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Elimination of aqueous contrast media from the lumbar subarachnoid space was measured. Iodine concentrations in serum and cisterna magna cerebrospinal fluid were studied in animals undergoing myelography with metrizamide, iocarmate, Iopamidol, or P-297. We found that all four contrast media were eliminated rapidly into the serum and urine, and transported slowly into the basal cisterns.
A new aqueous myelographic contrast media, iopamidol, was compared to iocarmate and metrizamide with respect to the risk of arachnoiditis. Macaque monkeys underwent myelography with one of the three contrast media. Twelve weeks later, the animals were restudied with myelography, then sacrificed for histologic studies of the arachnoid. Results suggest that iopamidol is safer than iocarmate and equivalent to metrizamide with respect to the risk of arachnoiditis.
The effect of mildly and strongly hypertonic solutions on intestinal tone and motility was tested with aqueous contrast solutions and with mannitol as a control in 15 dogs. These experiments were repeated in animals premedicated with atropine sulfate and/or methysergide maleate. Intestinal motility was recorded on serial x-ray films. Tone and motility were estimated by variations of intestinal caliber and rate of transit of contrast solution, respectively. The results obtained contradict the currently accepted mechanism of action of iodinated contrast media on the intestinal tract, which assumes that the effect is osmotic like that of a saline laxative. Solutions of different osmolarity produce hyperperistalsis of the same magnitude. This effect begins rapidly after the onset of gastric emptying and much sooner than a significant osmotic fluid shift occurs. Atropine sulfate and methysergide maleate (serotonin blocker), when given individually, are incapable of completely inhibiting hyperperistalsis induced by hypertonic solutions. However, when these agents are given in combination, motility is completely inhibited. The evidence supports a serotonin role in the hyperperistalsis induced by hypertonic solutions, partly by direct action of serotonin on the smooth muscle cells and partly by indirect action on the intramural cholinergic ganglion cells. This concept offers a possible means of eliminating one of the adverse effects of aqueous contrast media on the gastrointestinal tract.
The authors sought to determine whether radionuclides could provide a reasonable estimate of differential renal function in five normal dogs and six dogs with unilateral segmental renal infarction. Glomerular filtration rate (GFR) of each kidney was measured by the standard technique using constant infusions of 99mTc-DTPA, iothalamate, and creatinine following ureteral catheterization. These results were correlated with total GFR estimated by bolus injection of 99mTc-DTPA and analysis of the plasma 99mTc-DTPA disappearance curve obtained by blood sampling. Differential GFR was then calculated by multiplying the total GFR from double exponential analysis of this curve (DTPA2) by each of three measures of differential function. These include the percent differential uptake of 99mTc-DTPA and 99mTc-DMSA in the posterior projection as well as the geometric mean of 99mTc-DMSA uptake. There were good correlations between differential GFR calculated from iothalamate clearances obtained at ureteral catheterization and all noninvasive methods involving radionuclides and DTPA2 (r = 0.85 - 0.99). Single exponential analysis of the 99mTc-DTPA plasma disappearance curve was less satisfactory. The authors suggest that measurement of total and differential GFR calculated from plasma clearance of 99mTc-DTPA and external counting may be a useful method with potential clinical applications.
The metabolism of ionic and nonionic contrast agents was examined in the rabbit and in humans by specific measurement of iodide present in urine at different time intervals after injection of high contrast medium doses. Interest was focused on the experimental model compound C-29, which was investigated using a 125I-labeled compound, permitting a study of iodide release and the appearance of other metabolites in serum, bile, and urine from rabbits. Large, quantitative, individual variations were found, but in most cases th urine collected from both rabbits and humans contained more iodide than had been injected. A mean of 0.07% of total injected iodine was found within three days after injection of the ionic contrast medium metrizoate. The results with rabbits indicated that this figure may increase to 1% using the nonionic media tested. Direct evidence of metabolism of C-29 was found in bile, where up to 35% of the total radioactivity present in the bile 4-6 hours after injection was identified as a metabolite.
Segmental reflexes in the spinal cords of cats anesthetized with chloralose were used to evaluate the neurophysiologic effects of radiographic contrast agents. The exposed lumbar spinal cord was bathed with concentrations of ionic and nonionic agents including saline, sodium meglumine diatrizoate, meglumine iothalamate, meglumine iocarmate, and metrizamide. The following responses were evaluated: flexor and extensor monosynaptic reflex; polysynaptic flexion reflexes; spontaneous ventral root activity. Hypertonic solutions generally produced a transient decrease in all reflex activity for up to 1 hour. Isotonic solutions produced no significant changes in the monosynaptic responses, but an increase in amplitude of polysynaptic responses, and increased spontaneous activity. The usual facilitory effects of flexion reflex on the flexor monosynaptic reflex were unchanged, but the expected inhibitory effect of flexion reflex on the extensor monosynaptic reflex was changed to excitatory. The relative ability to produced these effects was sodium meglumine diatrizoate greater than meglumine iothalamate greater than meglumine iocarmate greater than metrizamide.
Both ionic and nonionic, monomeric and dimeric contrast media were found to release serotonin from intact human platelets in vitro. The monomeric contrast media were compared at the concentration range of 25 mg I/ml. Iothalamate was the strongest and the statistically equal metrizamide iopamidol, and P-297 were the weakest releasers. Monomeric and dimeric contrast media were compared at concentration ranges of 50 and 100 mg I/ml. They ranked, in descending order of serotonin releasing potency: iodipamide, iothalamate, P-127, iopamidol, and a statistically indistinguishable group of the monoacid dimer P-286, the nonionic dimer ZK 74 435, and metrizamide. The capability of contrast media to release serotonin seems to be a composite result of their specific physical and molecular structural properties.
Following 24-hour fasting and fluid deprivation, sequential changes in CT numbers of the canine kidney were determined in 4 dogs, each of whom received, at intervals, IV sodium diatrizoate, metrizamide, iopamidol, and sodium ioxaglate at a dose of 500 mgI/kg body weight. The urinary bladder was catheterized for baseline determination of urine osmolality and, subsequently, urine volume and CT number, CT number of the bladder urine from 0 to 10 minutes and from 10 to 20 minutes post-injection was obtained by scanning known dilutions of urine in vitro. Peak renal cortical enhancement occurred within 2 minutes of bolus injection and was not dependent on the chemical make-up of the contrast agent. Peak medullary enhancement occurred within 3 minutes of bolus injection. Peak medulla CT number following sodium diatrizoate was significantly less than that following metrizamide (P less than 0.025) or iopamidol (P less than 0.01). Peak medulla CT number was significantly less following sodium diatrizoate (P less than 0.01), metrizamide (P less than 0.01) and iopamidol (P less than 0.05) than following sodium ioxaglate. Urine iodine concentrations followed a similar pattern, with significant differences as follows: sodium diatrizoate less than metrizamide = iopamidol less than sodium ioxaglate. It was concluded that the investigational agents metrizamide, iopamidol, and sodium ioxaglate have theoretical advantage for excretory urography. Differences in renal handling of these agents are detectable, with CT scanning as differences in renal medullary enhancement and urine iodine concentration.
A method for quantification of aversion conditioning in rats was adapted to assess intrathecal neurotoxicity of contrast media (CM). Metrizamide, iopamidol, nonionic dimers DL-2-87 and DL-3-117, experimental iodophenyl glucose ethers DL-2-98 and DS-1-132, and Ringer's solution were injected into non-anesthetized rats drank water mixed with their preferred flavors, and subsequently were injected with 22.5 and/or 45 mgI/kg (200 and/or 400 mgI/ml concentration). From the intake of the preferred flavored water, expressed as percentage of total fluid intake consumed during a preference test and during a subsequent free choice test, a percentage avoidance/preference score was calculated as a measure of conditioning. At 12.5 mgI/Kg level, DL-2-87, which unexpectedly precipitated from solution in vivo, caused the most aversion, followed by metrizamide. The remaining compounds induced no significant aversion and were statistically indistinguishable from one another. At 45 mgI/kg dose level, all monomeric CM induced aversion of a statistically equal degree, while DL-3-117 proved nonaversive, equal to Ringer's solution.
Acentric chromosome fragments produced in cells by irradiation or other agents give rise to micronuclei in daughter cells. The micronuclei can be readily counted in large numbers of cells thereby providing a sensitive measure of chromosome aberrations. Previous studies have shown a consistent elevation of micronuclei count following the use of diatrizoate contrast materials. This study was undertaken to compare the micronuclei counts of patients receiving sodium iothalamate with those receiving sodium diatrizoate. Our results indicate that sodium diatrizoate produced significantly greater cytogenetic damage than the sodium iothalamate agents.
In a previous study using dogs whose renal function was rendered asymmetric by unilateral infarction, the efficacy of technetium-99m (99mTc) DTPA and DMSA in measuring differential glomerular filtration rate (GFR) was demonstrated. The present study was undertaken to determine whether the same techniques were applicable to unilateral ureteral obstruction. Five normal dogs and nine dogs with partial unilateral ureteral obstruction had determination of glomerular filtration rate by standard techniques using constant infusions of iothalamate and creatinine after ureteral catheterization. These results were compared with total GFR as measured by single injection of 99mTc DTPA and analysis of the plasma disappearance curve. Calculated differential GFR was obtained by multiplying total GFR from double exponential analysis of this curve (DTPA2) by each of three measures of differential function. These included the percent differential uptake of 99mTc DTPA and 99mTC DMSA in the posterior projection as well as the geometric mean of 99mTc DMSA uptake. There were good correlations between differential GFR determined by iothalamate clearances at ureteral catheterization and all noninvasive methods involving radionuclides and DTPA2 ( r = 0.93-0.99). Single exponential analysis of the 99mTc DTPA plasma disappearance curve was less satisfactory than double exponential analysis. These results and those reported previously support the use of radionuclides in the determination of differential GFR in a variety of clinical situations.
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Digital subtraction angiography (DSA) technology can now visualize many significant arterial structures from intravenous injections of contrast media. Image quality of these DSA studies is related to contrast agent enhancement. This study compares contrast agents of differing iodine concentration, viscosity, and osmolarity. A technique is described that utilizes a scanned projection digital radiographic system to compare quantitatively degrees of intra-arterial opacification after the administration of six intravenous contrast agents: iothalamate (at four different concentrations and in combinations with two different cations), diatrizoate, and ioxaglate. The quantitative arterial enhancement was compared in dogs utilizing an extra-period latin-square multiple change-over clinical trial design. The contrast agents span a range of organically bound iodine from 282 mg I/ml. When rate and volume of contrast agent injected are held constant, intra-arterial opacification is directly a function of the iodine concentration (mg I/ml) of the agent injected, while osmolarity and viscosity have no effect on opacification. These studies support the use of agents with high iodine concentration for maximum vascular visualization.
In the arterial wall, ATP:creatine N-phosphotransferase (E.C.2.7.3.2) is present in the form of its three isoenzymes, MM, MB, and BB, the latter being predominant. Six iodinated contrast agents in routine angiographic use were examined from the point of view of their effects in vitro on the isoenzymes of ATP:creatine N-phosphotransferase from the arterial wall, compared with their effects on the same isoenzymes in other organs. There is a clear inhibitory effect from the contrast agents on all organs, but it is least marked for the arterial wall. Furthermore, nonionic compounds have far less enzyme-inhibitory effect than ionic compounds.
In the first few hours after acute coronary thrombosis, clinical coronary angiography is associated with enhanced risk of ventricular fibrillation. In these experiments, the ventricular fibrillation threshold (VFT) was measured in anesthetized dogs before and during acute occlusion of the left circumflex coronary artery. Ischemia alone reduced the fibrillation threshold. Angiography with 1- or 2-ml does of Renografin 76 lowered VFT significantly more than did equal doses of iohexol or iopamidol. It is concluded that nonionic agents may be safer for coronary angiography in the presence of acute coronary insufficiency.
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The osmotic effects caused by conventional and low osmolality radiopaque agents have been studied in the isolated perfused canine kidney. Changes in vein flow, hematocrit, osmolality, and iodine content were measured at injection doses of 0.25 and 0.5 ml/kg (300 mgI/ml). Increases in osmolality and decreases in hematocrit were significantly greater with the conventional ionic monomer meglumine/sodium diatrizoate than with the low osmolality agents iohexol, iopamidol, and ioxaglate. The standard renal vein flow response for all agents was an increase (loss of renal water) followed by a decrease (gain of renal water). Diatrizoate produced the greatest increase in outflow at 0.25 ml/kg, but the differences between agents were not statistically significant. At the 0.5 ml/kg dose the differences in peak renal vein flow between agents were negligible. Renal vein iodine was highest with the dimer, ioxaglate and lowest with the diatrizoate. The nonionics iohexol and iopamidol produced essentially the same renal vein iodine levels and clearance. The new low osmolality agents have significantly less effect on osmolality and hematocrit and produce higher venous iodine levels than a conventional ionic monomer. The only difference between the low osmolality agents was the higher venous iodine seen with the dimer ioxaglate.
Contrast enhancement (CE) of the aorta, liver, and spleen was studied in dynamic body computed tomography (CT) in 71 patients. Four contrast media (CM) (diatrizoate, ioxithalamate, ioxaglate, iopamidol) were injected intravenously in equal bolus doses of 18.5 g iodine. Iopamidol produced the highest average peak and 2-minute aortic CE, significantly different from ioxithalamate (P less than 0.001), diatrizoate (P less than 0.01), and ioxaglate (P less than 0.0125) at peak levels. Two-minute CE values of the aorta were highest with iopamidol as were peak and 2 minute CE of the liver and spleen. A linear, inverse relationship between body weight and CE was present both at peak CE and after 2 minutes in all tissues. The nonionic CM appear to have best dose efficiency in the vascular phase of dynamic CT. These results are also applicable to digital angiography. Differences in the CE of parenchymal organs with different CM are so small that they are unlikely to have clinical significance.