The effect of dehydration on the elimination of aqueous contrast media from the subarachnoid space.

The frequency of side effects and complications from aqueous myelography is increased by dehydration. To study the effect of dehydration on the elimination of water-soluble contrast medium from the lumbar subarachnoid space, we measured iodine concentrations in the cerebrospinal fluid, serum, and urine for 24 hours after myelography in "hydrated" and "dehydrated" monkeys. Dehydrated animals were fasted for 12 hours prior to and 24 hours after myelography; hydrated animals received oral fluids ad libitum and 300 ml of intravenous fluids. Dehydrated animals had a lower concentration of contrast medium in the blood than hydrated animals. Dehydration slows the elimination of aqueous contrast medium from the lumbar subarachnoid space.

Excretion of aqueous myelographic contrast media in animals undergoing a repeat myelogram.

The rate of elimination of contrast media may be a factor in side effects and complications of aqueous myelography. The authors studied the effect of a previous myelogram and arachnoiditis on the elimination of aqueous contrast media from the subarachnoid space. Serum and cisternal CSF iodine concentrations were measured after experimental myelography in subhuman primates. The transfer of the aqueous contrast media from CSF to serum was slowed and the circulation with the cerebrospinal fluid into the intracranial cisterns was increased by a previous myelogram or arachnoiditis.

Contrast and electrolyte dynamics of the intravenous pyelogram. II. Disparities in serum and urine concentrations of meglumine and anion.

Intravenous or intra-aortic injections of meglumine iothalamate in dogs indicate a slightly different tissue distribution and excretory pattern of the meglumine cation and the iothalamate anion. Differences in serum and urinary concentrations of these ions suggest some cellular penetration of the meglumine anion. In addition, there seems to be some evidence for both tubular absorption and tubular excretion of meglumine as a minor component in the renal excretion of this ion. No significant differences could be demonstrated for either urinary load or concentration when the sodium salts of iothalamate were compared to the methylglucamine salts.

Mechanism of renal excretion of various X-ray contrast materials in rabbits.

The excretory behavior of nine nephrotropic contrast agents with varying physicochemical properties such as charge, lipophilicity, and molecular size was investigated. Renal clearance in comparison with inulin was determined by means of the continuous infusion method. Each contrast agent was infused at three dose levels in four to six rabbits. The investigations show that tubular transportation in proportion to glomerular filtration decreases with increasing dosages of all the contrast agents. Thus, with the highest concentration in plasma all contrast agents are eliminated at more or less the glomerular filtration rate (GFR). After administration of the low dosages the following differences are found: 1) Net tubular secretion increases for the monomeric contrast agent acids with increasing lipophilicity, in the order diatrizoate congruent to iothalamate less than iodamide less than acetrizoate. 2) The clearance studies do not reveal any tubular secretion or reabsorption for a hydrophilic cationic contrast agent. 3) The nonionic contrast agents do not show net secretion. The more lipophilic they are, the more they are reabsorbed. 4) Two dimeric contrast agents also do not reveal any tubular secretion. They seem to be reabsorbed more than monomers with the same charge.

Osmotic effect and solubility of amipaque (metrizamide) in the gastrointestinal tract.

Loops of small intestine in seven rabbits were resected with intact pedicle and ligated at both ends after instillation of 0.5 ml of Gastrografin, Urografin 76%, Amipaque 370 mg I/ml, Amipaque 170 mg I/ml or physiologic saline. After half an hour, the amount of fluid in the loops containing Gastrografin and Urografin 76% increases about twice as much as in the loops containing Amipague with the same iodine concentration because of their greater osmolality. The differences between the loops with isotonic Amipaque (170 mg I/ml) and physiologic saline are not significant. Precipitation occurs when sodium and meglumine salts of diatrizoate, metrizoate, iothalamate, iocarmate and ioglycamate are mixed with 0.05 N HCl. No precipitation occurs with Amipaque, not even when the HCl concentration is as high as 1.2 N. Precipitation occurs when Gastrografin is added to gastric juices with low pH, but is not seen with Amipaque should be a suitable contrast medium for gastrointestinal examinations because of its low osmolality and toxicity and good solubility in gastric juice.

Sequential changes in the CT numbers of the normal canine kidney following intravenous contrast administration. I. The renal cortex.

Using a 30-second computed tomography (CT) scanner, the sequential changes in CT numbers of the kidney were determined in three healthy dogs after intravenous administration of sodium and meglumine diatrizoate and iothalamate. For all contrast media, the mean CT number of the cortex was greatest within 2 minutes of rapid intravenous administration. At doses comparable to those used clinically, a linear relationship was demonstrated between the amount of iodine administered (in mg/kg body weight) and the corrected peak mean CT number of the cortex, such that doubling the amount of iodine caused the corrected peak mean CT number of the cortex to approximately double. Following the peak, the mean CT number of the cortex gradually declined. For all contrast media, the corrected mean CT number to corrected peak mean CT number ratios at 5, 10 and 20 minutes were 58 +/- 3%, 39 +/- 3%, and 28 +/- 5% respectively. Our data suggest that rapid-sequence CT may be a valuable tool for evaluating the physiology of renal contrast media excretion.

Brain parenchyma penetration by intrathecal ionic and nonionic contrast media.

Metrizamide, a nonionic water-soluble contrast medium, has been shown to penetrate normal brain when injected intrathecally. Recently it was suggested that the complications following intrathecal metrizamide are directly related to the cerebral concentration reached. Metrizamide, both in experimental animals and clinically, is regarded as less neurotoxic than equivalent iodine concentrations of ionic contrast media. In this study the degree and depth of brain penetration of intrathecal metrizamide and methylglucamine iothalamate (Conray 280), using a similar iodine concentration (280 mg l/ml), was compared at 1 hr in adult greyhound dogs. The depth of penetration and concentration reached in the cortical gray matter was determined by coronal computed tomographic scanning of the brain after removal. No significant difference was found between the two contrast media, suggesting that the rate of diffusion across the cerebrospinal fluid-brain interface is similar and that the difference in neurotoxicity is not explained by a reduced concentration of contrast medium in the case of nonionic metrizamide, when compared with ionic methylglucamine iothalamate. Using Evans blue as a qualitative marker, no evidence of gross blood-brain disruption was demonstrated in the area of maximum penetration with either contrast medium.

Relative uptake of low- and high-osmolality contrast media in CT of brain tumors.

The magnitude and time course of contrast enhancement in spontaneous canine brain tumors was determined for two contrast agents: meglumine iothalamate and sodium meglumine ioxaglate. Tumor enhancement during contrast infusion and at 5, 10, 15, 30, and 45 min was measured using quantitative computed tomography. Blood iodine was measured using x-ray fluorescence. Peak contrast enhancement occurred during the infusion, and the magnitude was the same for both agents. Per gram of iodine infused, blood iodine was 12.4% higher with ioxaglate than iothalamate. The monoionic dimer ioxaglate is as effective as iothalamate for enhancement of canine brain tumors.

[The pharmaco-kinetics of angiographic contrast media with special reference to the extra-vascular spaces. Fundamental studies on dog for the characterisation of angiographic media. I The pharmaco-kinetics of various contrast media under conditions of constant infusion (balanced flow)]. / Pharmakokinetik angiographischer Kontrastmittel unter besonderer Berücksichtigung des extravasalen Raumes. Eine experimentelle Grundlagenstudie an Hunden zur Charakterisierung der Angiographica. I. Mitteilung:Pharmakokinetik verschiedener Kontrastmittel unter den Bedingungen der Dauerinfusion ("Fliessgleichgewicht")

The pharmaco-kinetics of angiographic contrast media in the extra-vascular space, which are largely unknown, were investigated experimentally in dogs. As part of a basic study, using radio-active contrast media, it was possible to determine the concentration and rate of elimination in practically all organs and tissues. Measurements were carried out first after prolonged infusion of the contrast under conditions of balanced flow, and secondly six hours after the end of the infusion. It was therefore possible to determine the inflow and loss of contrast medium in various organs, or organs systems. The most commonly used angiographic contrast media in Germany were investigated. Their kinetic behaviour is largely identical, their pattern of distribution and elimination depended principally on the organ or tissue. A comprehensive discussion of the results of all the experiments will be given in the third article.

Dynamic computed tomography of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism.

Dynamic computed tomography (CT) of the pituitary gland was performed in 55 dogs with pituitary-dependent hyperadrenocorticism (PDH) that underwent transsphenoidal hypophysectomy. On routine contrast-enhanced CT images, microadenomas of the pituitary gland often are indistinguishable from nontumorous pituitary tissue because of isoattenuation. Dynamic CT may allow visualization of these adenomas. The changes in the contrast-enhancement pattern of the pituitary during dynamic CT in 55 dogs with PDH were correlated with surgical and histopathologic findings. In 36 dogs, dynamic CT identified distinct contrast enhancement of the neurohypophysis (pituitary flush). In 24 dogs, this pituitary flush was displaced, which indicated the presence of an adenoma. This observation was confirmed surgically and histopathologically in 18 of the 24 dogs. In 19 dogs, there was a diffusely abnormal contrast-enhancement pattern. CT findings agreed with surgical findings in 13 of these dogs and with histopathologic findings in all 19 dogs. It is concluded that a dynamic series of scans should be included in the CT protocol of the pituitary gland in dogs with PDH because it allows for identification of an adenoma or a diffusely abnormal pituitary gland.

Renal excretion of contrast medium after endoscopic retrograde investigations.

Endoscopic retrograde investigations are often performed as diagnostic procedures. The investigation of urine after such procedures in 21 patients has shown that appreciable amounts of contrast medium can be excreted renally. No such excretion could be shown when the contrast medium was injected into the gut lumen. The fact that contrast medium can be absorbed into the liver the pancreas during endoscopic retrograde procedures should influence the decision to perform these studies in patients with known allergies.

Elimination of water-soluble contrast media from the subarachnoid space. Investigation with computer tomography.

Contrast media injected into the subarachnoid space may be eliminated in two different ways, by diffusion through the meningeal membranes or by transport through these CSF pathways. The latter mode of transport may be examined using computer assisted tomography of the head. Diffusion predominants with contrast media of low molecular weight, such as methiodal sodium. The transport through the CSF cihculation increases when contrast media of high molecular weight such as meglumine iocarmate and metrizamide are used.

The effect of position of patient on the passage of metrizamide (Amipaque), meglumine locarmate (Dimer X) and ioserinate (Myelografin) into the blood after lumbar myelography.

Lumbar myelography was carried out with the contrast media Amipaque, Dimer X and Myelografin in 10 patients each. Five of the patients treated with each contrast medium were kept in a sitting position after the examination, the others lay flat. Blood levels and excretion were measured up to 24 h. The results are interpreted as follows: 1. After lumbar injection of the contrast media there is a short phase of distribution in the subarachnoid space (lag time) and they then are transferred into the blood with a half-life of 3.9 +/- 2.4 h. The transport from the CSF is almost completed approximately after 24 h. The velocity of transport varies greatly between the individual patients. Watersoluble contrast media presumably flow passively with the CSF through the arachnoid villi into the venous blood. 2. The horizontal position of the patient reduces the lag time until the beginning of the actual transfer of the contrast medium. 3. The transfer of Dimer X begins somewhat later compared with Amipaque and Myelografin.

The transport of dimer-X to the subarachnoid cisterns and convexity of the brain in normal people: case reports.

Computerized axial tomographic scans were performed on 7 patients, 3, 8 and 20 hours after lumbar myelography with Dimer-X. This contrast agent was seen in the subarachnoid cisterns 3 and 8 hours after injection, and 24 hours after injection it had completely disappeared.

Hyperperfusion and enhancement in dynamic computed tomography of ischemic stroke patients.

The passage of contrast medium was observed using serial computed tomography (CT) in 24 stroke patients. Density--time profiles of various brain regions were plotted. In normal brain tissue, X-ray attenuation showed a maximum increase during the arterial phase (16.4 +/- 11.0%) and was 2.8 +/- 2.2% above control during stable distribution. In hypoperfusion, increase in attenuation was always below 10% in the arterial phase, while hyperperfusion was characterized by an attenuation increase of 25 to 70%. Enhancement was defined by a density increase of 16.8 +/- 14.8% and a tissue/blood ratio between 7 and 60%. An attempt was made to establish a relationship between the serial CT pattern and the prognosis. Enhancement tended to indicate severe morphological changes followed by permanent neurological deficit, whereas hyperperfusion was generally an indicator of probably recovery.

Radioisotope X-ray fluorescence technique in the study of joint inflammation.

An X-ray fluorescence technique was employed to study the clearance rate from the knee joint of an intraarticularly injected stable tracer. Clearance curves, determined in two normal volunteers and in three patients with various articular diseases, were found to be of the monoexponential type in agreement with results obtained by authors employing radioactive tracers. Clearance half-time values in basal conditions were higher in the normal knee joint than in the inflamed knee joint. The effect of a corticosteroid suspension injected into the knee joint was also studied. Preliminary results obtained indicate that the X-ray fluorescence technique can be employed, with some advantages compared with the radiotracer technique, for quantitative determination of spontaneous or pharmacologically induced changes in joint inflammation.

Tissue pertechnetate and iodinated contrast material in ischemic stroke.

Isotope uptake during static radionuclide scanning and contrast enhancement during CT scanning, which may result from similar pathophysiologic mechanisms after ischemic infarction, were investigated in an animal model. Infarction was produced by transorbital occlusion of the middle cerebral artery in cats killed one, 2, 4, 8, or 16 days later. Sodium pertechnetate containing technetium-99m and 30% methylglucamine iothalamate labeled with I-125 were administered intravenously 60 and 15 min respectively prior to sacrifice. A coronal section through the infarct was parceled into 30 portions which were assayed for concentration of each isotope. Adjacent brain was prepared for histopathologic correlation. Concentrations of the 2 materials were highest in infarcted brain at 4 and 8 days. Strong positive correlation was found between tissue concentrations of the 2 materials in all brain samples. Elevated tissue levels correlated with necrosis, macrophage infiltration, and vascular hyperplasia. The results support the probability that radionuclide scan positivity and CT contrast enhancement reflect the same pathophysiologic development, probably extravasation of the respective labels, after ischemic stroke.

Work in progress: reduction of calcium activity by radiopaque contrast media.

An in vitro examination of the effects of radiopaque contrast media anions, cations, additives, and ionic strength on ionic calcium level using ion-specific electrodes was made. The calcium-binding additives sodium citrate and sodium EDTA produced the largest reduction in ionic calcium. At the same iodine concentration the anions diatrizoate, iothalamate, metrizoate, and ioxaglate reduced ionic calcium by essentially the same amount. Sodium compounds reduced ionic calcium more than did meglumine compounds, a difference that is probably related to dissociation. The nonionic compounds iohexol and iopamidol did not reduce ionic calcium significantly. Ionic strength appears to have little direct effect on ionic calcium at and above physiologic levels. All ionic contrast media bind significant amounts of ionic calcium at the high concentrations achieved during selective arteriography. Since the anions are only weak calcium binders supplemental calcium can restore the level of ionic calcium.

[Study of intracranial dynamics by applying a water-soluble contrast medium, N-methylglucamine iothalamate, to the dog brain].

The water-soluble contrast medium, N-methylglucamine iothalamate (NMGI), when injected in a dose of 1 ml into the cerebral parenchyma space of dogs (Feldberg's method), diffused within the lateral ventricle at a constant rate of flow against the nerve fibers running therein. Such was recorded by X-ray television and 16 mm cinecamera. Injection of the same dose into the subarachnoid space, however, did not produce these phenomena. Differences in the mode of transfer from brain to heart as the result of three different sites of application (ventricle, parenchyma and subarachnoid space) were investigated using 131I labeled NMBI, the determination of radioactivity being made by two scintillation detectors situated at the head and the heart. The determination of RI activity revealed that the above mentioned three areas of brain have their own characteristic pattern of attenuation from brain to heart, particularly in the case of subarachnoid application. Clonic convulsions after intracranial administration of NMGI in dogs occurred when NMGI was given into the parenchyma but not when given into the ventricle.

Pharmacokinetics of contrast media: experimental results in dog and man with CT implications.

The pharmacokinetics of contrast media such as sodium iocarmate, sodium ioxithalamate, metrizamide, sodium/meglumine diatrizoate, and sodium ioxaglate (a recently introduced medium: a hexaiodinated monoacid dimer) was compared in 25 dogs. A biphasic phenomenon was observed due to the rapid diffusion of contrast media from plasma into tissue (interstitium) followed by slow urinary excretion. A bicompartmental analysis was performed in dogs for each agent, showing that the tissue distribution of ioxithalamate is higher than that of other media. Sodium/meglumine ioxithalamate, sodium iocarmate, and sodium/meglumine ioxaglate were also compared in 20 human subjects. The diffusion and excretion phases observed in man appear to be slower than in the dog. Significant variations of iodine plasma concentration from one patient to another were recorded for the same medium and at the same interval after injection. Significant differences were observed between ioxithalamate and iocarmate or ioxaglate plasma concentrations due to the greater tissue diffusibility of ioxithalamate. The mechanisms affecting contrast media diffusibility are discussed: osmolarity, liposolubility, protein binding, and molecular size. Variations in contrast medium concentration in plasma noted in different patients with the same medium are explained by variations in tissue distribution, contrast medium volume, patient age, and patient hydration. Some computed tomographic (CT) implications of these pharmacokinetic studies are discussed. The need for highly diffusible media in routine CT and for less diffusible media in CT angiography is emphasized.