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In an effort to evaluate the "spillover method" of measuring blood flow during angiography, we explored the effects of rapid injection of diatrizoate meglumine and diatrizoate sodium (Renografin-76) at rates no greater than resting blood flow in the superior mesenteric artery of anesthetized dogs. An increase in mesenteric blood flow and a decrease in mesenteric arterial pressure occurred many seconds after cessation of the injection. The dilation effected by the contrast agent was less marked at elevated blood flow values than at resting flows. The pattern of response to diatrizoate meglumine and diatrizoate sodium resembled that observed with vasodilator drugs. Our findings also suggest that the initial vascular response to a pulsation of the diatrizoate medium is vasodilation.
In 14 patients the kinetics has been studied of two contrast media labelled with 131I, and namely of MGM diatrizoate and of diatrizoate of sodium and MGM. The clearance was determined both at basal concentrations and in double concentration by means of external counting. The results were statistically studied by means of the linear regression method. The authors conclude that the MGM diatrizoate is exclusively eliminated through the glomeruli both in basal and double concentration. The diatrizoate of sodium and MGM is eliminated in low concentration through the glomeruli, while in double concentration it is partially eliminated through the tubuli.
The contractile effects of a commonly used radiographic contrast medium, sodium diatrizoate and meglumine diatrizoate, were examined on isolated canine renal arteries. Rings of renal artery, with and without endothelium, were mounted in organ chambers filled with Krebs-Ringer bicarbonate solution to record isometric tension. Both preparations contracted comparably to increasing concentrations (10(-9) to 10(-4) mol/L) of norepinephrine, and only rings with endothelium relaxed with the application of acetylcholine. The contractile responses of the rings to increasing concentrations of either contrast medium or osmotically matched solutions of glucose were similar, suggesting that the primary factor for contraction was the osmolality of the bathing solution. No significant differences were observed between the responses of rings with and without endothelium, suggesting that the endothelium did not influence the contractile response. After exposure to the hyperosmotic solutions, rings were again tested for relaxation with acetylcholine. Rings that were prepared with endothelium relaxed with the application of acetylcholine, suggesting that functional properties of the endothelium were not affected by the hyperosmotic media. The results of this study indicate that the vasoconstrictor effects of radiographic contrast media such as meglumine/sodium diatrizoate are related to increased osmolality and are not influenced by the presence of endothelium.
The ionic contrast medium diatrizoate used in high-dose unilateral nephroangiography in dogs produced an abnormal nephrogram, 'patchy contrast medium retention', and a marked decrease in renal blood flow in five of eight injected kidneys. Increased glomerular permeability (albuminuria), reduced glomerular filtration rate (creatinine clearance), and reduced osmotic diuresis were demonstrated in all selectively injected kidneys.
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The pathophysiology of radiocontrast agent-induced acute renal failure is presently unclear. To test for a possible direct deleterious effect of diatrizoate, a commonly used radiocontrast agent, on renal tubule cells, suspensions enriched in rabbit proximal tubule segments were incubated with sodium diatrizoate. After these manipulations, a variety of well-established metabolic parameters to quantitate the extent of cell injury were measured. Diatrizoate sodium (25 mM) produced significant declines in tubule K+, ATP, and total adenine nucleotide (TAN) contents, significant decreases in tubule basal and uncoupled respiratory rates, and a significant increase in tubule Ca2+ content, demonstrating the development of cell injury induced by diatrizoate. These effects were dose related and were progressive with increasing incubation time from 97.5 to 157.5 min. The effects of N-methylglucosamine (meglumine) on renal tubule cell viability was also evaluated. Meglumine is a low molecular weight amino-substituted cationic compound and is commonly added to radiocontrast dye solutions. Meglumine (25 mM) had significant effects to lower tubule K+ content and to decrease both tubule basal and uncoupled respiratory rates. These alterations were slightly additive to diatrizoate in that meglumine diatrizoate produced greater alterations in tubule-metabolic parameters compared to diatrizoate sodium. A period of 22.5 min of hypoxia also caused deleterious changes in each of these quantitative indices of cell viability, and diatrizoate potentiated the degree of hypoxia-induced cell injury. These results demonstrate that the radiocontrast agent, diatrizoate, is directly toxic to renal proximal tubule cells. Meglumine, a cation added to diatrizoate containing radiocontrast solutions, also had a moderate toxic effect on renal epithelial cells and added to the toxicity of diatrizoate. Diatrizoate also aggravated the degree of cell injury induced by a 22.5-min period of hypoxia. These experiments thus provide evidence for a direct toxic effect of diatrizoate on proximal renal tubule cells which was additive to hypoxic cell injury.
RATIONALE AND OBJECTIVES: Contrast media, especially high-osmolar ionic compounds elicit drastic effects on the microcirculation. In some areas of the microcirculatory network, blood flow decreases up to total stasis; in other areas, blood velocity increases. The authors studied the effect of the stable prostacyclin derivative, iloprost, added to the diatrizoate formulation on the number of perfused microvessels in the rat intestine. METHODS: Diatrizoate (600 mg iodine/kg) and increasing concentrations of iloprost, ranging from a total dose of 0 to 560 ng/kg, were injected intravenously into groups of four anesthetized male rats. The number of unperfused microvessels in the intestine were determined by in vivo microscopy. Each animal received two treatments at an interval of 35 minutes. One treatment consisted of diatrizoate alone, the other treatment consisted of diatrizoate plus iloprost. Two animals of each group received first diatrizoate alone and then diatrizoate plus iloprost. The other two animals first received diatrizoate plus iloprost and then diatrizoate alone. RESULTS: Diatrizoate alone reduced the number of perfused microvessels by 45%. The addition of iloprost resulted in a dose-dependent improvement of microcirculation. At a dose of 280 ng/kg, the effects of diatrizoate were completely abolished. Increasing the dose further diminished this effect. CONCLUSIONS: The addition of iloprost to diatrizoate eliminates the deleterious effects of diatrizoate on microcirculation.
We examined the acute systemic and renal hemodynamic effects of intravenous meglumine/sodium diatrizoate-76% and iopamidol in euvolemic and dehydrated dogs. The physiologic responses were compared with acute changes in the level of an endogenous heparin-like material (EHM). One of eight dehydrated dogs receiving diatrizoate (2 ml/kg) had an immediate vomiting reflex associated with a very significant decline in all measured renal hemodynamic parameters; none of eight dehydrated dogs receiving iopamidol experienced a similar reaction. EHM levels did not correspond to the magnitude of the physiologic responses following either iopamidol or diatrizoate. Significant differences between iopamidol and diatrizoate were noted when comparing the magnitude of the decrease in systemic pressure (- delta 3.8 +/- 3.02, iopamidol, n = 8; vs. - delta 19.4 +/- 7.3 mm Hg, diatrizoate, n = 8; P less than .03), increased renal plasma flow (+ delta 6.2 +/- 4.9, iopamidol, n = 8; vs. + delta 33.7 +/- 8.0 ml/min, diatrizoate, n = 8; P less than .05), and decreased filtration fraction (- delta 0.09 +/- 0.01, iopamidol, n = 8; vs. - delta 0.14 +/- 0.02, diatrizoate, n = 8; P less than .03). There was no significant difference in the decrease in glomerular filtration rate (- delta 7.4 +/- 1.0, iopamidol, n = 8; vs. - delta 9.3 +/- 1.3, diatrizoate, n = 8; P greater than .05), since the marked drop in filtration fraction occurring with diatrizoate was counterbalanced by the marked increase in renal plasma flow. Acute systemic and renal hemodynamic effects are significantly lessened when comparing iopamidol with diatrizoate.
Six hundred patients were prospectively randomized and given either diatrizoate meglumine 60 or iohexol 300 during dynamic contrast-enhanced body CT in order to compare image quality, contrast reactions, and the number of aborted studies or studies in which images had to be repeated. Three hundred two patients received iohexol 300, and 298 patients received diatrizoate meglumine 60. Thirty-nine percent (119/302) of the patients given iohexol 300 and 63% (188/298) of the patients given diatrizoate meglumine 60 had at least one adverse reaction thought to be related to contrast material during, or within 24 hr of, the body CT scan. When reactions of discomfort (heat or warmth, flushing, bad taste) were excluded, 16% (48/302) of the patients who received iohexol and 33% (99/298) of the patients who were given diatrizoate meglumine 60 had at least one adverse reaction. The differences in both types of reactions between the two agents were significant (p less than .001). Among scans evaluated for study quality, 71% (214/302) of the iohexol 300 group and 62% (184/298) of the diatrizoate meglumine 60 group had optimal enhancement (p = .02). However, when the optimal and adequate categories were combined, 301 of 302 patients given iohexol 300 and 292 of 298 patients given diatrizoate meglumine 60 had diagnostic-quality studies (no statistical difference). Studies were not terminated nor were images repeated in 97% (292/302) of the patients given iohexol 300 and in 94% (280/298) of those given diatrizoate meglumine 60. The CT study was repeated because of movement during the contrast injection or aborted because of contrast-related reactions in 0.7% of the patients given iohexol 300 and in 3.0% of the patients given diatrizoate meglumine 60. This difference was statistically significant (p = .04). Our results suggest that the difference in image quality, number of adverse reactions, and number of aborted/repeated CT scans performed with iohexol 300 or diatrizoate meglumine 60 are not sufficiently different to warrant conversion to nonionic agents for body CT scans.
The continual production and absorption of cerebrospinal fluid (CSF) provides for the dilution and removal of potentially toxic substances from the central nervous system (CNS). This study quantified changes in the CSF concentration of diatrizoate following pretreatment with various drugs that alter CSF production. Adult rats, pretreated with one of ten drugs or normal saline (control) and anesthetized, received sodium diatrizoate (2 mL/kg, IV). Blood and CSF were sampled 2 hours later, and the diatrizoate concentrations were measured. Serum diatrizoate levels in the control group averaged 144.3 micrograms/mL. There were no significant differences in serum levels between control and pretreated groups. The CSF diatrizoate concentration in the control group averaged 10.8 micrograms/mL. Pretreatment with acetazolamide, ritodrine, or probenecid resulted in a significant increase in the CSF concentration, to 24.7 micrograms/mL or 228% of control in the case of acetazolamide. Pretreatment with salicylate, carbachol, or aminophylline resulted in significantly lower CSF diatrizoate levels than control; 3.2 micrograms/mL (30% of control) for carbachol. Digoxin, furosemide, dibutyryl cAMP, or dexamethasone pretreatments had no significant effect on CSF diatrizoate concentrations. Thus, a wide range of drugs may significantly alter the concentration of diatrizoate in the CNS. Drug-induced changes in the rate of CSF production may be responsible for this action.
Image opacification, patients' tolerance, and clinical and laboratory findings were evaluated in patients having excretory urography at three centers. In a double-blind, parallel study, iopamidol was compared with diatrizoate (50-ml dose), and in an open-label trial, the administration of a 100-ml dose of iopamidol was evaluated. In the double-blind study, a total of 84 patients received 50 ml of either iopamidol or diatrizoate. In the open-label study, another 42 patients received a 100-ml dose of iopamidol. Image opacification scores after the administration of the 50-ml doses showed better opacification with iopamidol than with diatrizoate in the renal calices (p less than .05) and in the composite kidney (p less than .05). Opacification scores were higher for 100-ml doses of iopamidol than for 50-ml doses in all anatomic regions as well as in the composite kidney (p = .0001). Patients' tolerance to iopamidol was significantly better than their tolerance to diatrizoate (p less than .025). Investigators observed adverse drug reactions in a total of 10 patients. In the double-blind study, one of 43 patients had transient bradycardia after the administration of iopamidol. In the same study, four of 41 patients who received diatrizoate had five minor adverse drug reactions. With 100-ml doses of iopamidol, five of 42 patients had adverse reactions. No adverse side effects required therapy in either study. There were no significant changes in vital signs or laboratory values after drug administration. The results of this study show that iopamidol is a suitable agent for excretory urography at doses of 50 and 100 ml. Patients report fewer unpleasant side effects with iopamidol than with diatrizoate. Overall image quality was better with iopamidol than with diatrizoate. Overall evaluation of drug performance was better with iopamidol than with diatrizoate.
Leg venography with either 50% sodium diatrizoate or 60% meglumine diatrizoate was performed on 31 patients suspected of having deep venous thrombophlebitis. Four of 14 patients receiving meglumine diatrizoate experienced pain during venography, as compared to 14 of 17 patients receiving sodium diatrizoate (p less than 0.004). A second study showed no statistically significant difference in the incidence of pain between two groups of patients receiving either Renografin-45 (6% sodium diatrizoate, 39% meglumine diatrizoate) or Renografin-M-45 (45% meglumine diatrizoate).