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PubMed1992

Contrast media-induced renal morphologic lesions during experimental hemorrhagic necrotizing pancreatitis.

RATIONALE AND OBJECTIVES: Contrast media-induced renal morphologic changes were studied in rats. Hemorrhagic pancreatitis was induced as a means of sensitizing the animals to the effects of contrast media. METHODS: The histologically verified hemorrhagic pancreatitis was induced in Wistar rats (n = 66) by injecting 6% sodium taurocholate into the pancreatic duct. After 2 hours, the animals received intravenously 1.0 or 3.0 g iodine/kg of high-osmolal osmolal diatrizoate, low-osmolal iopromide or iohexol, iso-osmolal iotrolan or 0.2 or 0.6 g/kg of high-osmolal magnetic resonance contrast agent, gadolinium-DTPA (Gd-DTPA). Control animals received physiologic saline. The kidneys were fixed by perfusion 2 hours later, and the morphologic changes were reviewed by two independent observers blinded to the injected agent. RESULTS: The smaller dose of iohexol and the larger dose of all the contrast media induced a statistically significant (P < .001 or .01) cytoplasmic vacuolization in the proximal convoluted tubule (PCT) cells. The nonionic, low- and iso-osmolal contrast media caused as much or even significantly more vacuolization than diatrizoate. CONCLUSIONS: Hemorrhagic pancreatitis potentiates the contrast media-induced renal morphologic changes, which depend on the type and dose of the injected contrast media.

Animals↗
PubMed1993

Repeated intracoronary injections of contrast media. Additive hemodynamic and electrophysiologic effects in a dog model.

RATIONALE AND OBJECTIVES: Coronary arteriography in patients implies several selective injections into the coronary arteries. The authors investigate whether repeated injections cause additive cardiac hemodynamic and electrophysiologic effects in dogs. METHODS: Five repeated injections of 5 mL iohexol (Omnipaque 350 mgI/mL, Nycomed Imaging AS, Oslo, Norway), ioxaglate (Hexabrix 320 mgI/mL, Laboratory Guerbet, Cedex, France), and sodium meglumine-diatrizoate (Renografin-76 370 mgI/mL, Squibb Diagnostics, Princeton, NJ) were given into the left coronary artery in 7 anesthetized dogs and were compared with the effects after a 5 mL single injection of the same medium. Left ventricular (LV) pressures, LV dP/dtmax (inotropy) and epicardial monophasic action potential were recorded, from which monophasic action potential duration (MAPD) was measured. RESULTS: Repeated injections of ioxaglate and sodium meglumine-diatrizoate did not potentiate initial decrease in LV pressures and inotropy, but the secondary increase in LV inotropy increased more after repeated injections than after a single injection. Repeated injections of iohexol increased LV inotropy more than a single injection. All contrast media prolonged MAPD more after repeated injections than after single injections. MAPD was prolonged 30 sec after the last injection. CONCLUSION: Repeated injections of contrast media cause greater cardiac hemodynamic and electrophysiologic effects than a single injection during selective coronary arteriography.

Action Potentials↗
PubMed1993

Contrast bolus dynamic computed tomography for the measurement of solid organ perfusion.

RATIONALE AND OBJECTIVES: The authors have investigated the aortic responses to various intravenous bolus injections of nonionic and ionic contrast media and have presented data illustrating the potential of ultrafast computed tomography (CT) to quantify perfusion in the kidney, liver, and spleen. METHODS: Bolus Dynamics Study: Performed in 3 healthy dogs (weight: 35 kg to 36 kg). In 2 dogs, 15 mL of the nonionic agent iohexol and the ionic agent sodium-meglumine diatrizoate were injected at 5, 10 and 20 mL/sec via a venous catheter placed in the superior vena cava; the order of injection was alternated between the 2 dogs. In the third dog, 25 mL of iohexol 300 mg I/mL was compared with diatrizoate 370 mg I/mL with injection rates of 10 and 20 mL/sec. Computed tomography scanning at the level of the midabdominal aorta was performed using an ultrafast CT scanner. Time-density curves were drawn for regions of interest over the aorta, and gamma-variate fits performed. Perfusion Studies: Dynamic perfusion scans of the upper abdomen were performed in more than 50 patients. A dose of 25 mL of iohexol 300 mg I/mL was injected at 10 mL/sec via an intravenous cannula in the antecubital fossa, followed immediately by 25 mL of saline, at the same rate. Scanning was performed at a single level using an ultrafast CT scanner. Regions of interest were drawn and gamma-variate fits were applied to the vascular time-density curves. RESULTS: Bolus Dynamics: Excellent curve fits for aortic time-density curves were obtained. A 10-mL/sec versus a 5-mL/sec bolus produced an 8% higher peak density. Nonionic contrast increased the peak density by a mean of 6%, increased the area under the corrected time-density curve by a mean of 22%, and lengthened the increase time by a mean of 21%. Perfusion Studies: Values obtained were reproducible and correlated well with values predicted from inert gas washout techniques. CONCLUSIONS: Changes in the CT number in a region after an intravenous injection of contrast medium may be used to calculate blood flow per unit volume of tissue. Ultrafast CT offers sufficient data points for accurate calculation. The quality of the aortic bolus is of great importance. Nonionic media offer several important advantages: hemodynamic perturbation is minimized, and they are better tolerated at the high injection rates needed. Low-osmolality nonionic agents produce "better" curves than conventional high-osmolality ionic agents, all other factors being equal. The resulting data are relevant to intravenous digital subtraction angiography and indirect portography as well as to perfusion measurement. The technique of quantitative dynamic CT is theoretically applicable to any cross-sectional modality, notably magnetic resonance.

Animals↗
PubMed1995

Cardiac and hemodynamic tolerability of iodinated contrast media in the anesthetized rat.

RATIONALE AND OBJECTIVES: The study was designed to compare the hemodynamic effects of 11 iodinated contrast media (CM), including ionic (diatrizoate, ioxaglate), nonionic monomeric (iohexol, iopromide, iopamidol, iopentol, ioversol, iomeprol, ZK 139129), and nonionic dimeric (iotrolan, iodixanol) compounds. METHODS: Following left ventricular bolus injection of 1.2 g I/kg body weight in anesthetized rats, cardiohemodynamic parameters were measured. RESULTS: Compared with the control group, except for blood pressure (BP), all CM showed a similar response regarding the direction of the cardiohemodynamic changes after CM injection. A biphasic change in BP was observed for diatrizoate and iodixanol, whereas all other CM showed a transient increase in BP being most pronounced for ioxaglate. No arrhythmias were detected. The increase in LVEDP was lowest for the isotonic dimeric CM iotrolan and iodixanol. CONCLUSIONS: Only mild transient side effects were observed. Low osmolar, especially isotonic, dimeric CM show a clear benefit regarding cardiovascular side effects.

Animals↗
PubMed1996

Biochemical characterization of x-ray contrast media.

RATIONALE AND OBJECTIVES: Eleven ionic and nonionic contrast media were compared in parallel regarding their effects on various biochemical parameters in vitro. Partition coefficient, protein binding, release of histamine, hemolysis inhibition and complement activation were determined as well as inhibition of various enzymes. Additionally, incompatibilities between contrast media and intravascular drugs that often are coadministered were determined. METHODS: Partition coefficients were determined in the system n-butanol/water by spectrophotometry. Protein binding was measured by equilibrium dialysis. Histamine release from rat peritoneal mast cells was measured by radioassay. Hemolysis inhibition and complement activation was determined in beagle dog serum using antibody-coated sheep erythrocytes. The inhibition of enzyme systems was measured photometrically. Incompatibility with coadministered drugs was registered by appearance of precipitations. RESULTS: Hydrophilicity as determined by partition coefficients was highest for iotrolan and lowest for iotetrol. Protein binding ranged from practically zero for most substances to 14% for ioxaglate. Histamine release was highest for diatrizoate (77% at 100 mg I/mL) and lowest for iodixanol (1%). Complement activation at 100 mg I/mL ranged from 0% (diatrizoate, iopamidol) to 77% (iopentol). The inhibition of the enzyme systems urokinase, streptokinase, collagenase, tissue plasminogen activator, and lysozyme was lowest for the nonionic dimers. CONCLUSIONS: All compounds influenced the parameters tested. However, the degree of interaction was different. Although there was no significant correlation between hydrophilicity (partition coefficient) or osmolality and the tested parameters, nonionic dimers seemed to be superior to nonionic monomers. The reason might lie in reduced chemotoxicity of this class of contrast media.

1-Butanol↗
PubMed1998

The effect of some iodinated contrast media on human plasma butyrylcholinesterase activity.

The effect of three iodinated contrast media (CM) on human plasma butyrylcholinesterase (BuChE) activity was studied during the intravenous pyelography (i.v.P). BuChE is an enzyme that participates in the metabolism of acetylcholine and hydrolyzes food esters and drugs such as nondepolarizing muscle relaxants and local anesthetics. The three CM were: diatrizoate (an ionic substance) and iohexol and iopentol (two nonionic substances). Five minutes after the intravenous injection, iohexol reduces BuChE plasma activity by 8.5% but this effect disappears within 15 minutes. Diatrizoate and iopentol decrease BuChE plasma activity by 8% and 15.2%, respectively, 5 minutes after the injection and this effect remains stable for the next 15 minutes. The underlying mechanism is unknown. Plasma BuChE activity remains within the normal range in any case and no association with side effects can be made. Thus, according to the above findings, it is not possible to connect or exclude any relationship between BuChE plasma activity and CM-derived adverse reactions during the i.v.P.

Aged↗
PubMed1998

Influence of contrast media on the response of rat renal arteries to endothelin and nitric oxide: influence of contrast media.

RATIONALE AND OBJECTIVES: Contrast media (CM) such as diatrizoate meglumine (DTZ) or iohexol can cause renal vasoconstriction in vivo, and this may initiate CM-induced nephropathy. Endothelin-1 (ET-1), a vasoconstrictor, and nitric oxide, a vasodilator, are key modulators of renal circulation. We tested the hypothesis that CM enhances arterial responses to ET-1, or diminishes responses to nitric oxide. METHODS: A video dimension analyzer continuously recorded changes in diameter of isolated, pressurized rat interlobar renal arteries (200-400 microm diameter) superfused with combinations of CM, ET-1, nitric oxide, and other vasoactive agents. RESULTS: Superfusion of arteries with 3.3% DTZ, but not with 3.3% iohexol, enhanced their sensitivity to ET-1 by approximately twofold, as assessed by shifts in concentration-response curves. Both DTZ and iohexol decreased the sensitivity of arteries to nitric oxide by approximately threefold. Neither DTZ nor iohexol affected arterial sensitivity to other vasoconstrictors (phenylephrine, potassium) or vasodilators (forskolin, diltiazem). CONCLUSIONS: Diatrizoate meglumine and iohexol may induce or augment renal vasoconstriction in part by causing selective alterations in arterial sensitivity to ET-1 and to nitric oxide.

Analysis of Variance↗
PubMed1998

Prevention of contrast medium-induced renal vasospasm by phosphodiesterase inhibition.

RATIONALE AND OBJECTIVES: This study investigated the involvement of cyclic adenosine monophosphate (cAMP) in contrast medium-induced renal vasomotor effects and the efficacy of selective phosphodiesterase (PDE) inhibitors influencing cAMP in preventing contrast medium-induced renal vasospasm. METHODS: Isometric contractions of rabbit renal artery rings were subjected to increasing concentrations of the ionic contrast medium sodium/meglumine diatrizoate (DIA) and the nonionic contrast media iopamidol (IOP) and iodixanol (IOD) and compared with a potassium chloride control. Subsequently increasing concentrations of the nonselective phosphodiesterase inhibitors theophylline and papaverine and the following selective phosphodiesterase inhibitors were applied: vinpocetine, trequinsin, zardaverine, rolipram, and dipyridamole (subtypes I-V) before restimulation of the arterial tissue with contrast medium. RESULTS: Diatrizoate, iopamidol, and iodixanol induced contractions up to 30%, 15%, and 3.5% of the potassium chloride control, respectively. All phosphodiesterase inhibitors markedly inhibited the contrast medium-induced contractions in a dose-dependent manner. The selective phosphodiesterase inhibitors rolipram and trequinsin attenuated these contractions significantly more (92% and 94%) than did zardaverine, dipyridamole, and vinpocetine, with an inhibitory potency of 37%, 41%, and 62%, respectively. CONCLUSIONS: Nonionic contrast media induced renal vasoconstriction less potently than ionic contrast media. Significant differences in the ability to prevent contrast medium-induced vasoconstriction were observed among the various phosphodiesterase subtypes studied. selective phosphodiesterase inhibition with inhibitor subtypes II and IV showed the most promising results in specifically preventing contrast medium-induced renal vasospasm.

Animals↗
PubMed1982

Value of high contrast medium dose in brain CT.

Fifty-five patients with brain lesions were examined by computed tomography (CT) after two doses of contrast medium: a bolus injection of 65% meglumine diatrizoate, 1 ml/kg, and a bolus injection of 65% meglumine diatrizoate, 1.5 ml/kg, in combination with an infusion of 250 ml meglumine iodamide containing 110 mg I/ml. The studies were usually performed 2 days apart and were analyzed by three radiologists. In 25 patients, one or more of the radiologists changed the diagnosis or the number or size of the lesions when the two scans were observed separately. In three patients, the primary tumor or metastases were seen in the study performed after the higher dose only, and, in two other patients having cerebral metastases, a greater number of metastases were detected in the high dose study. The lower dose containing 15 to 31 g iodine (306 mg iodine/kg) seems to be inadequate in CT of the brain.

Brain↗
PubMed1995

Nucleus pulposus pulmonary embolism. A case report.

STUDY DESIGN: This postmortem case report describes nucleus pulposus pulmonary embolism occurring in a human. OBJECTIVES: Clinical, pathologic, and pathogenetic features of the case are discussed. Reference is made to warnings in the literature stressing the importance of avoiding, during radiologic procedures, any possibility of intrathecal ingress of iodinated, ionic, hyperosmolar contrast material. SUMMARY OF BACKGROUND DATA: Various tissues have been implicated as pulmonary emboli in humans. Nucleus pulposus has been reported to embolize to spinal cord vessels in animals and humans and to embolize to the lungs in two animal species. This is the first report of nucleus pulposus pulmonary embolism in a human. METHODS: A patient with refractory low back pain was admitted for lumbar discography using diatrizoate meglumine, 52%, and diatrizoate sodium, 8%. Afterward, an ultimately fatal systemic reaction began, among the symptoms of which were spasmodic extensions of the lower back and legs. Postmortem examination was performed. RESULTS: Nucleus pulposus pulmonary emboli were seen microscopically on random lung sections. The lumbar vertebral column grossly featured acute herniations of disc material into vertebral marrow spaces; nucleus pulposus was identified microscopically in these areas. CONCLUSIONS: We speculate that the spasmodic back extensions imposed compressive forces on vertebrae, causing nucleus pulposus to be extruded into vertebral marrow sinusoids (thus creating emboli) and possibly causing these emboli to flow anteriorly into the anterior external vertebral plexus, which resulted in pulmonary emboli exclusively with no spinal cord emboli.

Anaphylaxis↗
PubMed1989

The effects of water soluble contrast agents on the respiratory tract.

The water soluble contrast agents Gastrografin (Sodium diatrizoate and meglumine diatrizoate, Schering, Berlin), Iopamiro 300 (Iopamidol, Schering, Berlin), and Dionosil Aqueous (propyliodone BP, Glaxo, England) were instilled into the tracheobronchial tree of rats in doses of either 0.1 ml and 0.25 ml. Rats being used as controls, underwent sham operations with the instillation of air instead of contrast agent. In all, 85 rats were used. All rats that had not already died from the effects of contrast agent were sacrificed 30 minutes after instillation. The relative effects of the contrast agents were measured by comparing: 1. survival time; 2. radiographic effects of the contrast agents on the lungs and; 3. pathological changes as estimated by post mortem lung section and microscopy. The least toxic agent was the one with the lowest osmotic activity, namely Aqueous Dionosil. It is therefore recommended that Aqueous Dionosil be used in preference to Gastrografin or Iopamidol for studies of the oesophagus whenever there is a danger of aspiration of contrast agent into the tracheobronchial tree.

Animals↗
PubMed1983

Meconium ileus equivalent in older patients with cystic fibrosis.

Meconium ileus equivalent is one of the lesser known manifestations of cystic fibrosis, and occurs most often in older patients. With the improved overall survival of patients with cystic fibrosis, one would expect to see this condition more often in the future. Of 53 patients attending our cystic fibrosis clinic for adolescents and adults, eight had experienced a total of 25 episodes of meconium ileus equivalent. Recurrent attacks occurred in seven patients, of whom four had at least four separate, well documented episodes: these episodes were associated with obvious recognised precipitating factors in only three patients. All patients responded to appropriate medical treatment with acetylcysteine or sodium diatrizoate, including three who had previously undergone surgery for meconium ileus equivalent elsewhere. Controversies remain, however, concerning the role of prophylactic medical management with acetylcysteine, sodium diatrizoate, and pancreatic supplements.

Acetylcysteine↗
PubMed1976

Use of tissue culture to examine neurotoxicity of contrast media.

The effect of small concentrations of diatrizoate, ioglycamate, and iopanoate salts on cultured sympathetic ganglia was studied. Biliary contrast media in clinical blood concentrations caused severe degeneration of cultured neurons, but similar concentrations of diatrizoate caused no effect. This technique may be used to measure the direct neurotoxicity or general cytotoxicity of contrast media.

Animals↗
PubMed1983

Acute damage to human endothelial cells by brief exposure to contrast media in vitro.

Cultured endothelial cells derived from human umbilical cord veins were labeled with Na2 (51Cr)O4 and exposed to pure isoiodinated contrast media or control solutions for 10 minutes to simulate the effects of intravenous injections of contrast media on the human endothelium. Metrizamide, iohexol, iopamidol, meglumine/Ca metrizoate (300 mg I/ml), meglumine/Na diatrizoate, meglumine/Na ioxaglate, and meglumine/Ca metrizoate (200 mg I/ml) were tested. Iso-osmolal mannitol solutions were used to determine the portion of injury that was due to the effects of osmolality. Up to six times more chromium-51 was released from the cultures following exposure to the two hyperosmolal ionic contrast media (meglumine/Na diatrizoate and meglumine/Ca metrizoate) than with exposure to the least toxic agent, iopamidol. The dimer ioxaglate and the three nonionic agents (iohexol, metrizamide, and iopamidol) gave a chromium-51 release rate that was almost equal to or lower than that of 0.9% saline. Follow-up of the washed cultures for 24 hours showed no residual toxic effects.

Cells, Cultured↗
PubMed1986

Knee arthrography: effects of various contrast media and epinephrine on synovial fluid.

Changes in synovial fluid leukocytes, total protein, and total complement were studied in 58 patients after they underwent single contrast material-enhanced knee arthrography with ionic (sodium iothalamate, sodium meglumine diatrizoate, meglumine iothalamate) and nonionic (iopamidol, iohexol) contrast media. In 30 of 58 cases, 0.3 mg epinephrine was also injected. In patients examined without epinephrine, a significant increase in the number of leukocytes was observed when sodium iothalamate and sodium meglumine diatrizoate were used. When administered with epinephrine all ionic compounds produced significant leukocytosis; articular reactions were most evident in patients examined with sodium salts. No inflammatory changes in the synovial fluid were observed when nonionic compounds were used. These data suggest that sodium-containing compounds produce a greater reaction in the joint compared with other contrast media, nonionic compounds are better tolerated by the joint, and epinephrine increases the articular reaction to ionic contrast media.

Adolescent↗
PubMed1987

MR arthrography: anatomic-pathologic investigation.

To enhance the efficacy of magnetic resonance (MR) imaging in evaluating articular soft-tissue structures, arthrography was performed before imaging 45 fresh cadaveric specimens. Contrast agents used were gadolinium-DTPA, 0.9% saline, diatrizoate, and air. MR imaging was performed with and without intraarticular contrast material, and specimens were subsequently sectioned in the same plane. Gd-DTPA was the most effective agent. Saline and diatrizoate exhibited equivalent signal behavior and necessitated T2-weighted sequences, while air was not useful. Depiction of normal anatomy was enhanced with MR arthrography. After surgical creation of lesions in selected specimens, subtle tears were delineated exclusively with MR arthrography, and major tears were diagnosed more confidently. Intraarticular contrast material may enhance the diagnostic capabilities of MR imaging in the setting of joint disease.

Air↗
PubMed1988

Cutaneous reaction to contrast material.

Two children are described who developed an apparent cutaneous contact reaction to contrast material in urine. Both children had undergone uneventful voiding cystourethrography with diatrizoate meglumine injection USP 18% followed by intravenous urography with diatrizoate meglumine injection USP 60%. Approximately 1 hour after urography cutaneous bullae and surrounding erythema of the buttocks (one case) or foreskin (one case) were noted. This reaction resembled a superficial chemical burn.

Buttocks↗
PubMed1990

Risk of thromboembolism during diagnostic and interventional cardiac procedures with nonionic contrast media.

To investigate the relationship between clot formation and thromboembolism, canine blood was withdrawn into catheter-syringe or catheter-steerable wire systems containing either contrast medium or normal saline as used in debubbling techniques. The contrast media used were iohexol, iopamidol, ioxaglate, and diatrizoate. Without the use of heparin, after a 30-minute incubation, blood clots were harvested from all catheter-syringe systems except those with diatrizoate and from all catheter-steerable wire systems. Significantly more blood clot was harvested from the catheter-steerable wire system. With use of heparinized blood, no clot was found in any system. Twelve dogs that underwent coronary angiography were divided into two groups; one received heparin (5,000 IU) and the other did not. Thromboembolism occurred in all nonheparinized dogs that underwent angiography with iohexol or iopamidol but not in any other group. The authors found that in a dog model nonionic contrast media are more thrombogenic than ionic contrast media, especially in the catheter-steerable wire system. The blood clot in the catheters is associated with thromboembolism during angiography. The authors maintain that in this setting, blood clotting and thromboembolism with nonionic agents can be eliminated with heparin.

Animals↗