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PubMed1983

Systemic hypocalcemia after clinical injections of radiographic contrast media: amelioration by omission of calcium chelating agents.

Intravascular injection of some radiographic contrast media causes a fall in the concentration of unbound serum calcium (Ca++) and an increase in serum immunoreactive parathyroid hormone (iPTH). The decrease in Ca++ levels was attributed to the presence in the contrast media of calcium chelating agents (disodium edetate and sodium citrate) and to the effects of high ionic strength and hemodilution on calcium ion activity. In the present study, we have tested whether omission of the calcium chelating agents from solutions of diatrizoate will lessen the alterations in systemic calcium metabolism. We compared Renografin-76 (RG-76) (diatrizoate meglumine and diatrizoate sodium), which contains disodium edetate and sodium citrate, with Hypaque-76 (H-76) (diatrizoate meglumine, diatrizoate sodium), which contains no calcium chelating activity. A bolus injection of a mean dose of 62 ml of either contrast medium decreased levels of Ca++ significantly (P less than 0.01) at five minutes. The decrease was significantly greater (P less than 0.025) with RG-76 (0.096 +/- 0.018 mM, mean +/- SE) than it was with H-76 (0.049 +/- 0.018 mM, mean +/- SE). The level of iPTH increased (P less than 0.01) by 68 +/- 13 nanoliter equivalents (nleq) per ml with RG-76 and by 28 +/- 8 nleq per ml with H-76 (P less than 0.01 vs RG-76). In vitro, RG-76 decreased levels of Ca++ in aqueous calcium solutions 3.7-fold more than did H-76, but neither contrast medium had any direct effect on the parathyroid hormone assay system. Omission of divalent cation chelating agents from solutions of diatrizoate reduces their effects on systemic calcium metabolism.

Adult↗
PubMed1991

Effects of nonionic versus ionic contrast media on complications of percutaneous transluminal coronary angioplasty.

To evaluate the effect of contrast agents on percutaneous transluminal coronary angioplasty (PTCA) complications, 913 patients undergoing 1,058 separate PTCA procedures were prospectively randomized to receive either nonionic iopamidol (Isovue-370) [n = 507 PTCA procedures] or ionic contrast media, meglumine sodium diatrizoate (Renografin-76) [n = 551 PTCA procedures]. Angioplasty operators, technicians, nurses and patients were blinded to the agent used. All patients were pretreated with 0.6 mg of atropine sulfate intravenously before any contrast injections. Hypotension (mean arterial pressure less than 65 mm Hg associated with contrast injections) occurred during 8.5% of PTCA procedures in which the patients were receiving iopamidol and during 9.5% of the procedures in which the patients were given diatrizoate (difference not significant). Bradycardia (heart rate of less than 40 beats/min associated with contrast injections) developed during 5.7% of procedures when patients were given iopamidol and during 5.1% of procedures when patients were given diatrizoate (difference not significant). The need for additional atropine or temporary pacing during the procedure was similar for patients given iopamidol and diatrizoate. The overall incidence of ventricular tachycardia or fibrillation, or both, during the procedure occurred less frequently when iopamidol was used compared with diatrizoate (1 vs 2.5%, p = 0.045). These serious ventricular arrhythmias were attributable to contrast injections in 0.6% of the PTCA procedures when iopamidol was given and in 2.0% of the cases in which diatrizoate was the contrast agent (p = 0.09). Only 1 patient had an allergic reaction to the contrast agent, and this was in a patient who received iopamidol.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMedDate not supplied

ECG changes and arrhythmias induced by ionic and non-ionic contrast media during coronary arteriography in dogs.

Metrizamide (non-ionic, Nyegaard Co., Oslo, Norway), diatrizoate (ionic) and metrizoate (ionic) were selectively injected into the right or the left canine coronary artery. ECG was recorded and external defibrillation was performed whenever ventricular fibrillation occurred. During left coronary injections metrizamide prolonged the PQ and QT intervals less than did the diatrizoate. During right coronary injections metrizamide affected the QT interval less than either diatrizoate and metrizoate. During right coronary infusions metrizamide caused significantly fewer incidences of ventricular fibrillation than diatrizoate. In clinical coronary arteriography it is assumed that metrizamide would generate fewer AV blocks than diatrizoate and fewer incidences of ventricular fibrillation after right coronary injections than diatrizoate. Changes in the PQ and QT intervals during coronary arteriography can be used as tests to predict the safety of new contrast media.

Angiography↗
PubMed1987

Opiate involvement in contrast media-induced blood pressure changes.

The intravenous administration of contrast media (CM) often alters blood pressure (BP). Osmolality plays a role, but the magnitude and even direction of change varies under similar (osmotic) conditions, indicating the involvement of other mechanisms. Male Wistar rats, anesthetized with pentobarbital, received sodium/meglumine diatrizoate, iohexol, or normal saline, 4 ml/kg, via a tail vein, while blood pressure was recorded continuously. Additional groups were pretreated with the opiate antagonist, naloxone (1 mg/kg, IV), or with an equal volume of normal saline 5 minutes prior to the diatrizoate injection. Comparisons of BP change were made with the Student's t-test. Diatrizoate caused a significant (P less than .0002) increase in BP relative to the saline control group, iohexol did not. Thus, the increase with diatrizoate was significantly greater than with iohexol (P less than .00006). Neither the saline nor naloxone pretreatment altered BP significantly. Saline pretreatment did not alter the significant increase in BP produced by the diatrizoate. However, the diatrizoate-induced increase in BP was prevented by the naloxone pretreatment and was significantly less than after the saline pretreatment (P less than .0001). Based on these and previous results, the authors hypothesize that release of endogenous opioids may play a role in BP changes caused by intravenous CM and that significant CM-induced changes may be prevented pharmacologically with the selective opiate blocker, naloxone.

Animals↗
PubMed2003

A new animal model for testing renal tolerance of contrast agents.

RATIONALE AND OBJECTIVES: To develop a new animal model for the evaluation of the renal tolerance of contrast agent and its application to diatrizoate and iotrolan injections in comparison to saline and mannitol solution. MATERIALS AND METHODS: The nephrotoxic potential of intravenously injected contrast agents in Beagle dogs was determined from the effects on the pharmacokinetics of creatinine injected immediately after these agents in comparison with the kinetics of creatinine injected alone. The kinetic parameters evaluated included plasma half-life, volume of distribution, and clearance. In a series of studies, the experimental conditions were optimized in terms of creatinine dose and the effects of diatrizoate, iotrolan, saline, and mannitol solution on the pharmacokinetic parameters of creatinine were determined. RESULTS: Bolus injection of creatinine into dogs followed a dose-linear pharmacokinetic behavior with a terminal half-life of 90 minutes (10 mg/kg) and 108 minutes (20 mg/kg), respectively, and a clearance of 5 mL/min/kg. Injection of diatrizoate decreased the clearance and the half-life of creatinine significantly. A mannitol solution with the same osmolality as diatrizoate showed the same effect whereas physiological saline did not affect pharmacokinetic parameters of creatinine. The isotonic iotrolan was intermediate between saline and diatrizoate in its effects on creatinine clearance. CONCLUSION: The effect of contrast agents on pharmacokinetic parameters of creatinine injected immediately after the administration of the agents in dogs might be a useful model for the evaluation of renal tolerance. In a cross-over study, iotrolan was not statistically separable from diatrizoate.

Animals↗
PubMed1997

Effect of radiographic contrast media on endothelium derived nitric oxide-dependent renal vasodilatation.

The effect of diatrizoate (Urografin325) on the cumulative dose-response curve of the vasodilatory response to acetylcholine was studied in the isolated perfused rat kidney (IPRK). The effect of 1-nitroarginine methyl ester (L-NAME) (10 mumol l-1) on the cumulative concentration-response curve of the vasodilatory response to acetylcholine and sodium nitroprusside was also studied. Acetylcholine is a vasodilator dependent on nitric oxide (NO) synthesis by the endothelium; sodium nitroprusside is a vasodilator not dependent on endogenous NO synthesis and L-NAME is an inhibitor of endogenous NO synthesis. The effect of L-NAME (10 mumol l-1) on the vasodilatory effect of diatrizoate which is observed in the presence of endothelin A receptor antagonist (BQ123, 10 mumol l-1) was also studied. In all experiments an infusion of angiotensin II (5 ng min-1) was maintained to increase the vascular tone of the preparation. Acetylcholine induced vasodilatation and the maximum increase in renal perfusate flow (RPF) was 17.0 +/- 1.7%, (p < 0.05). Diatrizoate (20 mgl ml-1 perfusate concentration) which induced a sustained fall in the RPF (-31.0 +/- 1.7%, p < 0.05) had no effect on the vasodilatory response to acetylcholine, and a similar increase in the RPF (17.8 +/- 2.2%, p < 0.05) was observed. In contrast, L-NAME (10 mumol l-1) completely abolished the vasodilatory effect of acetylcholine and produced instead a modest decrease in RPF by -5.0 +/- 1.7% (p < 0.05). The vasodilatory effect of sodium nitroprusside was not affected by L-NAME, confirming its selectivity as an inhibitor of endogenous NO synthesis in the IPRK. The maximum increase in the RPF induced by sodium nitroprusside was 23.1 +/- 2.0% (p < 0.05) in the absence of L-NAME and 21.2 +/- 2.2% (p < 0.05) in its presence. L-NAME did not interfere with the vasodilatation induced by diatrizoate in the presence of BQ123. In the presence of BQ123 alone the RPF increased from 23.3 +/- 1.4 ml min-1 g-1 to 26.5 +/- 1.0 ml min-1 g-1 (p < 0.05). In the presence of L-NAME and BQ123 the RPF increased from 24.4 +/- 3.0 ml min-1 g-1 to 27.2 +/- 2.7 ml min-1 g-1 (p < 0.05). There was no difference between the two groups (p > 0.05). In conclusion, diatrizoate did not interfere with endothelium derived NO-dependent vasodilatation in the kidney. A reduced production of NO in the vascular endothelium induced by contrast media is unlikely to play any role in the pathophysiology of the increase in renal vascular resistance produced by these agents. The renal vasodilatation induced by diatrizoate is not dependent on endogenous production of NO.

Acetylcholine↗
PubMed2001

Radiographic contrast media induced nephropathy: experimental observations and the protective effect of calcium channel blockers.

Combined acute inhibition of the synthesis of nitric oxide with L-nitroarginine methyl ester (L-NAME) and of prostacycline synthesis with indomethacin predisposes rats to severe renal injury from radiographic contrast media. The reliability of this pharmacological manipulation in the study of radiographic contrast medium induced nephropathy (RCMN) was investigated. Adult male Sprague-Dawley rats were injected with iv L-NAME (10 mg kg(-1)) and iv indomethacin (10 mg kg(-1)) 15 min apart and prior to injection of RCM or normal saline (control group). A dose-dependent reduction in renal function was observed after intravascular injection of the high osmolar RCM diatrizoate (Angiografin, 306 mgI ml(-1)). A significant (p<0.01) increase in serum creatinine (Cr) (from 54.66+/-8.39 micromol l(-1) to 171.96+/-24.49 micromol l(-1) and from 80.95+/-6.73 micromol l(-1) to 204.76+/-16.73 micromol (-1), n=5 per group) was observed 24 h after injection of 6 ml and 8 ml of diatrizoate, respectively. The increase in serum Cr after injection of 8 ml of diatrizoate recovered spontaneously to 80.87+/-8.70 micromol l(-1) 7 days after injection. No significant change in renal function was observed in the control group (n=5) receiving 8 ml kg(-1) of normal saline or after injection of 4 ml of diatrizoate (serum Cr 69.84+/-5.5 micromol l(-1) pre contrast injection and 66.67+/-13.47 micromol l(-1) 24 h post contrast injection, n=5). The increase in serum Cr observed with 6 ml of diatrizoate was significantly higher (p<0.01) than the rise induced by equivolume of the low osmolar non-ionic monomer iopromide (Ultravist, 300 mgI ml(-1)) (serum CR 68.47+/-8.39 micromol l(-1) pre contrast injection and 143.59+/-32.03 micromol l(-1) 24 h post contrast injection, n=5). The calcium channel blocker diltiazem (10 mg kg(-1) injected intraperitoneally 30 min prior to RCM injection) prevented the rise in serum Cr observed with 6 ml of diatrizoate (serum Cr pre contrast injection 70.31+/-7.28 micromol(-1) and 78.21+/-17.81 micromol(-1) 24 h post contrast injection in animals pre-treated with diltiazem, n=5). The protective effect against RCM-induced reduction in renal function was less with lower doses of diltiazem. In conclusion, the animal model used is reliable and reproduced previously established observations in the field of RCMN. The protective effect of a calcium channel blocker at the appropriate dose against RCMN has also been shown. The clinical effectiveness of this class of drugs in preventing RCMN requires further evaluation.

Animals↗
PubMed1997

Contrast media induced changes in tubular electrophysiology and glomerular filtration rate in the mouse kidney.

The isolated perfused mouse proximal tubule was used to examine electrophysiologic effects of diatrizoate and ioversol. Luminal or basolateral application of diatrizoate resulted in a dose-dependent, reversible hyperpolarization of the proximal tubule cell basolateral membrane potential (VB), which could be abolished by the addition of 10 microM probenecid. While there was a modest reduction in intracellular ATP following a 60-min exposure to diatrizoate, there was no deterioration of VB after 90 min of diatrizoate exposure, even following a 20-min hypoxic insult. Ioversol did not elicit an electrical response. Neither diatrizoate nor ioversol significantly affected transepithelial potential (VT) in the isolated perfused medullary thick ascending limb. In vivo studies showed that only the ionic contrast agent diatrizoate significantly reduced glomerular filtration rate, by 70%. The observed acute contrast media induced reduction in glomerular filtration rate does not appear to depend on direct renal tubular cytotoxicity.

Adenosine Triphosphate↗
PubMed2006

Acute effect of ionic high osmolar contrast medium on renal antioxidant enzyme activity in streptozotocin-induced diabetic rats.

Acute contrast medium-induced nephrotoxicity was estimated in 3%-12% of patients receiving cardiac angiography, especially in advanced age, renal insufficiency and diabetic patients. As intrinsic renal antioxidant enzyme activities may play a crucial role in defence against renal oxidant injury, this study was designed to investigate the acute effect of ionic high osmolar diatrizoate meglumine/diatrizoate sodium on renal antioxidant activities in normal or streptozotocin (STZ)-induced diabetic rats at two time points (1 h and 24 h). A total of 40 Wistar rats were separated to normal and STZ-induced diabetic groups. Ten of each group were injected with diatrizoate (10 ml/kg) via tail vein and 10 with 10 ml/kg of 0.9% NaCl as control. This study shows that diabetic rats had higher renal glutathione peroxidase (GPx) activities than those of normal rats. GPx activities decreased significantly after diatrizoate injection at the first hour (717.4+/-104.0 to 578.6+/-92.1 mU/mg in the diabetic group, 466.4+/-30.6 to 371.4+/-75.5 mU/mg in the normal group, all P=0.032) but the difference faded 24 h later. The increase of superoxide dismutase (SOD) activities was enhanced (673.5+/-100.2 to 750.4+/-129.8 U/mg, P=0.04) in the normal group, but not in the diabetic group (624.1+/-156.6 to 671.1+/-136.7 U/mg, P=0.15) after diatrizoate injection at the first hour. At 24 h, renal SOD activities were still significantly higher in the diatrizoate injection group. In summary, intrinsic renal antioxidant activities are adapted in STZ-induced diabetes and ionic high osmolar diatrizoate could modify their activities. Furthermore, diabetics have abnormal response of renal antioxidant activities by contrast media and are at risk for contrast-mediated nephrotoxicity.

Animals↗
PubMed1995

Cardiac effects of iodixanol compared to those of other nonionic and ionic contrast media on the isolated rat heart.

This study was designed to compare the cardiac electrophysiology and mechanical effects of iodixanol to those of iotrolan, iopromide, ioxaglate and diatrizoate. Two consecutive injections of contrast media (CM) (0.3 g I/kg and 0.9 g I/kg b.w.) were given to spontaneously beating, Langendorff-perfused rat hearts. CM were given as a single, short-lasting bolus injection (i.e. over 2 and 5 s). Changes in aortic pressure, left ventricular pressures and ECG were continuously recorded during constant volume perfusion. The nonionic CM had less pronounced effects on aortic pressure than had the ionic media. The peak rate of isovolumetric contraction (LV dP/dt(max)) was slightly decreased by iodixanol and iotrolan, slightly more decreased by iopromide and markedly decreased by ioxaglate and diatrizoate. Similarly, the peak rate of pressure decline (LV dP/dt (min)) was only slightly decreased by iodixanol and iotrolan. Also, the 2 nonionic dimers had the smallest effects on the left ventricular end diastolic pressure (LVEDP) and heart rate. Ioxaglate lengthened the PQ-interval, but less so than diatrizoate. THe QT-interval was only slightly lengthened by iodixanol and iotrolan, as compared to the lenghthening caused by iopromide, ioxaglate and diatrizoate. Single ventricular extrasystoles were seen in all groups. Extrasystoles up to 3 coupled beats were registered after ioxaglate and diatrizoate. No episodes of ventricular fibrillation occurred with any CM. In conclusion, the nonionic dimers, and in particular iodixanol, induce only minor changes in cardiac function, whereas the ionic dimer ioxaglate and the ionic monomer diatrizoate induce pronounced effects.

Animals↗
PubMedDate not supplied

Water-soluble contrast media in obstructed in ischemic small intestine. A clinical and experimental study.

In this study the attention was focused on the possible application of the new low-osmolar water-soluble contrast media in already existing routines for radiologic diagnostic work-up and management of the abdominal emergencies of simple intestinal obstruction and ischemia: Iohexol was a good, or better, alternative to sodium diatrizoate regarding taste acceptance and patient reactions: Seventy-five per cent of patients characterized the taste of iohexol as good or neutral, while 52% gave sodium diatrizoate similar scores. The scores were also consistently in favor of iohexol as compared with sodium diatrizoate for the other chosen criteria; nausea, vomiting and diarrhea, but a larger number of patients may be needed for conclusive evaluation. Water-soluble media may have therapeutic effects on intestinal obstruction when preceded by conventional gastric suction using a short gastric tube: Twenty-three of 25 patients with subtotal small bowel obstruction due to peritoneal adhesions improved following the ingestion of either iohexol or sodium diatrizoate. Hyperosmolar contrast media might stimulate peristalsis and dilute the bowel contents, hence, easing the passage through a subtotally obstructed bowel. In rats, a direct relationship was found between contrast medium osmolality and the degree of intestinal distension, fluid influx to the bowel lumen and the speed of contrast medium progression. The water-soluble, low-osmolar contrast media seem promising as diagnostic aids in examination of the gastrointestinal tract: The low-osmolar contrast media gave better intestinal details on films than both barium sulphate and sodium diatrizoate in rats with intestinal obstruction or ischemia when high volumes of radiopaques were employed. Also in patients iohexol retained its radiographic density in the small bowel better than sodium diatrizoate. The diagnostic efficacy of the water-soluble radiographic media varied directly with their osmolality and the resulting fluid influx to bowel lumen. Hyperosmolality stimulated contrast medium progression and bowel distension, and reduced the radiographic density of the contrast media and the alignment to the bowel wall. Water-soluble contrast media may aid the diagnosis of bowel ischemia and the evaluation of the degree of ischemic injury: No bladder opacification, following absorption of water-soluble contrast media from the simply obstructed bowel, was observed in the majority of the animals and was only faintly present in 8%. Distinct radiographic opacification of the urinary bladder in rats with intestinal ischemia was demonstrated as early as 1-2 hours after the administration of contrast medium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Product selection criteria for intravascular ionic contrast media.

The chemistry, clinical use, pharmacokinetics, adverse reactions, dosages, and formulary recommendations for intravascular ionic contrast media routinely used in radiologic procedures are reviewed. The meglumine, sodium, or combined meglumine-sodium salts of triiodinated benzoic acid derivatives, diatrizoic and iothalamic acid, are commonly used as intravascular ionic contrast media for radiographic visualization of blood vessels and the urinary tract. Meglumine salts of iodoxamate and iodipamide are used for intravenous cholangiography. The iodine in the contrast medium is responsible for the absorption of x-rays and the resulting opacification of the organ system or other area under investigation. Adverse reactions to intravascular ionic contrast media broadly include hypersensitivity and chemotoxic reactions. The incidence of major life-threatening hypersensitivity reactions, such as severe hypotension, cardiac arrhythmias or arrest, pulmonary or laryngeal edema, and convulsions, is estimated at 0.01-0.1% of the population receiving these agents. Dose- and concentration-dependent chemotoxic reactions result from the direct effects of the contrast medium on the blood vessels or organs being perfused. The meglumine salts of diatrizoic acid and iothalamic acid are less toxic in the cerebral circulation than sodium salts; hence, diatrizoate meglumine or iothalamate meglumine are recommended for cerebral angiography. In coronary angiographic examinations, combined meglumine and sodium (6.6 parts meglumine to 1 part sodium) formulations of diatrizoate are recommended because they consist predominantly of the meglumine salt with minimal but adequate amounts of sodium to prevent ventricular fibrillation. Predominantly meglumine salts of diatrizoic and iothalamic acid are also used for peripheral angiography, computerized tomography, and digital subtraction angiography. The dosages of ionic contrast media vary considerably depending on the nature of the radiological examination, the respective technique employed, and the age and condition of the patient. The cost differences between diatrizoate and iothalamate media are typically minimal. Formulary recommendations regarding the appropriate chemical nature of these media are based on the reported adverse reactions with these agents.

Animals↗
PubMed1998

The influence of radiographic contrast media on some granulocyte functions.

Radiographic CM are used to change the X-ray absorption of tissue. They have been used since the 1930's and today four main types are available. All these CM are derived from one original structure: the 2,4,6 triiodobenzoic acid with the substituents in positions 1,2 and 5 as a carboxylic group or amides. According to the nature of the substituents and the number of aromatic rings, the four different types of CM can be identified. Three of the four types of CM are hyperosmolar, some of the ionic CM contain meglumine and all CM contain calcium disodium EDTA. To fulfil their role in host defence, circulatory PMN must adhere to endothelium of capillaries and venules adjacent to the inflammatory locus, migrate through the vessel wall to the area of inflammation, phagocytose opsonized bacteria, kill ingested organisms and, finally, inactivate their own toxic products to prevent damage to normal tissue. CM should be biologically inert, but many physiological and pathophysiological effects have been described. This review deals with the present knowledge about the influence of CM on PMN. This thesis presents results of the effects of the four main types of CM on PMN exocytosis of elastase and lactoferrin, adherence to nylon fibers, chemotaxis under agarose and phagocytosis of latex particles, as well after in vitro exposure of CM to PMN and after intravascular injection of CM. After in vitro exposure of CM to whole blood, a dose-dependent fall in lactoferrin and elastase concentration was observed, statistically significant for diatrizoate and ioxaglate at high concentrations. I.v. injection of iohexol or ioxaglate resulted in small, although statistical, decreases in lactoferrin concentration in plasma. No differences between the CM groups were seen. PMN adherence to nylon fibers after incubation of CM with whole blood or isolated PMNs was inhibited. The most inhibitive agents were the ionic CM diatrizoate and ioxaglate. The meglumine ion was found to contribute to the inhibitive effect of diatrizoate upon adherence. Following i.v. injection of iohexol or ioxaglate, increased numbers of PMNs, in combination with decreased adherence, were noted with ioxaglate, and the opposite with iohexol. Immediately after arteriography with iohexol and ioxaglate, a small increase of PMN count, in combination with decreased adherence, could be seen. An inhibition of adherence will result in a shift from the marginal to the circulatory pool of PMNs and thus an increase in PMN count. Although statistically significant the changes were minor. A pronounced increase in PMN count was seen 2-5 hours after arteriography in combination with a decrease in adherence. These changes may be due to a release of glucocorticoids from the adrenals in response to the procedure and/or the injection of CM. CMs do not act as chemoattractants. However, when CM are added to the chemoattractant N-fMLP in the under agarose assay, the number of PMNs migrating (density) was lowered, while the distance migrated by the leading front was not affected except for diatrizoate that almost abolished migration. When diatrizoate was added to PMNs, a dose-dependent inhibition was observed. Following i.v. injection of CM, no changes in PMN chemotaxis or changes in the chemoattractive potential of serum could be demonstrated compared to the baseline levels. The ability of PMNs to ingest latex particles after incubation with CM was inhibited in a dose-dependent way. The most inhibitive agents were diatrizoate and ioxaglate. A solution containing the same amount of disodium calcium EDTA as the CM solutions inhibited phagocytosis significantly, although less than the CM solution. Improved phagocytosis was observed in hyperosmolar environments due to NaCl or mannitol at osmolarities higher than 369 mOsm. I.v. injection of ioxaglate or iohexol inhibited the phagocytosis of latex particles by PMNs. The impairment was most pronounced immediately after the injection, and had almost returned to ba

Cell Adhesion↗
PubMed1991

Radiographic contrast agents and platelet function: a quenched-flow study.

Radiographic contrast media (RCM) may alter platelet behavior at concentrations achieved during cardiac angiography. We used quenched-flow aggregometry coupled to single-particle counting to study the influence of RCM on the kinetics of platelet aggregation (less than 5.0 sec) induced by adenosine diphosphate (ADP, 2.86 microM). At a concentration in platelet-rich plasma (PRP) of 5 per cent RCM by volume, platelet aggregation was inhibited by diatrizoate, iopamidol and ioxaglate either directly or following incubation of each contrast agent with PRP for 20 minutes. Diatrizoate inhibited more than did iopamidol or ioxaglate (56 +/- 6, versus 39 +/- 3 and 40 +/- 9 per cent respectively; P less than 0.003, p less than 0.009, n = 20 normal subjects). A small reduction (about 16 per cent) in aggregation velocity occurred within 5 seconds of exposure of PRP to all 3 RCM and the onset time (t) or lag period before aggregation begins was significantly prolonged by diatrizoate (p less than 0.03). The RCM vehicles alone (iodinated moiety removed, osmolality readjusted) had no effect on the ADP-induced aggregation. Platelet counts fell significantly after incubation with diatrizoate (12%; p = 0.04). Our data therefore show that early platelet aggregation was inhibited by 3 commonly-used ionic and nonionic contrast agents. Inhibition was apparently caused by the iodinated contrast molecule, began within seconds of platelet-RCM contact and was independent of vehicle composition. Since diatrizoate inhibited aggregation more than iopamidol or ioxaglate, its use may be of additional value during angiographic procedures in clinical situations involving enhanced platelet activation.

Adult↗
PubMed1984

Direct pharmacologic and osmolal effects of contrast media on the mechanics of heart muscle isolated from cats.

We studied 56 right ventricular papillary muscles isolated from cats to determine whether the direct mechanical effects of contrast media are due to their pharmacologic action or to the hyperosmolality caused by them. A 10% solution of Renografin-76 abruptly decreased force 22% below control, then slowly increased it to 22% above control. To elucidate these changes we also studied: (1) Renografin-60 (lower concentration of diatrizoate); (2) meglumine and diatrizoate; (3) meglumine alone; (4) diatrizoate sodium; (5) ethylene diamine tetra-acetic acid (EDTA) (same concentration as in Renografin-76); (6) sucrose to increase osmolality; and (7) Amipaque (metrizamide), a contrast medium without meglumine or diatrizoate. All solutions containing meglumine, and EDTA alone decreased force. Diatrizoate sodium also decreased force initially, presumably due to the high sodium concentration. Meglumine alone decreased force abruptly and substantially. In contrast, metrizamide and 100 mmol sucrose only increased force. Thus, the abrupt decrease in force was caused by the pharmacologic action of meglumine, EDTA, or high sodium in the contrast media, whereas the slow increase in force was caused by hyperosmolality.

Animals↗
PubMed1993

Multicenter trial of ionic versus nonionic contrast media for cardiac angiography. The Iohexol Cooperative Study.

Contrast agents used for cardiac angiography are different in regard to ionicity, osmolality and physiologic effects. The nonionic contrast media have been shown to have less toxic effects and a better safety profile than do higher osmolar agents. To better assess this risk, clinically stable patients undergoing cardiac angiography were stratified according to the presence of diabetes mellitus, and level of serum creatinine, and then randomized to receive either iohexol (Omnipaque 350) or sodium meglumine diatrizoate (Renografin 76). All adverse events that occurred during and immediately after angiography were tabulated. A multivariate model was used to identify patients at increased risk for adverse outcome. The 1,390 patients were randomized to iohexol (n = 696) or diatrizoate (n = 694). Significant differences were found in the number of patients with contrast media-related adverse (iohexol vs diatrizoate: 10.2 vs 31.6%; p < 0.001) and cardiac adverse (7.2 vs 24.5%; p < 0.001) events. Severe reactions and the need for treatment were more frequent with diatrizoate than with iohexol, but there was no difference in the incidence of death. The presence of New York Heart Association classification 3 or 4 and serum creatinine > or = 1.5 mg/dl predicted a higher incidence of adverse events as a result of contrast media alone. Use of iohexol is associated with a lower incidence of all types of adverse events during cardiac angiography than is diatrizoate.

Adult↗
PubMed1985

Ultrastructural changes in rat aortic endothelium during contrast media infusion.

A rat model was employed to investigate contrast media (CM) induced ultrastructural changes in the vascular endothelium. Ionic contrast materials such as Renografin-76 (diatrizoate meglumine diatrizoate sodium), MD-76 (diatrizoate meglumine diatrizoate sodium), and Angiovist (meglumine diatrizoate) were injected into the femoral vein of anesthetized male Wistar rats (240-260 g) and allowed to circulate. Control animals were similarly injected with equiosmolar sucrose and physiologic saline. The thorax was opened 15 minutes, 1 hour, and 4 hours postinjection and cardiac perfusion performed using Karnovsky's fixative; the thoracic aorta was then surgically removed, and processed for transmission electron microscopy. All CM produced shrinkage in cell cytoplasm and nuclear structures thereby causing distortions in cell morphology. In control tissues, however, no such ultrastructural damages were noted. Within 15 minutes of CM infusion, electron dense granules were seen on the luminal surface of endothelial cells, in pinocytotic vesicles, as well as in the gap junctions between cells. These observations indicate that contrast media intake occurs via vesicular transport, and through the cell junction.

Animals↗
PubMed2004

Salutary effects of radiopaque contrast media on the survival of random-pattern skin flaps in the rat: an experimental study.

The radiopaque contrast medium diatrizoate, has a vasodilator effect so that it is used in sudden-deafness secondary ischemic injury. However, ischemic problems are encountered, especially when longer flaps are elevated. A longer flap also has ischemic and relatively ischemic tissue, and may obtain some benefit from contrast media. Forty male Sprague-Dawley rats, weighing about 350-400 g, were used, and randomly divided into four groups (n = 10 rats each group): group 1 was the control, group 2 the diatrizoate, group 3 the iopamidol, and group 4 the iothalamate group. A rectangular 3 x 10 cm caudally based dorsal skin flap was elevated, and sutured back to its original place. In the control group, no pharmacologic agent was administered. Sodium-meglumine-diatrizoate 10 mg/kg/day was administered parenterally in the first experimental group (diatrizoate group); iopamidol 10 mg/kg/day in the second experimental group (iopamidol group); and iothalamate sodium 10 mg/kg/day in the third experimental group (iothalamate group) for 7 postoperative days. On postoperative day 7, all flaps were photographed, and the area of flap survival was measured by using a polar planimeter. The results were statistically evaluated with the Kruskal-Wallis test and Mann-Whitney U-test (P = 0.05). The mean flap survival ranged from 79% in the iopamidol group to 83% in the diatrizoate group, and was significantly greater in all experimental groups (P < 0.05) compared to the control group (59%). There was no significant difference between experimental groups (P < 0.05). We believe that radiopaque contrast media have a beneficial effect in improving skin flap viability when distal flap necrosis is a potential complication of longer flaps.

Animals↗