeled diatrizoate was injected intravenously in a dose of 15 mg/kg bodyweight. Uptake and distribution of diatrizoate were measured one minute later in whole kidneys or kidney slices to provide indices of glomerular filtration. Diatrizoate concentrations were also measured in liver, plasma and washed red cells. Plasma volume was estimated with 125I-labeled albumin. PGA1 produced a dose-related increase in plasma diatrizoate concentration in ARF which was not accounted for by changes in uptake by the kidney, liver or red cells or by changes in plasma volume. It exceeded the relatively small increase in diatrizoate uptake which occurred in the kidney. Intrarenal distribution of diatrizoate did not change. These observations in the kidney suggest that intravenous PGA1 does not improve glomerular filtration in this model of established ARF.

Acute Kidney Injury↗
PubMedDate not supplied

Deleterious synergism of a cardiac glycoside and sodium diatrizoate.

Studies were performed in mice to determine if the cardiac glycoside, Strophanthin-K, and the contrast medium, sodium diatrizoate, interact synergistically to produce death. Intravenous injections of lethal and near lethal doses of the two agents produced a significantly greater mortality than the individual agents alone. Low or near clinical doses of Strophanthin-K, when given with doses of diatrizoate in the lethal range, produced mortalities significantly greater than did the diatrizoate alone. Similarly, low or near clinical doses of diatrizoate given with doses of Strophanthin-K in the lethal range produced mortalities significantly greater than for the Strophanthin-K alone. Isotonic or hypertonic saline, when substituted for diatrizoate or Strophanthin-K did not produce synergistic increases in mortality. Thus neither the injection volume, nor agent hypertonicity or ionic strength, seem to be the primary factors in the synergism to produce death. The diatrizoate anion appears to be an important factor. Until more information is available from other animal models it appears that patients receiving cardiac glycoside should be considered to have a higher than normal risk of serious reactions to contrast media in intravenous urography.

Animals↗
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↗
PubMed1988

Reduced cerebrospinal fluid production in the rat and rabbit by diatrizoate. Ventriculocisternal perfusion.

The effect of the radiographic contrast agent diatrizoate on cerebrospinal fluid (CSF) production was determined by ventriculocisternal perfusion. The lateral ventricle and cisterna magna of anesthetized rats and rabbits were cannulated stereotactically and perfused continuously with a H-3 inulin-labeled artificial CSF solution. Baseline collections of CSF began after steady state outflow was established; then, diatrizoate was administered intravenously for 1 hour. The baseline rate of CSF production was compared with that measured during and after the diatrizoate infusion. The baseline CSF production rate was 3.7 +/- 0.1 and 18.6 +/- 1.4 microL/minute in the rat and rabbit, respectively. Diatrizoate decreased the CSF production rate to 2.9 +/- 0.1 and 13.9 +/- 0.9 microL/minute. This reduced rate continued for at least 90 minutes after the end of the diatrizoate infusion, averaging 3.0 +/- 0.1 and 12.0 +/- 0.6 microL/minute in the rat and rabbit, respectively. These results confirm that decreased CSF production induced by the intravenous administration of diatrizoate is not species specific and is observed with the ventriculocisternal perfusion method of measuring CSF production rates.

Animals↗
PubMed1996

Glomerular and tubular effects of contrast media diatrizoate and iopromide.

The aim of this study is to evaluate the nephrotoxicity of two contrast media (CM), with different physicochemical characteristics: diatrizoate (ionic high-osmolar), iopromide (nonionic low-osmolar). Intravenous urography was performed in 34 patients: 17 were examined with diatrizoate and 17 with iopromide, randomly assigned. Different parameters of glomerular and tubular function were measured before and at 6, 24, and 48 h after urography. Both contrast media induced a reversible increase of urine enzymes, which was significantly higher after diatrizoate. In particular, diatrizoate determined a relevant increase of brush border enzymes gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) and of cytosolic enzyme lactate dehydrogenase (LDH), while, after iopromide increases of urinary enzymes were less evident and were significant only for GGT and ALP. In addition, diatrizoate affected other tubular functions (clearances of phosphorus and uric acid) and slightly decreased glomerular function in a few patients. In no case did these glomerular and tubular effects have a clinical relevance. In conclusion, the nonionic low-osmolar contrast medium iopromide appeared less nephrotoxic than diatrizoate. The cost-benefit ratio needs further examination.

Alkaline Phosphatase↗
PubMedDate not supplied

Diatrizoate contrast agents: 2-amino-5-acetamido-, and 3,5-diamino-2,4,6-triiodobenzoates.

We have examined the metabolic behavior of several triiodobenzoic acid derivatives because of the observed mutagenicity and cytotoxicity of 3-amino-5-acetamido-2,4,6-triiodobenzoate (I) and 3,5-diamino-2,4,6-triiodobenzoate (II). Measurements were facilitated using iodine-131 (131I)-labeled compounds. Drug retention in rabbits was monitored with a gamma camera. Metabolic products were studied by column and thin-layer chromatography. 3,5-Diacetamido-2,4,6-triiodobenzoate (diatrizoate) was partially deacetylated by liver microsomes to I and II. II was transformed in part to another substance whose structure remains undetermined. About 1% of nominal doses of I, II, and diatrizoate were retained for several days following intracardiac injection in rabbits. The rabbit did not appreciably acetylate I to diatrizoate and converted some of II to a urinary metabolite which was similar to that formed by liver microsomes. I was present in human urine following excretory urography with diatrizoate, but II was not detected. Manufacturers of diatrizoate should further reduce the level of free aromatic amines in preparations of diatrizoate. A method of doing so is reported.

Animals↗
PubMed1991

The effects of high (sodium meglumine diatrizoate, Renografin-76) and low osmolar (sodium meglumine ioxaglate, Hexabrix) radiographic contrast media on diastolic function during left ventriculography in patients.

Although a majority of studies indicate superior hemodynamic and clinical profiles of low osmolar compared with high osmolar contrast media, the effect of these agents on diastolic left ventricular function has not been examined. We prospectively examined hemodynamic, electrocardiographic, and echocardiographic indices of left ventricular function in patients undergoing contrast ventriculography with a high osmolar, ionic, monomeric contrast, diatrizoate (Renografin-76) compared with a low osmolar, ionic, dimeric contrast, ioxaglate (Hexabrix). Thirty patients were randomized to each group. There were no clinical differences between the two groups. The decrease in systemic pressures was significantly greater with diatrizoate after left ventriculography (-38.5 +/- 3.5 versus -18.2 +/- 2.3, p less than 0.001) and selective left coronary angiography (-29.5 +/- 2.4 versus -17.4 +/- 2.6, p less than 0.001). In addition, left ventricular end-diastolic pressure increased significantly more with diatrizoate (7.3 +/- 0.9 versus 2.7 +/- 0.8 mm Hg for ioxaglate, p less than 0.001). QT interval prolongation occurred in both patient groups. Diatrizoate decreased systemic vascular resistance, and increased cardiac output and left ventricular ejection fraction more than ioxaglate, while simultaneously increasing left ventricular end-diastolic volume and altering the peak atrial filling velocity. Negative dp/dt (p less than 0.05), but not Tau, computed by the logarithmic or derivative methods, was reduced by diatrizoate. These data indicate that significant alteration of diastolic filling patterns occurs with high osmolar compared with low osmolar contrast agents. Although the clinical significance of this observation is currently unknown, these data further support the reported hemodynamic superiority of the low osmolar, dimeric contrast agent ioxaglate during contrast angiography.

Contrast Media↗