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PubMedDate not supplied

Modification of platelet aggregation and thromboxane synthesis by intravascular contrast media.

Radiographic contrast media (RCM) decreased significantly platelet aggregation in human platelet-rich plasma (PRP) after addition of arachidonic acid (AA) or adenosine diphosphate (ADP). Unlike hypertonic saline, diatrizoate, ioxaglate, and iopamidol (40 and 160 mM) inhibited AA-induced aggregation. One hundred sixty mM ioxaglate inhibited slightly the concomitant formation of immunoreactive thromboxane B2 (TXB2). The ionic RCM ioxaglate (40 and 160 mM) and diatrizoate (160 mM), but not the nonionic iopamidol, decreased the ADP-induced aggregation more than hypertonic saline. When PRP was incubated with different RCM without any aggregating agents or with ADP, the formation of TXB2 was negligible. Results of this study show that inhibition of AA- and ADP-induced platelet aggregation by RCM is partly due to hypertonicity and partly related to the chemical structure of the RCM molecule. The inhibition of AA-induced aggregation is not caused by the lack of formation of aggregatory TXA2.

Adenosine Diphosphate↗
PubMedDate not supplied

Comparative evaluation of the effects of an ionic vs. a nonionic contrast medium on the venous endothelium. Preliminary scanning electron microscopic observations.

Isolated segments of the right jugular veins of six mongrel dogs were exposed to solutions of 60% diatrizoate (3 dogs) and 60% iopamidol (3 dogs) in vivo. Normal blood flow was re-established after 3 minutes of exposure to the contrast material. The left jugular veins served as controls. Veins were harvested at 1, 24, and 48 hours and studied by light and scanning electron microscopy. Changes consisting of cellular swelling, denudation, platelet aggregation and fibrin deposition were uniform and prominent with diatrizoate. Response to iopamidol was minimal consisting only of cellular swelling. The study suggests that post-phlebographic thrombophlebitis may be reduced by the use of nonionic contrast materials.

Animals↗
PubMedDate not supplied

Cardiotolerance of iohexol. Survey of experimental evidence.

The risk of significant complications from contrast media is greatest in angiocardiography. Contrast media effects on central cardiovascular function include electrophysiologic effects such as bradycardia, hypotension, and ventricular arrhythmias; hemodynamic effects such as hypotension and blood flow changes; and metabolic effects such as transient hypocalcemia. Differences between ionic and nonionic media are less obvious in clinical studies but become apparent in carefully controlled animal experiments. Evidence indicates that nonionic media have less propensity to cause ventricular arrhythmias and bradycardia than ionic media. In addition, nonionic agents do not adversely affect left ventricular regional function and produced no negative inotropic effects in the presence of coronary stenosis. Unlike ionic diatrizoate, nonionic iohexol did not significantly interact with the calcium blocker, verapamil. Iohexol also produced no increase in lung water or in femoral blood flow, while diatrizoate produced increases in both. It is concluded that iohexol has fewer and less severe negative effects on central cardiovascular function than standard ionic media.

Angiocardiography↗
PubMed1987

Contrast enhancement of the liver. Evaluation by automated contiguous pixel search.

Eight dogs were infused with one of three different contrast agents: meglumine diatrizoate, iosulamide meglumine, or an ethiodized oil emulsion (EOE 13). Image intensity in the liver was evaluated globally and regionally by means of an automated pixel sampling method to determine differences in the rate of enhancement produced by the three agents. The results of the automated method were compared with those of the standard manual cursor method. The automated method showed that liver parenchyma was enhanced uniformly by all three contrast agents. The maximum degree of enhancement (Mean +/- SEM) for the three agents was diatrizoate, 12.0 +/- 3.5 Hounsfield units (HU); iosluamide, 21.3 +/- 3.5 HU; and EOE 13, 37.2 +/- 4.25 HU. With the manual cursor method, contrast enhancement was about 20% more than estimated by the automated method. The automated method is better for evaluating the magnitude and pattern of contrast agent enhancement of the entire liver, since the currently employed cursor technique requires multiple evaluations to evaluate the entire liver.

Animals↗
PubMed1987

Characterization of liposomes containing iodine-125-labeled radiographic contrast agents.

Multilamellar liposomes were prepared containing either iodine-125-labeled (125I) diatrizoate or 125-I labeled iotrol in their aqueous phase. The in vitro permeabilities of liposomes containing both contrast agents were measured in the presence of saline and serum at 37 degrees C. Two different phospholipid compositions were studied: phosphatidylcholine/cholesterol/stearylamine (PC/C/S, 8: 1:1 molar ratio) and distearoylphosphatidylcholine/sphingomyelin (DSPC/SM, 5:2 mole ratio). In saline, similar permeabilities were observed for the four phospholipid-contrast agent combinations. In serum, however, leakage of 125I activity was 2 to 3 times greater from PC/C/S liposomes than from vesicles composed of DSPC/SM. When PC/C/S liposomes that contained 125I-diatrizoate were injected into rats, the clearance half-times for 125I activity from the liver, spleen, and whole body were 4.4 hours, 4.5 hours, and 2.8 hours, respectively. Liposomes composed of DSPC/SM cleared at a significantly slower rate from the liver, spleen, and whole body with half-times of 24.0 hours, 18.4 hours, and 17.2 hours observed from these tissues, respectively.

Animals↗
PubMed1988

Effect of contrast media on prostaglandin synthesis in vivo.

Since systemic reactions to contrast media (CM) in patients often resemble pathophysiologic conditions associated with prostaglandin metabolites prostacyclin (PGI2), and thromboxane B2 (TXB2), plasma levels of these mediators are likely to provide an index of CM pathogenesis. In this study, patients undergoing peripheral arteriography were injected either with a hyperosmolal CM sodium diatrizoate or with a newer low osmolal CM, iohexol. Arterial blood samples were collected before and after the procedure. Prostacyclin and thromboxane were quantified as 6 ketoprostaglandin F1a (PGF1a) and TXB2 by using radioimmunoassay kits. Diatrizoate caused prostaglandin I2 (PGI2) release in 60% of patients, whereas 66% receiving iohexol also exhibited increased levels of PGI2 in their plasma. TXB2 concentration remained unchanged. No clinically adverse reactions were seen following the procedure. These results indicate that both high and low osmolality CM are capable of stimulating vascular endothelium, thereby causing prostacyclin release. Molecular mechanisms, however, remain to be determined.

Adult↗
PubMed1988

No pulmonary edema or congestion after central venous injection of conventional and newer contrast media in dogs.

Our aim was to determine whether large central venous doses of ionic diatrizoate, nonionic iopromide, or nonionic iotrolane produce pulmonary edema or pulmonary congestion in dogs. Eighteen dogs (six per group) anesthetized with piritramide and N2O received three sequential doses (1.5 mL/kg body weight) of one contrast medium in less than 20 seconds. Before the first injection, and again 1, 5, 10, 20, and 30 minutes after each contrast injection, extravascular lung water, pulmonary blood volume, and cardiac output were determined by thermal-dye dilution. Neither extravascular lung water nor pulmonary blood volume increased after any contrast medium. Pulmonary blood volume and cardiac output decreased slightly but not significantly after all contrast media during the course of the study. We conclude that diatrizoate, iopromide, or iotrolane do not produce pulmonary edema or congestion in dogs.

Animals↗
PubMed1988

Red blood cell aggregation versus blood clot formation in ionic and nonionic contrast media.

The effects of ionic and nonionic radiographic contrast media on human blood in plastic syringes were investigated in an in vitro double-blind study. Venous blood, which was drawn into plastic syringes containing one of four (iohexol, iopamidol, diatrizoate sodium meglumine, and ioxaglate sodium meglumine) contrast media, was visually inspected at predetermined time intervals before and after mixing. Aliquots of the mixtures of blood and contrast media also were evaluated microscopically. Irregular red blood cell (RBC) aggregates were observed with the nonionic contrast media. Pronounced RBC morphologic alterations occurred with diatrizoate (ionic), and marked crenation was observed with ioxaglate (ionic). Observed aggregates were freely disaggregated in isotonic saline. Recovered supernatant blood from centrifuged aliquots of the mixtures was evaluated for clot formation. There was no evidence of blood clot formation within 1 hour after blood was introduced into syringes containing either ionic or nonionic contrast media. This time period exceeded the normal clotting time, since blood in syringes without contrast media formed clots within 30 to 45 minutes. Both the nonionic and ionic contrast media prolonged coagulation.

Blood Coagulation↗
PubMed1988

Effects of contrast media on erythrocyte and platelet interactions with endothelial cell monolayers exposed to flowing blood.

Although there have been reports of clot formation in angiographic syringes containing nonionic contrast agents, these clots are now believed to be aggregates of red cells that form in the low ionic strength, low pH, zero shear rate environment of contrast media syringes. In an in vitro controlled flow system that stimulates blood flow through a microvessel, we found that large (100 microns or more) red cell aggregates are not seen with any of the media tested (iohexol, sodium methylglucamine diatrizoate, and ioxaglate); aggregates that form under shear conditions are rouleaux. The degree of rouleau formation, compared with saline controls, is greatest with ioxaglate, least with diatrizoate, and intermediate with iohexol. Platelet adhesion/aggregation at a site of injury to vascular endothelium is not significantly affected by iohexol. Rouleaux formation, a potential determinant of local levels of thrombin and other platelet-activating substances, is shown to occur in the lee of mural platelet thrombi.

Blood Circulation↗
PubMed1989

Nonselective digital subtraction angiography. Compact contrast material bolus for improved image quality.

Digital subtraction angiography (DSA) examinations of major aortic branch vessels traditionally have been performed with aortic injections of dilute contrast material (70-150 mg I/mL) over approximately 2 seconds. This study examines a technique employing rapid boluses of undiluted contrast material (282-300 mg I/mL) in small volumes and compares the quality of the images to those obtained using conventional methods. Twenty intra-aortic DSA angiograms of the renal arteries were performed in 10 patients. In each patient, both compact bolus and conventional injections were performed. Injections of 12 or 15 mL of diatrizoate meglumine-60% at 30 mL/second (duration = 0.4 or 0.5 seconds) were compared with injections of 24 or 30 mL of diatrizoate meglumine-30% at 12 mL/second (duration = 2 seconds). Aside from injection technique and image projection, no other variables were altered, and the iodine loads were the same for the two injections in each patient. The images were paired and rated by four radiologists without knowledge of the technical parameters. The radiologists overwhelmingly preferred the images corresponding to the compact bolus technique (Chi-square analysis P less than .001). Visualization of the main renal arteries and the intrarenal branches was improved (P less than .001 for both). A reduction in misregistration artifact is suggested but not statistically significant. We conclude that image quality in nonselective, intra-arterial DSA can be improved without an increase in iodine dosage by the rapid administration of undiluted contrast material in small volumes.

Adult↗
PubMed1989

Penetration of vascular contrast media into brain tissue and cerebrospinal fluid. An experimental study in rats.

Recent studies suggest that intravenously administered contrast media (CM) penetrate into cerebrospinal fluid (CSF), and the concentration of CM in CSF increases significantly following acetazolamide or probenecid pretreatment. However, corresponding levels of CM in brain tissue and extracellular fluid (ECF) have not been reported. Adult anesthetized rats were injected intravenously with sodium/meglumine diatrizoate and iohexol. The control group received no pretreatment, and the pretreated group received acetazolamide and probenecid before the CM. The amount of each contrast agent was measured in brain tissue and in CSF by high performance liquid chromatography. Pretreated animals attained significantly higher CSF concentrations of diatrizoate and iohexol than control animals. However, tissue ECF concentrations in pretreated animals were not significantly different than in control animals for either agent. The results are consistent with the idea that a flushing action of CSF helps to remove CM from the brain ECF.

Acetazolamide↗
PubMed1989

Hemodynamic effects of ioversol in the dog and rat.

The hemodynamic effects of selectively administered ioversol were examined in the dog and rat. At concentrations ranging from 32% to 37% I, wt/vol, ioversol was compared with nonionic (iohexol, iopamidol) and ionic (diatrizoate) contrast media for cardiovascular responses following injections into the femoral vein, right and left coronary arteries, left ventricle, and the pulmonary and femoral arteries of the dog, and into the carotid artery of the rat. Regardless of the intravascular route of injection, ioversol generally caused minimal effects on the heart rate, minimal to moderate decreases in myocardial contractility, left ventricular pressure, mean arterial pressure, pulmonary vascular resistance, and systemic vascular resistance. These effects of ioversol were comparable to those of iohexol and iopamidol, and were relatively less profound than those of diatrizoate. Under experimental conditions injections of ioversol exerted hemodynamic effects comparable to those of other nonionic agents, yet relatively diminished as compared with a representative high-osmolality ionic contrast agent. These results suggest that the nonionic contrast agent, ioversol, should be well tolerated in patients following injections via similar intravascular routes.

Animals↗
PubMed1989

The effect of radiographic contrast media on ultrasonically detectable red blood cell aggregation in vitro.

We investigated the effect of radiographic contrast media (RCM) on red blood cell (RBC) aggregation by analyzing echogenicity of flowing blood before and after the addition of 2%, 20%, 50% or 95% volume of undiluted meglumine diatrizoate, iohexol, sodium meglumine ioxaglate, or iopamidol and equiosmolar volume concentration of saline. This was done both by stepwise increasing the concentration with minimal mixing and by stepwise decreasing the concentrations with more efficient mixing. All contrast media caused a drop in blood echogenicity after a proper mixing when compared with saline addition. After minimal stirring, both meglumine diatrozoate and iohexol caused a significant increase in blood echogenicity at volume concentrations over 50%. The paper demonstrates that earlier findings of both increased and decreased RBC aggregation following exposure to RCM can be reproduced and that the result depends on experimental setup. In diatrizoate and iohexol RBC aggregates disappear after mixing (increasing the shear rate) or when the RCM/blood mixture is diluted. After dispersement, the abnormal RBC aggregates will not reform.

Blood↗
PubMed1990

Effects of angiographic contrast media on venous endothelium of rabbits.

The effects of ionic and nonionic contrast media on rabbit venous endothelium were examined. In anesthetized animals, caudal mesenteric veins were exposed and perfused with the ionic contrast medium, diatrizoate, and the nonionic contrast media iopromide and iotrolan for 2 minutes at 5 mL/minute. Control animals were similarly perfused with physiologic saline or a 23% sorbitol solution. The specimens were fixed in situ by perfusing 4% glutaraldehyde, and ultrathin stained sections were examined with an electron microscope. The hyperosmolar contrast medium diatrizoate produced shrinkage in cell cytoplasm and in nuclear material. There also were minor structural alterations in endoplasmic reticulum and widening of intercellular junctions. The nonionic contrast media iotrolan and iopromide caused mild to moderate changes in endothelial cells. Sorbitol infusion, however, affected venous endothelium more intensely than the ionic and nonionic contrast media, suggesting hyperosmolality as the causal factor in endothelial damage.

Angiography↗
PubMed1990

Extravascular extravasation of radiographic contrast media. Effects of conventional and low-osmolar agents in the rat thigh.

We compared the damage resulting from intradermal injection of four commonly used radiographic contrast media in laboratory rats. Sixty percent meglumine diatrizoate (Reno M 60) and ioxaglate (Hexabrix) produced significantly more ulceration and crusting on gross inspection and more necrosis, edema, and hemorrhage on histologic evaluation than iopamidol 300 (Isovue) or 0.9% (normal) saline. Thirty percent meglumine diatrizoate (Reno M Dip) had an intermediate toxicity, resulting in significantly more visible swelling and more microscopically detected hemorrhage than iopamidol or saline, but less ulceration/crusting and necrosis than Reno M 60 and ioxaglate. Since the three contrast agents of similar osmolality produced different degrees of tissue damage, our results suggest that factors other than high osmolality are partially responsible for determining the severity of injuries from extravasated contrast media.

Animals↗
PubMed1990

A simplified radioenzymatic method for the study of whole blood histamine release in patients receiving radiographic contrast media.

With the availability of a newly developed, histamine-dependent allergy blood test, the authors studied the effect of ionic and nonionic radiocontrast media (RCM) on the in vitro release of histamine from whole blood obtained from 61 patients undergoing diagnostic arteriography. The ionic RCM, sodium meglumine diatrizoate (60 to 378 mmol/L), induced the release of a significantly (P less than .005) higher amount of histamine from blood compared with the nonionic agents, iopamidol and ioversol. Diatrizoate triggered significantly (P less than .05) more histamine release from the blood of eight patients with a history of adverse reactions to RCM than it did in 53 nonreactors; however, there was no appreciable difference in histamine release between reactive and nonreactive groups when stimulated with iopamidol and ioversol.

Contrast Media↗
PubMed1991

Renal tolerance of AMI 25.

The objective of this study was to evaluate the renal tolerance of a new magnetic resonance contrast agent, AMI 25. This agent has an affinity for the reticuloendothelial system and is used for the detection of focal liver lesions. A combination of renal ischemia and intra-arterial iodinated contrast agent infusion (diatrizoate) leads to a reproducible and reversible model of acute renal failure in the rat. Using this model, AMI 25 was perfused directly into the aorta at the dose of 1 ml/kg--ten times the dose used in humans. AMI 25 induced no change in serum creatinine (45 +/- 7, 40 +/- 6, 40 +/- 9 mumol/L before infusion and at 24 and 48 hours, respectively), in creatinine clearance (2.1 +/- 0.6, 2.1 +/- 0.6, 2.1 +/- 0.6 mL/mn), or in urinary N-acetyl glucosaminidase (NAG) excretion (72 +/- 16, 98 +/- 12, 58 +/- 9.8 mumol hour-1/mmol creatinine). Blinded histologic analysis of 11 kidneys perfused with AMI 25 revealed no abnormalities, whereas diatrizoate induced acute tubular necrosis in four of the seven kidneys examined. In our animal model, AMI 25 has no nephrotoxicity, even at ten times the expected clinical dose for humans.

Acetylglucosaminidase↗
PubMed1991

Contrast media-induced renal tubular vacuolization. A light and electron microscopic study on rat kidneys.

The morphologic changes in healthy rat kidneys (n = 102) were studied 2 or 48 hours after intravenous injection of 1 or 3 g iodine (I)/kg of high-osmolality diatrizoate, low-osmolality iopromide and iohexol, or iso-osmolality iotrolan, as well as after 0.2 or 0.6 g/kg of the high-osmolality magnetic resonance contrast medium gadolinium DTPA. Physiologic saline was injected in controls. The kidneys were fixed by perfusion and the specimens were analyzed semiquantitatively by two independent observers blinded to the treatment. A statistically significant (P less than .01) cytoplasmic vacuolization was noticed in the proximal convoluted tubule cells 2 hours after injection of 3 g I/kg of diatrizoate or iopromide. Iohexol and iotrolan induced an even more significant (P less than .01) and longer-lasting vacuolization, but gadolinium DTPA did not produce lysosomal alterations. Although the vital cell organelles remained intact, reversible lysosomal alterations may represent the first structural signs of a threatening cellular injury.

Acute Kidney Injury↗