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PubMed1989

Experimental urography in dogs: diagnostic quality and pharmacokinetic behavior of iotrolan in comparison to nonionic and ionic, monomeric contrast media.

A dose of 0.3 g I/kg iotrolan yields much better opacification of the renal parenchyma in dogs (n = 6, intraindividual comparison) than sodium diatrizoate or iopromide, and imaging of the urinary tract is practically equally as good. The plasma iodine levels of all three agents 2 minutes after the bolus injections are 3 mg/ml and the half-lives in the blood are 8 to 10 minutes. The injection of iotrolan causes the hematocrit value to drop by maximum 3.8% 10 minutes after the injection, and corresponding figure after iopromide is 10.8% and that for sodium diatrizoate at 4 minutes is 18.9%. In a further study in dogs (n = 4, intraindividual comparison; dose 0.6 g I/kg) it was found that in the period 10 to 240 minutes after a bolus injection of iotrolan or iopamidol the iodine concentration in the urine was 1.5 to 2 times higher after iotrolan than after iopamidol. Iopamidol causes much higher urinary flow than iotrolan, especially in the first 20 minutes after injection. The properties of iotrolan described here appear to indicate that this novel nonionic, dimeric contrast medium has certain advantages over the monomeric, ionic and nonionic agents for urographic indications.

Animals↗
PubMed1989

Renal and hepatic tolerance of nonionic and ionic contrast media in intravenous digital subtraction angiography.

The liver and kidney tolerance of iopromide 370 in comparison to that of sodium meglumine diatrizoate 370 or iopamidol 370 in doses of 2 ml/kg body weight was examined in two controlled double-blind studies with intravenous digital subtraction angiography on the basis of enzyme assays in serum and urine. In patients with normal kidney function no changes were observed in the levels of the liver enzymes GPT, GOT, and gamma glutamyl transpeptidase (GGT) serum up to 72 hours after injection of iopromide or sodium meglumine diatrizoate. Among the kidney-specific enzymes, the excretion of GGT in urine increased after injection of iopromide and iopamidol. The maximum increase of GGT excretion was, however, statistically significantly lower in the group treated with iopromide than in the iopamidol group. Within 72 hours, the activities had been returned to the initial values in both groups.

Angiography↗
PubMedDate not supplied

Effect of contrast media on left ventricular function during left coronary arteriography in dogs.

The effect of contrast media on the left ventricular function of the heart was assessed by left coronary administration of contrast media using canine models. Following insertion of the catheter into the left coronary artery, 0.5 ml/kg of a test solution was injected at a rate of 1 ml/s. The test solutions included isotonic saline, meglumine/sodium diatrizoate, iopamidol and ioxaglate. The mean systemic pressure, left ventricular end-systolic and end-diastolic pressures and the first derivative of left ventricular pressure were continuously measured until five min post-injection. Left ventricular function decreased immediately by 15 s post-injection and recovered quickly by one min. The inhibition of myocardial contractility was observed with diatrizoate and ioxaglate to the same degree. These changes were statistically more pronounced than those with iopamidol, which showed changes similar to those with saline in all parameters except for the positive inotropic effects. These observations suggest that not only hyperosmolality but also ionic composition and chemotoxicity are the factors responsible for the myocardial depression and that no single factor dominates in their effects.

Animals↗
PubMedDate not supplied

Comparison of image quality and portal vein visualization in IADSP using iopamidol, 76% urografin, and 38% urografin.

The image quality of intra-arterial digital subtraction portography (IADSP) was studied in 50 randomly assigned patients using one of three contrast agents: iopamidol, (IOP, 20 cases), 76% Na-meglumine diatrizoate (76% UG, 20 cases), and 38% Na-meglumine diatrizoate (38% UG, 10 cases). Sharpness and contrast of images, and portal vein visualization were evaluated in these groups. IOP provided better image quality and portal vein visualization than 76% UG. There was no significant difference between them in terms of side effects, such as contrast medium-induced pain and feeling of warmth, or changes in physiological parameters like blood pressure and heart rate. When a low osmolar contrast agent like IOP passes through the mesentery capillary bed, the eflux of the contrast agent into the interstitial space and the influx of water into the capillary may be less, resulting in less dilution of the contrast agent in the superior mesenteric vein. This might explain the better image quality and portal vein visualization of IOP.

Diatrizoate Meglumine↗
PubMed1988

Cardiovascular responses following the intracarotid injections of ionic and nonionic contrast media compared with various mannitol solutions. Correlation with osmolality.

We injected iopamidol, meglumine diatrizoate, saline, and various mannitol solutions (5, 10, 20 weight/weight) into the right common carotid artery of anesthetized rabbits. To determine the cardiovascular responses to these injections, we measured and analyzed the changes in mean aortic pressure, mean carotid blood flow and its duration, volume of carotid blood flow, and resistance of carotid vascular bed. The volume change of carotid blood flow was calculated by the integration of blood flow. Mean aortic pressure decreased transiently and then returned to control levels within 10-20 seconds from the beginning of the injection for all agents. Carotid blood flow increased and carotid vascular bed resistance decreased transiently, returning to control levels within 10-20 seconds after the injection; the duration was found to be influenced by the agent's osmolality. Therefore, volume change was analyzed because it is a concurrent index of flow and duration. The cardiovascular response to each test agent was proportional to the agent's osmolality. Pearson's correlation coefficient was the highest between the volume change (increase) of carotid blood flow and the agent's osmolality (r = .8091). Increased volume of carotid blood flow appears to be a useful index for estimating the vasodilatory effects of contrast media. Iopamidol caused less severe cardiovascular responses than meglumine diatrizoate in experimental common carotid angiography; however, the responses were greater than for saline.

Animals↗
PubMed1985

Pharmacological action of radiographic contrast media reduced cerebrospinal fluid production in the dog.

Intravenous administration of radiographic contrast media (CM) significantly decreases cerebrospinal fluid (CSF) production as measured by negative pressure collection from a lateral ventricle of the anesthetized dog. This effect has been shown with the conventional ionic CM, sodium diatrizoate, and is now reported for the new nonionic agent, iohexol. Continuous infusion of either agent maintains the decrease. The magnitude of the CM-induced decreased CSF production is proportional to the dose in the range of 1 to 4 ml/kg. This action of CM cannot be explained by an osmotic mechanism. Two enzymes involved in the elaboration of CSF, carbonic anhydrase and sodium, potassium-adenosine triphosphatase, are not inhibited by sodium diatrizoate sufficiently in vitro to explain this action of CM. These results indicate a pharmacological action by i.v. CM that may require special attention when reduced CSF production would be deleterious.

Adenosine Triphosphatases↗
PubMedDate not supplied

Water-soluble contrast media compared with barium in enteric follow-through. Local effects and radiographic efficacy in rats with simple obstruction of the small bowel.

The local effects and radiographic efficacy of 4 water-soluble contrast media, barium and saline were evaluated in 86 anaesthetized rats with the distal ileum ligated. The rats were observed for 8 hours after instillation of 3 ml of the test substance via orogastric tube. Radiographs were taken after 1, 4 and 8 hours of observation. After 8 hours the intestines were weighed and biopsied for light microscopy, and blood and urine were sampled for testing. Sodium diatrizoate caused increased fluid influx to the bowel lumen and, like barium, provided poorer radiographic images as compared with iohexol, ioxaglate or iodixanol. Barium showed slower progression through the small bowel than the other agents, while sodium diatrizoate was the most rapidly progressing contrast medium and caused the greatest distension. Correlation to osmolality was obvious. No significant morphologic effects on the small bowel mucosa were seen in any of the groups. Low-osmolar, water-soluble contrast media may have prospects for clinical use in patients with suspected small bowel obstruction.

Animals↗
PubMed1987

A new density gradient for the separation of large quantities of rosette-positive and rosette-negative cells.

Allogeneic transplantation of peripheral blood stem cells will not be feasible until new techniques are developed for large-scale depletion of T-lymphocytes. Small quantities of cells can be depleted of T-lymphocytes by sheep erythrocyte rosetting and Ficoll-diatrizoate discontinuous gradient fractionation. However, when processing 10(9)-10(10) cells, the fractionation step is inefficient because of the limited capacity of Ficoll-diatrizoate. We therefore developed a new discontinuous gradient for the separation of large numbers of sheep red blood cell (RBC) rosette-positive and negative cells. The gradient was designed so that sheep cells and rosettes would not interfere with the banding of rosette-negative cells. In that way, nonspecific entrapment was reduced, and high cell capacity and yield were achieved. The system fractionated rosetted cell suspensions into four populations: free sheep RBC, rosetted T cells, nonrosetted T cells, and low-density non-T cells. The 15-ml gradient routinely separated 3-24 X 10(8) cells. Progenitor yield ranged from 83% to 99%, with 95% depletion of T-lymphocytes. The method is rapid, reproducible, and inexpensive. This preparative technique could prove useful clinically when large-scale separation of E-rosette-positive and negative cells is required.

Cell Separation↗
PubMed1980

Proteinuria following nephroangiography. VII. Comparison between ionic monomeric, monoacidic dimeric and non-ionic contrast media in the dog.

The degrees of albuminuria induced by nephroangiography in dogs with the ionic monomeric contrast medium diatrizoate, the non-ionic iopamidol, iohexol and C29 and the monoacidic dimeric contrast medium ioxaglate were compared. Diatrizoate induced significantly higher albuminuria than the other contrast media. No significant differences in the degree of albuminuria following angiography were found between iopamidol, iohexol, C29 and ioxaglate.

Albuminuria↗
PubMedDate not supplied

Neuroangiography with iohexol.

Iohexol is a new, nonionic water-soluble contrast agent undergoing early clinical trials in the United States. Using a double-blind, parallel format, iohexol was compared with meglumine iothalamate (60 patients) for selective cerebral angiography, and with sodium meglumine diatrizoate (40 patients) for arch aortography. Iohexol produced significantly less pain than meglumine iothalamate or sodium meglumine diatrizoate. There were no significant differences in terms of heart rate, blood pressure, or electrocardiogram (ECG) changes. Both produced a transient tachycardia and hypotension after arch aortography, but significantly less so with iohexol. No significant complications occurred. Film quality was comparable between contrast agents except for diminished motion artifacts with iohexol. Iohexol appears to be a superior neuroangiographic contrast agent to current ionic drugs.

Adult↗
PubMed1993

[The preventive effect of calcium-channel blockers (nifedipine, verapamil) on the tubular toxicity of radiographic contrast media (Verografin, Hexabrix)].

The authors investigated the nephrotoxic effect of the high-osmolar X-ray contrast medium (diatrizoate) and low-osmolar contrast medium (ioxaglate) and attempted to influence it by Ca channel blockers (nifedipine and verapamil). The criterium of tubular toxicity was the monitoring of urine wastes of tubular enzymes--alkaline phosphatase (ALP), gamma glutamyl transferase (GMT) and N-acetyl-beta-D-glucosaminidase (NAG). As criterium of glomerular functions he authors assessed the endogenous creatinine clearance. The experiments were made on outbred male rats Wistar strain for a total of 7 days following administration of the contrast medium. In animals to whom contrast medium only was administered a significant increase of urine waste of the investigated enzymes was observed. Maximum changes were recorded in the excretion of brushborder enzymes. Diatrizoate caused a significantly higher increase of enzymuria than ioxaglate. Administration of Ca channel blockers significantly reduced this rise of enzymuria, but the authors were unable to eliminate this rise completely. There were no statistically significant differences between the action of nifedipine and verapamil.

Acetylglucosaminidase↗
PubMed1994

[Electrocardiographic and hemodynamic adverse effects of contrast media in coronary angiography].

In a randomized double-blind study in 50 patients (38 men, 12 women of medium age 52.2 +/- 8 years) the new non-ionic low-osmolal x-ray contrast agent Iomeprol 400 is compared with the high-osmolal contrast medium natrium-meglumine-diatrizoate (Urografin 76). Electrocardiographic, hemodynamic as well as general effects and side-effects such as bradycardias, tachyarrhythmias, allergic reactions, attacks of hyperhidrosis, nausea, vertigo, thoracal pain, cephalgies after selective coronary angiography and levocardiography were registered. Between the two groups of patients there were no major differences concerning age, sex, weight, and coronary status. After coronary angiography in the two groups the following parameters were statistically significant: Iomeprol 400 led to a smaller reaction of heart rate (P = 0.001 during left coronary injection or P = 0.003 during right coronary injection), to a lower rise of the QT-time (P = 0.0005 for right coronary injection or P = 0.0001 for left coronary injection) as well as to a mild change of the T-vector (P = 0.0002 in right coronary injection or P = 0.0001 in left coronary injection). After levocardiography using natrium-meglumine-diatrizoate versus Iomeprol 400 a significantly stronger decrease in systolic (P = 0.0001) and diastolic (P = 0.0001) aortic pressure was registered. The increase of heart rate was less frequent with Iomeprol 400 than using the ionic contrast medium, which was compared to it (P = 0.048). In the general effects with Iomeprol 400 a statistically significantly less frequent appearance of bradycardias was registered (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Contrast media-induced renal morphologic lesions in diabetic rats.

Diabetes mellitus was induced in rats with streptozotocin and after 3 months the animals (n = 48) received an i.v. injection of 1 or 3 g I/kg in the form of high-osmolar diatrizoate, low-osmolar iopromide or iohexol, or of 0.6 g I/kg of high-osmolar Gd-DTPA. The controls were given an i.v. injection of physiologic saline. After 2 hours the kidneys were fixed by perfusion and the renal morphologic changes were semiquantitatively analyzed by two independent observers unaware of the agent administered. The contrast media (CM) induced pronounced cytoplasmic vacuolization in the proximal convoluted tubular cells. Such a lysosomal alteration may indicate CM uptake into the cell, and the ultrastructural evaluation revealed intracellular injuries related to the process. The alterations were most marked following administration of iohexol, but diatrizoate also induced a statistically highly significant vacuolization (p < 0.001). The lysosomal alterations following iopromide administration were not as striking, and Gd-DTPA induced only minor changes.

Animals↗
PubMed1998

Effects of radiographic contrast agents on thrombin formation and activity.

Clinical trials suggest that the risk of thrombosis during coronary angioplasty is lower with ionic contrast agents than with nonionic contrast agents. However, the molecular mechanisms underlying this effect are unknown. This study examined the effects of contrast agents on thrombin formation and its interaction with substrates, inhibitors, and ligands to define potential mechanisms by which contrast agents affect thrombus formation. Two ionic agents, diatrizoate and ioxaglate, and one nonionic agent, ioversol, were studied. Ionic agents inhibited factor X activation by the tissue factor-factor VIIa complex more potently than ioversol (53 +/- 3.7, 43.0 +/- 1.9, and 26.5 +/- 2.4% inhibition by diatrizoate, ioxaglate, and ioversol, respectively, at concentrations of 5%). Ionic contrast agents were potent inhibitors of prothrombinase function, inhibiting thrombin formation by >75% at contrast concentrations of 0.6% (p <0.005). Ioversol inhibited prothrombinase to a significantly lesser extent than ionic agents. Clotting assays suggested that ioxaglate was the most potent inhibitor of thrombin generation in plasma despite having the least effect on fibrin polymerization. Contrast agents inhibited binding of thrombin to fibrin, with ionic agents producing a more potent effect than ioversol (p <0.02). However, contrast agents did not inhibit thrombin-mediated platelet activation, had only a minor effect on inhibition of thrombin by antithrombin III, and did not affect thrombin-hirudin interactions. In summary, these studies identify specific mechanisms by which radiographic contrast agents inhibit thrombin formation and function -- i.e. inhibition of tissue factor-dependent factor Xa generation, inhibition of the prothrombinase complex, and inhibition of thrombin binding to fibrin. These findings may help to explain the reduced risk of thrombosis during coronary angioplasty associated with ionic contrast agents.

Cardiac Catheterization↗
PubMed1992

Use of ultrasound imaging and fluoroscopic imaging to study gastric retention of enzyme-digestible hydrogels.

Ultrasound and fluoroscopic imaging techniques were used to monitor the gastric retention of enzyme-digestible hydrogels in the canine stomach. When water was present in the stomach, ultrasound imaging was very effective in monitoring the position of the hydrogel in the stomach, solvent penetration into the gel, and the gastric tissue-gel interactions during peristalsis. Rubbery or fully swollen hydrogels appeared as sonolucent objects with ultrasound imaging. Partially swollen hydrogels displayed a sonolucent outer layer due to solvent penetration and a centrally located bright echo resulting from the acoustic impedance mismatch at the glassy/rubbery interface. The degree of gastric tissue-gel interactions during peristalsis was inversely related to the extent of lumenal distention with water. The effectiveness of peristaltic contractions in driving the hydrogel toward the pyloric sphincter increased as the water was emptied from the stomach. In the absence of water, imaging of the gel with ultrasound became difficult. For this reason, gels were loaded with diatrizoate meglumine/sodium diatrizoate to visualize in real-time using fluoroscopic imaging. Fluoroscopic imaging allowed only indirect assessment of the hydrogel movement during peristalsis and the degree of hydrogel swelling. The gastric retention of the hydrogel under fasted conditions was influenced by the degree of gel deformation in response to peristaltic contractions. Hydrogels with a low degree of deformation during peristalsis showed long gastric retention times. The utilization of ultrasound imaging and fluoroscopic imaging for monitoring dynamic events in the stomach provided information on hydrogel properties which are important to gastric retention. The use of these imaging techniques in the development of long-term oral drug delivery systems is described.

Administration, Oral↗
PubMed1991

Large-scale purification of inactivated hepatitis A virus by centrifugation in non-ionic gradients.

Formalin-inactivated hepatitis A virus (HAV) can be purified for vaccine preparation by centrifugation in Renografin-76 (diatrizoate meglumine and diatrizoate sodium) gradients. Both continuous-flow rate-zonal and isopycnic methods were used for the separation of a major antigen component from minor antigen and host protein. The major antigen component, which appeared to contain complete virions by electron microscopy, could be recovered from gradients and accounted for approximately one third of the total antigen in the starting material. The HAV-specific purified antigen could be enriched 200-300-fold by either centrifugation procedure. The purified HAV antigen, when adsorbed to alum and inoculated into mice, was found to be highly immunogenic.

Antigens, Viral↗
PubMed1989

Myocardial perfusion imaging by contrast echocardiography with use of intracoronary sonicated albumin in humans.

Sonicated albumin has been proposed as a near ideal echocardiographic contrast agent with little myocardial toxicity or hemodynamic effect. Its use has not yet been reported in humans, partly because of difficulties in preparation. With use of the newly modified sonication method, 10 ml of 5% albumin was sonicated for 75 s with a 5.0 ml slow infusion of air. This resulted in microbubbles with a mean diameter (+/- SD) of 5 +/- microns). Fourteen patients undergoing routine coronary angiography were studied. One patient had normal coronary arteries; the other 13 had significant coronary artery disease. In a subgroup of nine patients, sonicated albumin and sonicated diatrizoate meglumine sodium (microbubble diameter 9 +/- 3 microns) were injected several minutes apart, using the same technique. Videodensity-time curves were obtained from a region of interest in the myocardium. Corrected peak contrast intensity (baseline contrast intensity subtracted from peak contrast intensity, gray scale U/pixel) for sonicated albumin and for sonicated diatrizoate meglumine sodium was 51 +/- 26 and 52 +/- 19, respectively (p = 0.89). Washout half-time (T1/2) for the two agents was 5.5 +/- 4.5 and 16.0 +/- 12.2 s, respectively (p = 0.01). One patient with unstable angina experienced transient chest pain after repeated albumin injections. No electrocardiographic changes, blood pressure changes or wall motion abnormalities were observed. Administered by intracoronary injection, sonicated 5% albumin is a safe and effective echocardiographic contrast agent for myocardial perfusion imaging, yielding excellent myocardial contrast with physiologic washout time.

Adult↗
PubMed2006

Radiocontrast media cause dephosphorylation of Akt and downstream signaling targets in human renal proximal tubular cells.

Radiocontrast medium induced nephrotoxicity is a major clinical problem. There is considerable interest in reducing the incidence of acute renal failure due to the use of radiocontrast media (RCM). Reduction of renal blood flow and direct toxic effect on renal tubular epithelial cells have been postulated as major causes of RCM nephropathy. Understanding the molecular mechanisms by which RCM cause cell damage may allow the development of pharmacological therapy to prevent their nephrotoxicity. In this work we have investigated the signaling pathways that may be affected by RCM. The incubation of human renal tubular proximal cells with sodium diatrizoate, iopromide and iomeprol caused a marked dephosphorylation of the kinase Akt on Ser473 within 5min of incubation. RCM also caused a decrease in cell viability, which was substantially alleviated by transfecting the cells with a constitutively active form of Akt. Further downstream targets of Akt, including the Forkhead family of transcription factors FKHR and FKHRL1, were also dephosphorylated by RCM at Thr24 and Thr32, respectively. The P70S6 kinase was also dephosphorylated at Thr389 and Ser371 by RCM. However there was a more dramatic decrease in phosphorylation of the phosphorylated form of mammalian target of rapamycin (mTOR) and of the extracellular-signal regulated kinases (ERK) 1/2 caused by sodium diatrizoate than by iopromide. These results demonstrate the effect of RCM on some intracellular signaling pathways that may allow understanding of the mechanism of their toxicity and may allow the development of strategies to overcome their adverse effects.

Cell Line↗