Role of autocrine stimulation for the effects of cyclic AMP on protein and lipid phosphorylation in platelets activated by particles.

We have compared responses in platelets stimulated with the particulate materials, Intralipid (liposome-suspension) and a potential contrast medium IEEC (1'-(ethyloxycarbonyloxy)-ethyl-5-acetyl-amino-3-(N-methyl-acetyla mino)-2,4,6-triiodo-benzenecarboxylate coated with human serum albumin), with and without forskolin and inhibitors of autocrine stimulation (IAS: an ADP-removing system of creatine phosphate/creatine phosphokinase; RGDS to prevent fibrinogen/fibronectin binding to GPIIb/IIIa; SQ 29.548 as a TXA2 receptor antagonist; cyproheptadine as a serotonin receptor antagonist; BN 52021 as a platelet-activating factor receptor antagonist). The pattern of tyrosine-phosphorylated proteins, phosphorylation of initial lipids and phosphorylation of pleckstrin (P47) were used as markers for early signal transducing responses, while secretion of ADP+ATP and beta-N-acetyl-glycosaminidase were used as final responses. Intralipid showed no platelet activation except for some weak tyrosine protein phosphorylation that was inhibited by elevated cAMP. IEEC induced strong platelet activation that was partly inhibited by increased levels of cAMP and IAS. The inhibition of elevated cAMP seemed to be due to removal of the G protein-mediated activation from secreted autocrine stimulators either by IAS or forskolin. The remaining activity is a pure effect from IEEC which is not affected by elevated cAMP.

Cardiovascular and electrocardiographic effects of iopentol in left ventricular angiography. Comparison of the low-osmolar, non-ionic iopentol (Imagopaque 350) and the hyper-osmolar, ionic metrizoate meglumine-Na-Ca (Isopaque Coronar 370) in patients with coronary heart disease.

UNLABELLED: The aim of the study was to evaluate and compare the hemodynamic and electrocardiographic effects following injection of the non-ionic, low-osmolar contrast medium iopentol (Imagopaque 350, Nycomed Imaging AS, Oslo, Norway) and the ionic, hyper-osmolar contrast medium metrizoate meglumine-Na-Ca (Isopaque Coronar 370, Nycomed Imaging AS, Oslo, Norway) when used for left ventricular angiography. The study was performed in a double-blind, randomized manner in 82 patients with severe coronary heart disease. The patients who received iopentol experienced less adverse events and subjective discomfort of lesser intensity than those who received metrizoate (p = 0.0001). Both contrast media induced a biphasic change in left ventricular (LV) systolic pressure, with an initial fall followed by a prolonged rise, but the alterations were statistically significantly more pronounced with metrizoate than with iopentol. The changes in LV end-diastolic pressure (p = 0.023), and LV negative dP/dt (p = 0.002) were significantly more pronounced with metrizoate than with iopentol. Cardiac output and heart rate increased more with metrizoate, while stroke volume was equally increased by both agents. A prolonged increase in the QT-interval, throughout the 10-min observation period, was seen only after injection of metrizoate (p = 0.0006 for comparison between contrast media). CONCLUSION: Iopentol was well tolerated and induced markedly less severe hemodynamic and electrocardiographic alterations than did metrizoate in patients with severe coronary heart disease.

A comparison between IEEC, a new biodegradable particulate contrast medium, and iohexol in a tumor model of computed tomography imaging of the liver.

RATIONALE AND OBJECTIVES: Higher contrast between normal and pathologic tissues in the liver may enable detection of smaller lesions in computed tomography (CT). This can be obtained using a liver-specific contrast medium. The authors evaluate a new agent, IEEC (1'-Ethyloxycarbonyloxy)-ethyl-5-acetylamino-3-(N-methyl-acetylami no)-2,4,6- triiodo-benzenecarboxylate), in an animal model, as a potential contrast agent for CT scanning of the liver. The IEEC particulate contrast medium used is based on a prodrug ester design of metrizoic acid and accumulates rapidly in the liver. The particles are quickly degraded into well-known metabolites and excreted from the body. METHODS: Two groups of rabbits were inoculated with VX2-carcinoma directly into the liver by laparotomy. Computed tomography imaging studies were carried out 9 and 11 days after the inoculation. The investigation was designed as a crossover study. The first group was imaged both as controls (without contrast medium) and with the particulate contrast medium on the 9th day and with iohexol on the 11th day. The second group was imaged with iohexol on the 9th day and as controls, and with the particulate contrast medium on the 11th day. The contrast medium was administered in a dose of 100 mgI/kg. Iohexol was administered in a dose of 570 mgI/kg according to a standard clinical scheme in use at a radiology department for dynamic CT. Changes in normal liver/lesion contrast and the conspicuity of tumors were assessed. On completion of imaging studies on day 11, all animals were killed. The liver was removed and evaluated for the presence of tumors. RESULTS: At macroscopic inspection, all rabbits were found to have tumors ranging from 2 to 14 mm in diameter. The size and location of the tumors corresponded well with the CT images. In the images where the particulate contrast medium was used, the attenuation in the normal liver parenchyma and the contrast between normal liver and lesion was significantly higher compared with the images where iohexol was used or the controls. For all tumor sizes, the lesion detection capability with the particulate contrast medium was significantly higher compared with iohexol (P < .005) and controls (P < .05). CONCLUSIONS: VX2-carcinoma in rabbit liver is a useful model for studying the efficacy of contrast media in CT imaging. The particulate contrast medium IEEC improved visualization of liver tumors.

High performance liquid chromatography with multiwavelength detection: a technique for identification of iodinated x-ray contrast agents in human body fluids and brain tissue.

PURPOSE: Several cases of a severe adverse reaction, referred to as "ascending tonic-clonic seizure syndrome," have been reported after administration of water-soluble iodinated x-ray contrast agents for myelographic examinations. Because of the bizarre reactions, the identities of the causative contrast media were questioned. METHODS: Analyses of biologic materials from four of these patients were performed by using reverse-phase high-performance liquid chromatography. The chromatographic system was equipped with a fast-scanning UV-visible detector for the analysis of the UV-spectra of the chromatographic peaks. RESULTS: The analyses revealed that the nonionic contrast agents iohexol or ioversol were not present in detectable amounts in any of the samples. On the other hand, the chromatographic analyses revealed peaks that cochromatographed with and showed the same UV-spectra as the ionic agents diatrizoate, metrizoate, and ioxitalamate. CONCLUSION: The results indicate inadvertent injection of ionic contrast medium in all four cases.

Inadvertent intrathecal use of ionic contrast media for myelography.

PURPOSE: To describe instances of inadvertent intrathecal injection of ionic contrast media and to consider treatment approaches, and diagnostic and medicolegal issues. METHODS: Ten cases of inadvertent injection, of which nine were reported to the manufacturers/authors and one appeared in the literature, are related with emphasis on similarity of reactions. RESULTS: Six criteria are enumerated and used to coin the term "ascending tonic-clonic seizure syndrome." CONCLUSIONS: Therapeutic possibilities seem limited, but several methods for controlling seizures are suggested. The importance of identifying the contrast material is underscored. Awareness of the grave possibility of administering the wrong contrast material is the first step in avoiding this problem; awareness of the symptoms is the first step toward therapy.

The spectrum of isolated ocular reactions following intravascular contrast administration.

Five out of 2930 (0.2%) consecutive patients developed ocular adverse reactions following intravascular administration of sodium-meglumine diatrizoate. The adverse reactions included bilateral blurring of vision (2), unilateral orbital oedema (2) and bilateral intense conjunctival congestion (one patient). The latter two phenomena responded to steroid and antihistaminic agents. Contrast medium-induced ocular anaphylactoid response is rare but clinically significant.

Intracellular penetration and accumulation of radiographic contrast media in the rat kidney.

Radiographic iodine-containing contrast media (meglumine calcium metrizoate, iohexol and meglumine sodium ioxaglate) were injected intravenously in rats. At various intervals after exposure, in situ cryofixation of kidneys was performed. Thin, freeze-dried cryosections were examined by electron microscopy and X-ray microanalysis. In endothelial cells, erythrocytes and tubular cells high dry weight concentrations of iodine were found. Twenty-four hours after iohexol was injected, no trace of iodine was found in the plasma, microvilli or the nuclei of the tubular cells. Small organelle-like compartments in the cytoplasm of the proximal tubular cells contained high concentrations of iodine, whereas no iodine was found in the surrounding cytoplasm. Since no metabolism of contrast medium has been demonstrated, the iodine signals must be emitted from contrast medium molecules. Other elements were also measured, with the concentrations being always within the ranges found in tubular cells of control animals. The detection of intracellular contrast thus does not seem to be an artifact due to cell injury, but rather represents a physiological event in healthy cells in the rat kidney. Our results are in contradiction to the prevailing opinion that contrast media do not enter healthy cells. However, previous conclusions have been based on the use of conventional preparation methods, and the highly water soluble contrast molecules may have been lost during the different steps of fixation and processing.

Contrast enhancement of liver parenchyma and biliary tract related to liver function at delayed computed tomography.

Computed tomography (CT) of the liver was performed in 53 patients before, during and 4 to 6 hours after intravenous administration of approximately 60 g of iodine in metrizoate. At delayed CT, contrast medium was observed in the extrabiliary ducts in 20 patients (38%) and in the gallbladder in 28 (68%) of the 41 patients with no previous cholecystectomy. The increase in attenuation of liver parenchyma at delayed CT compared with the non-enhanced baseline CT ranged between 2 and 26 HU (mean 13.9). The material was divided into three groups with regard to liver function: normal, intermediate and pathologic. In the normal group contrast medium was observed in the gallbladder in 81 per cent and in the bile ducts in 57 per cent and the mean increase in attenuation of the liver parenchyma was 14.5 HU. In the pathologic group the same parameters were 40 per cent, 7 per cent and 10.6 HU, respectively. Contrast medium in the gallbladder and biliary ducts improved the information about anatomy. Pathology of the gallbladder and tumour growth along the hepatoduodenal ligament were better demonstrated. Delayed CT is a simple and non-invasive technique that may improve planning of liver surgery.

Comparison of non-enhanced, bolus enhanced, and delayed scanning techniques in computed tomography of hepatic tumours.

Non-enhanced, bolus contrast medium enhanced and 4 to 6 hours delayed computed tomography of the liver was performed in a prospective study of 53 patients. Forty patients had focal lesions, in 12 of these they were hypervascular. Contrast medium was administered as an initial bolus followed by a rapid injection of meglumine metrizoate (Isopaque Cerebral). The total iodine dose varied between 56 and 63 g, which gave an average increase in attenuation of 14 HU in normal parenchyma comparing delayed with non-enhanced scanning. Presence and extent of focal lesions were evaluated in a randomized and independent analysis by two radiologists. The percentage of examinations with correct tumour description was higher with bolus scanning (observer I 73%, observer II 75%) and delayed scanning (observer I 75%, observer II 78%) than with non-enhanced scanning (observers I and II 67%). An optimal bolus technique requires an exact timing of the contrast medium administration and scanning. Delayed scanning provides an excellent supplement when the bolus examination is suboptimal or shows equivocal findings.

Fulminant pulmonary edema following intravenous administration of radiocontrast media.

A 29-year-old woman who developed fulminant pulmonary edema several minutes after intravenous administration of radiocontrast media (RCM) is reported. The low pulmonary-capillary wedge pressure and the high protein concentration in pulmonary edema fluid indicated a noncardiogenic pulmonary edema related to increased lung vascular permeability. Laboratory studies showed a slight decrease of several complement components (C3, C4 and factor B) and a transient consumption coagulopathy. Potential pathophysiologic mechanisms involved in RCM- induced pulmonary edema are discussed.

Nephrotoxicity of contrast media in patients with diabetes mellitus. A comparative urographic and angiographic study with iohexol and metrizoate.

A double-blind urographic and angiographic study was done with the ionic contrast medium meglumine metrizoate and the non-ionic iohexol in 90 patients with diabetes mellitus. Twenty patients were insulin dependent, and 70 non-insulin dependent diabetics. Diabetic patients with decreased as well as normal renal function prior to the examination sustained a reversible and small increase in the plasma creatinine level postexamination. The small increase caused by meglumine metrizoate was significantly higher than the increase caused by iohexol. There was also a significantly higher increase in plasma creatinine among the patients with diabetic nephropathy compared with those without nephropathy.

Effects on the ATP content of cultured cells after radiographic contrast media exposure. Evidence for accumulation of contrast media in cultured cells.

The ATP content of cultured cells after exposure to meglumine-calcium metrizoate, sodium metrizoate, iohexol, iopamidol and saline was studied. Initially, the ATP content diminished rapidly for a short period and thereafter slowly during the incubation. After incubation with contrast media or saline, the ATP content slowly increased to normal when the cells were reincubated with fresh nutrient medium. Different contrast media and saline with the same final osmolality produced a similar effect on the ATP content of the cultured cells. Cellular association of meglumine-sodium diatrizoate, sodium metrizoate, sodium-iothalamate, iohexol and iopamidol was also examined. The established cell line NHIK 3025 as well as primary cultures of human umbilical endothelium were found to accumulate contrast media in a time- and concentration-dependent manner. When the incubation was carried out at 4 degrees C, the cellular accumulation of contrast medium was less than 35 per cent of that seen at 37 degrees C. It therefore seems that energy-dependent processes are involved to some degree.

Arthrography of the biceps tendon.

The purpose of this study was to analyse the factors having an influence on the arthrographic imaging of the biceps tendon. The study comprised 174 patients suffering from chronic shoulder pain. They underwent conventional shoulder arthrography with sodium meglumine metrizoate or metrizamide as a contrast medium. In the patients with a full-thickness tear of the rotator cuff, the biceps tendon sheath failed to fill with contrast medium more often than in those with an intact tendinous cuff. Metrizamide filled the biceps tendon sheath more readily than sodium meglumine metrizoate in patients with a full-thickness tear of the rotator cuff. The volume of the contrast medium injected had no influence on the imaging of the biceps tendon.

Glomerular filtration rate estimated from a single plasma sample after contrast-enhanced radiological examinations.

In twenty-six patients examined with radiographic procedures, including a single injection of meglumine metrizoate, blood samples were drawn 180, 200, 220 and 240 min after injection. Plasma was analysed for iodine concentration with X-ray fluorescence analysis and the total plasma clearance of metrizoate was calculated with the single sample method from each sample. The results were compared with the total plasma clearance of 51Cr-EDTA, calculated from multiple samples and determined no more than a few days apart from the X-ray examination. A good correlation, ranging from 0.91 and 0.94, was found. We therefore conclude that kidney function can be estimated from a single plasma sample after contrast-enhanced radiological examinations.

Complications in cerebral angiography with iohexol (Omnipaque) and meglumine metrizoate (Isopaque cerebral).

The complications of cerebral angiography have been recorded in 1509 examinations with metrizoate (Isopaque Cerebral) and in 1000 examinations with iohexol (Omnipaque). The frequency of complications was 2.0 percent for metrizoate and 1.3 percent for iohexol. Permanent sequelae were seen in 4 patients, 3 in the metrizoate and one in the iohexol group. One of these patients died, probably from thromboembolism. Blood coagulation parameters were studied during the angiography in 22 patients and only minor, probably clinically insignificant changes were found, with no difference between the two contrast media.

Renal function measured by x-ray fluorescence analysis. A comparison between contrast medium clearance and non-simultaneous 51Cr-EDTA clearance.

In twenty-six patients injected with metrizoate during urography, plasma was analyzed for iodine concentration using x-ray fluorescence analysis, and total plasma clearance of contrast medium was calculated. Total plasma clearance of 51Cr-EDTA was also determined, but not simultaneously, in order to find out if the urographic procedure would influence the kidneys to such an extent that the contrast medium clearance value would differ much from the 51Cr-EDTA clearance value. The errors in the method were assessed and the total error of the contrast medium clearance determination was calculated. When comparing 51Cr-EDTA and metrizoate clearance a correlation of 0.94 and a mean ratio of 1.046 (SD 0.138) was found. The assessable errors cannot fully explain the standard deviation, which might indicate a transient change in kidney function related to elements of the urographic procedure such as laxation with possible dehydration and/or the contrast medium dose.

Estimating kidney function during urography. Comparison of contrast medium clearance and simultaneous 51Cr-EDTA clearance.

Blood samples were taken from 21 subjects at 2 to 4 hours after simultaneous injection of contrast medium (metrizoate) for urography and 51Cr-EDTA. Clearance calculations were performed using the single injection (single slope) technique. The plasma concentrations of 51Cr-EDTA and contrast medium were measured by gamma counting and X-ray fluorescence analysis, respectively. A good correlation was found between the clearance of 51Cr-EDTA and clearance of contrast medium (r = 0.94).

Cytostatic effects of radiographic contrast media in synchronized cell cultures.

The cytostatic effects of conventional high osmolal ionic contrast media (meglumine-calcium metrizoate and Na-metrizoate) and new low osmolal nonionic contrast media (iohexol and iopamidol) in synchronized cell cultures were tested. The cell-cycle prolongation was most pronounced when the contrast media were added in the G1 phase, but there was also a marked effect when the contrast media were added in the S phase or late in the G2 phase. The cytostatic effect even persisted into the first cell cycle following the termination of the exposure. All four contrast media exerted effects stronger than that of equiosmolal saline. Iohexol and iopamidol produced a more severe effect than meglumine-calcium metrizoate and Nametrizoate at equal osmolality. Thus, the cytostatic effect of contrast media cannot be explained only by hypertonicity; the contrast media must have an additional specific cytostatic effect. When the cytostatic effect was related to iodine concentration, the new low osmolal nonionic contrast media influenced the cell cycle less than the conventional high osmolal ionic contrast media.