Murine articular cartilage morphology and compositional quantification with high resolution cationic contrast-enhanced µCT.

Articular cartilage lines the load-bearing surfaces of long bones and undergoes compositional and structural degeneration during osteoarthritis progression. Contrast enhanced microcomputed tomography (µCT) is being applied to a variety of preclinical models, including the mouse, to map structural and compositional properties in 3-D. The thinness (∼30-50 µm) and high cellularity of mouse articular cartilage presents a significant imaging challenge. Our group previously showed that mouse articular cartilage and proteoglycan (PG) content can be assessed by µCT with the ioxagalate-based contrast agent Hexabrix, but the voxel size used (6 µm) was deemed to be barely adequate. The objective of the present study is to assess the utility of a novel contrast agent, CA4+, to quantify mouse articular cartilage morphology and composition with high resolution µCT imaging (3 µm voxels) and to compare the sensitivity of CA4+ and Hexabrix to detect between-group differences. While both contrast agents are iodine-based, Hexabrix is anionic and CA4+ is cationic so they interact differently with negatively charged PGs. With CA4+, a strong correlation was found between non-calcified articular cartilage thickness measurements made with histology and µCT (R2 = 0.72, p < 0.001). Cartilage degeneration-as assessed by loss in volume, thickness, and PG content-was observed in 34-week-old mice when compared to both 7- and 12-week-old mice. High measurement precision was observed with CA4+, with the coefficient of variation after repositioning and re-imaging samples equaling 2.8%, 4.5%, 7.4% and 5.9% for attenuation, thickness, volume, and PG content, respectively. Use of CA4+ allowed increased sensitivity for assessing PG content compared to Hexabrix, but had no advantage for measurement of cartilage thickness or volume. This improvement in imaging should prove useful in preclinical studies of cartilage degeneration and regeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2740-2748, 2017.

Incompatibility of contrast medium and trisodium citrate.

PURPOSE: To test the compatibility of trisodium citrate, a catheter lock solution, with iodinated contrast medium. METHODS: Iohexol, iobitridol, iodixanol, ioxaglate, ioxithalamate, iomeprol, and iopromide were tested. In all tests, 2 ml of contrast medium were mixed with 2 ml of trisodium citrate solution. RESULTS: Iodixanol and ioxaglate provoked a highly viscous gluelike precipitation when mixed with trisodium citrate. A brief transient precipitate was observed with iohexol, iomeprol, and ioxithalamate. Permanent precipitation occurred with iobitridol and iopromide. CONCLUSION: One must be aware of the potential for precipitation when contrast medium is mixed with trisodium citrate solution. Before trisodium citrate solution is injected, the catheter should be thoroughly flushed with saline if a contrast medium has previously been injected through it.

Contrast-enhanced CT with a high-affinity cationic contrast agent for imaging ex vivo bovine, intact ex vivo rabbit, and in vivo rabbit cartilage.

PURPOSE: To quantify the affinity of a cationic computed tomography (CT) contrast agent (CA(4+)) and that of an anionic contrast agent (ioxaglate) to glycosaminoglycans (GAGs) in ex vivo cartilage tissue explants and to characterize the in vivo diffusion kinetics of CA(4+) and ioxaglate in a rabbit model. MATERIALS AND METHODS: All in vivo procedures were approved by the institutional animal care and use committee. The affinities of ioxaglate and CA(4+) to GAGs in cartilage (six bovine osteochondral plugs) were quantified by means of a modified binding assay using micro-CT after plug equilibration in serial dilutions of each agent. The contrast agents were administered intraarticularly to the knee joints of five New Zealand white rabbits to determine the in vivo diffusion kinetics and cartilage tissue imaging capabilities. Kinetics of diffusion into the femoral groove cartilage and relative contrast agent uptake into bovine plugs were characterized by means of nonlinear mixed-effects models. Diffusion time constants (τ) were compared by using a Student t test. RESULTS: The uptake of CA(4+) in cartilage was consistently over 100% of the reservoir concentration, whereas it was only 59% for ioxaglate. In vivo, the contrast material-enhanced cartilage reached a steady CT attenuation for both CA(4+) and ioxaglate, with τ values of 13.8 and 6.5 minutes, respectively (P = .04). The cartilage was easily distinguishable from the surrounding tissues for CA(4+) (12 mg of iodine per milliliter); comparatively, the anionic contrast agent provided less favorable imaging results, even when a higher concentration was used (80 mg of iodine per milliliter). CONCLUSION: The affinity of the cationic contrast agent CA(4+) to GAGs enables high-quality imaging and segmentation of ex vivo bovine and rabbit cartilage, as well as in vivo rabbit cartilage. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112246/-/DC1.

Comparison of the usefulness of gadodiamide and iodine mixture versus iodinated contrast alone for prevention of contrast-induced nephropathy in patients with chronic kidney disease undergoing coronary angiography.

Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired renal failure. Gadolinium-based contrast agents have been proposed as alternatives to iodinated contrast in patients at high risk for CIN. The use of high-dose intraarterial gadolinium chelates in the catheterization laboratory has been investigated in only a small number of patients. We compared patients with a creatinine clearance <60 ml/min/1.73 m2 who received intravenous hydration (> or =1,500 ml) and oral n-acetylcysteine prophylaxis with those who received a gadodiamide-iodine mixture (n = 90) or iodinated contrast alone (n = 79) in the cardiac catheterization laboratory. CIN was defined as an increase of 0.5 mg/dl in serum creatine from baseline. The 2 groups were similar with respect to demographics and risk factors. Although less iodinated contrast was used in the gadolinium mixture group, there was no difference in the incidence of CIN between the 2 groups. However, the initiation of dialysis (n = 7) and death (n = 8) only occurred in the diluted gadolinium contrast group. A stepdown multivariate analysis found diabetes mellitus to be the only independent predictor of CIN (p = 0.02, odds ratio 3.35, 95% confidence interval 1.21 to 9.29, c-statistic 0.66). In conclusion, the incidence of CIN was not decreased in high-risk patients receiving a gadolinium-iodinated contrast mixture versus iodinated contrast alone.

Renal toxicity evaluation and comparison between visipaque (iodixanol) and hexabrix (ioxaglate) in patients with renal insufficiency undergoing coronary angiography: the RECOVER study: a randomized controlled trial.

OBJECTIVES: This study sought to compare the nephrotoxicity of iodixanol and ioxaglate in patients with renal impairment undergoing coronary angiography. BACKGROUND: Iodixanol, a nonionic, dimeric, iso-osmolar contrast medium (IOCM), may be less nephrotoxic than low-osmolar contrast media (LOCM) in high-risk patients. METHODS: In a prospective, randomized trial in 300 adults with creatinine clearance (CrCl) < or =60 ml/min, patients received either iodixanol or ioxaglate and underwent coronary angiography with or without percutaneous coronary intervention. The primary end point was the incidence of contrast-induced nephropathy (CIN) (an increase in serum creatinine [SCr] > or =25% or > or =0.5 mg/dl [> or =44.2 mumol/l]). The incidence of CIN in patients with severe renal impairment at baseline (CrCl <30 ml/min) or diabetes and in those receiving large doses (> or =140 ml) of contrast medium was also determined. RESULTS: The incidence of CIN was significantly lower with iodixanol (7.9%) than with ioxaglate (17.0%; p = 0.021), corresponding to an odds ratio (OR) of CIN of 0.415 (95% confidence interval [CI] 0.194 to 0.889) for iodixanol. The incidence of CIN was also significantly lower with iodixanol in patients with severe renal impairment (p = 0.023) or concomitant diabetes (p = 0.041), or in patients given > or =140 ml of contrast media (p = 0.038). Multivariate analysis identified use of ioxaglate (OR 2.65, 95% CI 1.11 to 6.33, p = 0.028), baseline SCr, mg/dl (OR 2.0, 95% CI 1.04 to 3.85, p = 0.038), and left ventricular ejection fraction, % (OR 0.97, 95% CI 0.94 to 0.99, p = 0.019) as independent risk factors for CIN. CONCLUSIONS: The IOCM iodixanol was significantly less nephrotoxic than ioxaglate, an ionic, dimeric LOCM. (The RECOVER Trial; http://clinicaltrials.gov; NCT00247325).

Serum pancreastatin levels predict response to hepatic artery chemoembolization and somatostatin analogue therapy in metastatic neuroendocrine tumors.

INTRODUCTION: Neuroendocrine tumors often metastasize to the liver and present with disabling hormonal symptoms. Hepatic artery chemoembolization (HACE) combined with somatostatin therapy, pre-embolization, peri-embolization and post-embolization, at doses to control symptoms, is an aggressive approach that can relieve hormonal symptoms with minimal morbidity and mortality. METHODS: Chemoembolization was performed using 30 mg of adriamycin, 50 mg of mitomycin, 12 ml of hexabrix, 10 ml of ethiodol, and 360-500-microm particles. Pancreastatin, a split product of chromogranin A, was measured pre-HACE and post-HACE in all patients. RESULTS: Forty-three chemoebolization procedures were performed in 34 symptomatic patients from December 1995 to August 1999. Seventeen patients had intestinal primaries (50%), seven had pancreatic primaries (20%), five had bronchial primaries (15%), and five had unknown primaries (15%). Systemic pancreastatin levels were improved or stable in 31 patients (78%). Symptoms were improved in these 31 patients (78%). Systemic serotonin levels were improved or stable in 24 patients (60%). Radiographic improvement or stability was seen in 18 patients (45%). Procedural related morbidity included pain, fevers, nausea, vomiting, and transient elevations of liver function studies in 75-100% of patients. There was one procedural related mortality (2%). Less than 20% improvement in pancreastatin levels from baseline was associated with death in five of five patients (100%). This was not observed with serotonin levels. CONCLUSION: Measurement of serum pancreastatin levels is an easy and useful method to predict success in patients who undergo HACE plus somatostatin therapy for metastatic neuroendocrine tumors to the liver. This therapeutic approach is effective in relieving symptoms in 78% of patients, with minimal major morbidity or mortality.

Feasibility of synchrotron radiation computed tomography on rats bearing glioma after iodine or gadolinium injection. Jeune Equipe RSRM-UJF.

The purpose of this work was to demonstrate the feasibility of a new imaging technique called synchrotron radiation computed tomography (SRCT). This technique leads to a direct assessment of the in vivo concentration of an iodine- or gadolinium-labeled compound. Rats bearing C6 glioma were imaged by MRI prior to the SRCT experiment. The SRCT experiments were performed after a 1.3 g I/kg (n = 5) or a 0.4 g Gd/kg (n = 5) injection. Finally, brains were sampled for histology. The SRCT images exhibited contrast enhancement at the tumor location. Ten minutes after injection, iodine and gadolinium tissular concentrations were equal to 0.80 ( +/- 0.40) mg/cm3 and 0.50 ( +/- 0.10) mg/cm3, respectively in the peripheral area of the tumor (respective background value: 0.20 +/- 0.02 to 0.10 +/- 0.01). Correlation to MRI and histology revealed that the contrast uptake occurred in the most vascularized area of the tumor. The present study summarizes the feasibility of in vivo SRCT to obtain quantitative information about iodine and gadolinium-labeled compounds. Beyond brain tumor pathology, the SRCT appears as a complementary approach to MRI and CT, for studying iodine- and gadolinium-labeled compounds by the direct achievement of the tissular concentration value in the tissue.

Contrast medium-induced pulmonary edema is aggravated by silicone contamination in rats.

PURPOSE: To examine the effect of silicone contamination, which occurs in clinical settings during vial preparation with disposable syringes, on contrast medium-induced pulmonary edema in rats. MATERIALS AND METHODS: Ioxaglate, ioversol, and iohexol, silicone-containing physiologic saline solutions, and three silicone-containing contrast media were separately, intravenously injected at 1.5 mL/min in rats. Pulmonary edema was evaluated as changes in the relative lung weight and in the water, sodium, and potassium contents of the lung. RESULTS: Intravenous injection of ioxaglate induced marked pulmonary edema, even with a dose of only 4 g of iodine per kilogram of body weight. In contrast, ioversol and iohexol induced significant pulmonary edema only after the injection of large doses (6 g of iodine per kilogram; P < .05). The injection of 4 microL/mL silicone-containing physiologic saline at a dose of 18.75 mL/kg also produced marked pulmonary edema, whereas doses of 6.25 and 12.5 mL/kg showed no significant influence. The addition of an ineffective dose (12.5 mL of physiologic saline per kilogram of body weight) of silicone in contrast medium substantially aggravated the pulmonary edema induced by the contrast medium alone; this phenomenon was also confirmed with morphologic observation. CONCLUSION: Ionic contrast media are more toxic to the endothelial cells than are nonionic contrast media. Silicone contamination might be one of the causes of pulmonary edema after intravenous injection. However, caution must be exercised in extrapolating these results to humans.

The effect of antihistamine, endothelin antagonist and corticosteroid prophylaxis on contrast media induced bronchospasm.

Bronchospasm is a well recognized adverse reaction to radiographic contrast media (RCM) and may occur more frequently in asthmatics and atopics. This study was designed to identify RCM which are most likely to cause bronchospasm and to investigate underlying mechanisms mediating this response. Guinea pigs (mean body weight 550 g, n = 46) were anaesthetized with Hypnorm (5 ml kg-1) and Hypnovel (2 ml kg-1) and tracheal, jugular and pleural cannulae introduced. Total airways resistance (Raw) was calculated from the slope of the pressure/flow relationship. The effects of RCM (diatrizoate 370 mgI ml-1, ioxaglate 320 mgI ml-1, iotrolan 300 mgI ml-1 and iopromide 300 mgI ml-1) at a dose of 4 ml kg-1 body weight or control solutions matched for volume, pH and osmolarity administered via the jugular vein on Raw were studied. The effects of pre-treatment (30 min before the administration of RCM) with antihistamine (Mepyramine (30 mg kg-1 i.p.)) or non-selective endothelin receptor antagonist (SB209670 (1 mg kg-1 i.v.)) were investigated. The effectiveness of corticosteroids prophylaxis (prednisolone (20 mg kg-1 i.p.)) administered 18-24 h and 1 h pre-RCM was also assessed. Control animals received normal saline pre-treatment before RCM administration. Lungs were taken for histological examination 30-40 min post-administration of RCM. Only ioxaglate caused a significant (p < 0.05) increase in Raw (5.19 +/- 0.58 to 13.95 +/- 3.53 mmHg ml-1 min-1). Neither mannitol nor saline control solutions had any effect on Raw. Pre-treatment with Mepyramine, SB209670 or prednisolone caused no significant change in the ioxaglate induced increase in Raw. Histological examination of lung tissue from ioxaglate treated animals showed no important abnormalities. In summary, only the ionic dimer ioxaglate caused an increase in Raw. This effect was independent of osmolarity and could be the result of the chemical composition of the contrast agent. It was not an inflammatory response and could not be prevented by prophylactic treatment with antihistamine, endothelin antagonist or corticosteroids. The mechanisms responsible for the increase in Raw remain uncertain.

Diagnosis of Hirschsprung's disease.

OBJECTIVE: Our aims were to determine the validity of using low-osmolality water-soluble contrast enemas (WSCE) in neonates and infants with suspected Hirschsprung's disease (HD) and to devise a scoring system that uses a checklist of radiologic signs to determine the probability of HD. MATERIALS AND METHODS: The records of all patients referred by pediatric surgeons from 1988 through 1992 for the radiologic investigation of possible HD were retrospectively reviewed. Thirty-eight patients who were from 2 days to 9 months old were studied; 20 of them were neonates (less than 1 month old). Of all the patients, 24 underwent WSCE and the other 14 underwent barium enema. For all patients, HD had been diagnosed by rectal biopsy or excluded by biopsy, clinical follow-up, or both. Radiographs were read by a gastrointestinal radiologist who used a checklist of diagnostic criteria reported in the literature. The sensitivity had specificity of the findings were compared with those in the literature. RESULTS: Of the 18 patients with HD, 12 were neonates. All reported radiologic diagnostic criteria were seen; the frequency, sensitivity, and specificity of the findings were reported. Twenty percent (n = 2) of HD patients in the WSCE group (n = 10) had negative findings. Two of the 12 neonates developed colonic perforation, one during the enema and the other within 24 hr of the procedure. CONCLUSION: WSCE has a sensitivity and specificity equivalent to those of the barium enema for the detection of HD. For the two patients with perforation, the use of WSCE was of considerable benefit, avoiding the problems associated with barium spillage into the peritoneal cavity. A scoring system for diagnostic enemas is feasible.

Electrolyte addition to nonionic contrast media. Cardiac effects during experimental coronary arteriography.

Although the incidence of serious adverse effects is low during clinical coronary arteriography, life-threatening cardiovascular complications occasionally occur. Ventricular fibrillation (VF) is most often seen during contrast media (CM) injection through a wedged catheter. A simulated wedged catheter model in dogs has therefore been developed. Further, patients with heart failure are at greater risk for CM-related side effects during coronary arteriography. Thus, an acute ischemic heart failure model has been used. The present thesis was designed to investigate the cardiac electrophysiologic and hemodynamic effects of CM during selective coronary arteriography in normal and failing hearts, and in particular the role of electrolyte addition to nonionic CM. The risk of spontaneously induced VF and the arrhythmogenic mechanisms were studied when using iso-osmolal and low-osmolal CM having different contents of electrolytes, and after pretreatment with antiarrhythmic drugs. Further, effects of adding electrolytes to nonionic CM during single and fast repeated injections in normal and failing hearts were studied. Also possible effects of oxygenating CM were studied. CM injection in a wedged catheter situation had a high risk for VF. Probably, VF was due to induced regional electrophysiologic changes in ventricular activation and repolarization. Pretreatment with antiarrhythmic drugs did not prevent VF. However, addition of low concentrations of electrolytes to nonionic CM reduced the risk for VF in a wedged catheter situation. The results indicate that side-effects of CM during coronary arteriography are related mainly to the passive washout of cardiac electrolytes. Electrolyte shifts during coronary arteriography may change the myocardial Na/Ca balance and cellular calcium control. The nonionic, iso-osmolal CM iodixanol, with a balanced content of sodium and calcium and the low-osmolal, nonionic CM iohexol, also with a balanced content of electrolytes, had about the same low risk for inducing VF and presented a much lower risk for inducing VF than did iohexol and ioxaglate in a wedged catheter situation. Single injection of iohexol with a balanced eletrolyte addition induced only minimal electro-physiologic changes and was well tolerated hemodynamically. Repeated intracoronary CM injections during ischemic heart failure were associated with similar additive electrophysiologic and hemodynamic changes as when using iohexol without electrolyte supplement. Oxygenated and nonoxygenated CM presented the same risk for inducing VF. Only minor electrophysiologic and hemodynamic differences could be detected during wedged catheter injection. In conclusion, addition of key electrolytes to nonionic CM can reduce the risk of cardiac complications during coronary arteriography. Oxygenation of CM does not seem to significantly further reduce the risk.

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.

A Study of Radiocontrast Media Induced Nephrotoxicity

PURPOSE: This study was aimed at determining whether tri-iodinated compounds with greater solubility and low osmolality, Na or meglumine ioxaglate(Hexabrix 320, Guerbet Lab., France) had deleterious effects on renal function after cardiac angiography for the evaluation of congenital heart disease(CHD) and determining whether correction of dehydration using iv hydration given before cardiac angiography were effective in prventing renal dysfunction. METHODS: For the study of radiocontrast media induced nephrotoxicity, 21 children with various CHDs admitted to the hospital for the evaluation of their CHDs. None of them had any evidence of renal dysfunction before study. They were devided into 2 groups, one was low-dose group(ioxaglate given, < 2.0 mL/kg) and the other one was high-dose group(>2.0 mL/kg). Renal function studies including serum creatinine(Scr), fractional excretion of sodium(FENa) and urinary beta2-microglobulin excreton(mg of beta2- microglobulin per gm creatinine) were done before and after ioxaglate administration. For the study of hydration effect on radiocontrast media induced nephrotoxicity, 9 children with CHDs were subjected. Thery were hydated with 5% D/S 1 hr before cardiac angiography using high-dose ioxaglate(> 2.0 mL/kg) and maintained on fluid therapy during the examination. Renal function studies were done before and after ioxaglate administration. Statistical analyses were done using Wilcoxon signed rank test. RESULTS: 1) Scr level and FENa were not increased significantly after administration of ioxaglate in both of low-dose and high-dose group. 2) A significant increase of urinary beta2M per creatinine excretion(mg/gm creatinine) was observed after administration of ioxaglate n the high-dose group(0.24 vs 0.57, p0.05) 3) Hydration before ioxaglate administration made urinary B2M per creatinine excretion insignificant even in patients who received high-dose ioxaglate, more than 3.0 ml/kg(0.22 vs 0.27, p>0.55). 4) Uric acid and/or calcium oxalate crystaluria appeared after ioxaglate administration, particularly in patients with dehydration. CONCLUSIONS: Ioxaglate, a low osmolality ionic dimer contrast media, could induce renal tubular dysfunction, which depended on dose used. Correction of dehydration before ioxaglate administration significantly reduced the risk of ioxaglate induced nephrotoxicity.

Current usage of contrast agents, anticoagulant and antiplatelet drugs in angiography and angioplasty in the UK.

Currently, there is no consensus in the UK on what constitutes best angiographic practice. To provide a basis for discussion a questionnaire was sent to all Radiology and Cardiology departments in the UK. Information was requested on practice during diagnostic angiography and angioplasty regarding the type of contrast agent used, whether and how flush solution or contrast agents themselves were heparinised, and whether bolus doses of heparin were administered. The use of other supplementary drugs including corticosteroids was also explored. Two hundred of 353 (57%) of questionnaires were returned. Over 80% who replied used non-ionic contrast agents for all angiographic procedures. The majority of the smaller group, using ionic contrast agents for uncomplicated procedures, resorted to non-ionic contrast agents in a range of circumstances in both diagnostic angiography and angioplasty. Heparinized flush solutions were used by over 75% for both types of angiographic procedures, but employing a wide range of doses. Bolus doses of heparin were administered by over 80% performing angioplasty, again in a wide range of doses, with only (a few) cardiologists monitoring the anticoagulant effect by measuring the activated whole blood clotting time in the angiographic suite. Over 70% used aspirin or dipyridamole as supplementary agents, at the time of the angioplasty and, subsequently, continued these medications for a variable period. Corticosteroid prophylaxis for high risk patients, very variably defined, was felt necessary by 58%. A wide range of regimes of both dose and timing was noted.

Cardiac hemodynamic effects of iodixanol, iopamidol, and ioxaglate following left coronary injections in anesthetized dogs.

RATIONALE AND OBJECTIVES: Iodixanol, a dimeric, nonionic X-ray contrast medium, has been formulated at 320 mg iodine per milliliter and supplemented with Na+, Ca2+, and Cl- to produce an osmolality that approximates that of plasma. We compared the effects of left main coronary artery injections of iodixanol, ioxaglate, and iopamidol on cardiac mechanical function in dogs. METHODS: Six mixed-breed dogs were anesthetized and prepared for recordings for electrocardiogram, aortic and left ventricular pressures, and the first derivative of left ventricular pressure, dP/dt. The test solutions and saline were injected into the left coronary artery in a randomized order. The series of four injections were repeated three times in each animal for a total of 12 injections per dog. RESULTS: Iodixanol caused significantly lower (p < .05) reduction in peak left ventricular pressure (-1.7 +/- 0.9% vs -0.7 +/- 2.0%), in diastolic aortic pressure (-1.3 +/- 1.1% vs -9 +/- 1.3%), and in left ventricular dP/dt (0.3 +/- 1.3% vs -13.2 +/- 2.4%) than did ioxaglate. Iodixanol also produced smaller cardiovascular effects than did iopamidol, but the differences were not statistically significant. Injections of both iopamidol and ioxaglate caused significant decreases from baseline parameter values; however, the changes with iodixanol were not significant. CONCLUSION: The isotonic formulation of iodixanol caused smaller cardiovascular hemodynamic effects than did iopamidol and ioxaglate and may offer increased safety in patients with severe cardiac disease.

An Experimental Study on Tissue Reaction of Various Contrast Agents on Endometrium, Tubal Mucosa, and Peritoneum

PURPOSE: To compare the tissue reactions of various water-soluble and oil-based contrast agents on the endometrium, salpingeat mucosa, and peritoneum. MATERIALS AND METHODS: Thirty-three rabbits were used for evaluating the histologic reactions of uterine endometrium, salpinx, and peritoneum. Hysterosalpingography(HSG) was underwent in these rabbits by using Lipiodol, Hexabrix, Rayvist, Ultravist-300, Ultravist-370, and normal saline. Pathotogic results were obtained in each of the six groups from the uterine endometrium, salpingeal mucosa, and peritoneum without knowledge of the contrast agent used and time interval from HSG. RESULTS: Mild inflammations were observed in the endometrium, salpingeal mucosa, and peritoneum during the first week of HSG in all rabbits in which water-soluble contrast agents were used. Although there was no significant difference in the degree of inflammation among the groups using various contrast agents, the group with oil-based contrast agent(Lipiodoi) showed delayed absorption of contrast agent in the peritoneum, frequent intravasation, fat granuloma, peritoneal adhesion, or uterine infarction. CONCLUSION: Our results suggest that water-soluble contrast agents can be used safely for HSG, but the use of oil-based contrast agent is questionable in safety and should be avoided in patients with tubal obstruction, salpingitis, or endometritis.

[Experimental histopathological studies of renal lesions induced by high- or low-osmolality contrast media].

To elucidate the morphological basis of renal lesions due to intravenous administration of radiocontrast media, a comparative study was performed by injecting contrast media with different properties, such as high-osmolar ionic diatrizoate (60% Urografin), low-osmolar ionic ioxaglate (Hexabix 320) and low-osmolar non-ionic iopamidol (lopamiron 300), via the tail vein of male Wistar rats. Physiologic saline was injected in controls. Each contrast media was administered singly as a low dose (1 g I/kg), a moderate dose (3 g I/kg) or a high dose (9 g I/kg) to three separate groups of rats. In additional groups of rats, a high dose of each contrast media (9 mg I/kg) was administered repeatedly two or four times. The animals were sacrificed chronologically from 5 minutes to 30 days after the last administration and their renal tissues were examined by light and electron microscopy. The results indicated that the low osmolar contrast media is beneficial in decreasing general symptoms, but there are no definite differences between high and low osmolar contrast media in the data of blood and urine examination after administration. The iodinated contrast media with a low or moderate dose does not induce definite histopathological changes of the renal tissue, however, with a high dose it causes vacuolization of proximal tubular epithelia, although this change recovers within three days. The repeated administration of contrast media with a high dose induces severe damage of proximal tubular epithelia with prominent vacuolization, appearance of intracytoplasmic granular structure and occasional cell necroses. The vacuolization appears even in distal and collective tubules and glomerular epithelia. Recovery is retarded under this condition. There are no qualitative histological differences of renal lesions induced by the three different contrast media. In conclusion, either high or low osmolar contrast media induces almost the same histological alteration in renal tissues under the same experimental conditions. The more the quantitative increase in administered iodinated contrast media, the more prominent is the histological impairment of the kidney. The degree of renal lesion and its recovery might depend on the dose of iodine rather than the osmolality of the contrast media.

The (in)compatibility of drugs and contrast media: a review of the literature.

This report presents a concise review of the available literature on the (in)compatibility of commonly used contrast media and equally well known drugs. The importance of avoiding injection of a medication that, when mixed with a contrast agent, does flocculate or precipitate is stressed.

[In vitro effects of ionic and non-ionic contrast media on erythrocyte aggregation]. / Effets in vitro de produits de contraste ionique et non ioniques sur l'agrégation érythrocytaire.

An in vitro model was designed to examine the effect of three contrast media (CM): two non ionic (Iohexol, Iopamidol) and one ionic (Ioxaglate) molecules on erythrocyte aggregation. Red blood cells were suspended in a chemically defined medium (Albumin: 10 g/l), Immunoglobulins: 12 g/l, Fibrinogen: 1.5 g/l) supplemented with various proportions of CM (10-25% V/V). Control samples contained NaCl or Saccharose solutions with a nearly similar osmolality. Erythrocyte aggregation at constant hematocrit (HT = 40%) was determined by the analysis of the light backscattered by blood suspension during the aggregation process. As compared to control samples, non ionic CM induced a weak decrease in erythrocyte aggregation, when the ionic molecule caused a marked increase in the aggregation, which was related to CM concentration. A different interaction of ionic and non ionic CM with erythrocyte membranes has been shown by fluorescence studies. After addition of CM, it was noted a fluorescence quenching of lipophilic probes (TMA-DPH and DPH) embedded in erythrocyte membranes. This quenching probably due to benzene ring and iodine atoms of contrast media markedly varied according to the used fluorescent probe and the CM. In the presence of ionic CM, the fluorescence quenching is more important than that induced by non ionic CM. Thus, besides osmolality and viscosity of CM which play a role in erythrocyte aggregation, some intrinsic properties of CM such as the ionic or non ionic nature could influence erythrocyte membrane-contrast medium interactions and consequently erythrocyte aggregation.