Alteration of the ionized calcium level in coronary sinus blood during coronary arteriography]

Injection of contrast medium into the coronary circulation produces a decrease in the concentration of ionized calcium in blood and thus causes a deterioration of myocardial contractility. In this study, changes in the ionized calcium level in the coronary sinus during coronary arteriography were compared for four different contrast media in human subjects. The contrast media used were meglumine sodium diatrizoate, iohexol, iopamidol and meglumine sodium ioxaglate. Blood samples were collected from the coronary sinus before and 5, 15 and 30 seconds after the first injection of contrast medium into the left coronary artery. The ionized calcium level of each specimen was measured using an ion specific electrode, and hematocrit was measured using the centrifuge method. Diatrizoate produced the greatest changes in both hematocrit and ionized calcium. The time concentration curve of hematocrit was similar for all four contrast media, but diatrizoate and ioxaglate produced a prolonged decrease in ionized calcium. The cause of this phenomenon is not clear, but it may be related to differences in the ionic status of the contrast media. Nonionic low-osmolality contrast media with added calcium may be preferable for coronary arteriography with respect to maintenance of the ionized calcium level.     

Ionized calcium levels in coronary sinus blood during coronary angiography: effects of four contrast media.

The changes in ionized calcium level in the coronary sinus during coronary angiography were compared for four contrast media (meglumine sodium diatrizoate, iohexol, iopamidol, and meglumine sodium ioxaglate) in 44 subjects. Blood samples were collected before and 5, 15, and 30 seconds after injection of contrast medium into the left coronary artery. The hematocrit and ionized calcium level of each specimen were measured. Meglumine sodium diatrizoate produced the largest changes in hematocrit and ionized calcium level. The time-concentration curve of the hematocrit was similar for all four contrast media, but diatrizoate and ioxaglate produced a prolonged decrease of ionized calcium. The cause of this is not clear, but the phenomenon may be related to differences of ionic status among the contrast media. With respect to maintenance of the ionized calcium level, nonionic low-osmolality contrast medium with added calcium may be preferable for coronary angiography.     

Incidence of fibrillation with dilute contrast media for intra-arterial coronary digital subtraction angiography

State-of-the-art imaging technology such as digital subtraction angiography can produce coronary artery opacification with contrast media formulations that contain less than 170 mgI/ml. We examined the effect of electrolyte composition in such formulations on the incidence of fibrillation. Right coronary injections of contrast were made for 25 seconds in anesthetized dogs. This injection is longer than clinical injections, but the model approximates the worst condition of a wedged catheter preventing media washout. Formulations of several mixtures of meglumine and sodium diatrizoate (173 to 141 mgI/ml) and sodium diatrizoate alone (143 mgI/ml) produced fibrillation in only 10 to 20% of the injections. Meglumine diatrizoate (141 mgI/ml) and full strength meglumine/sodium diatrizoate (Angiovist 370) produced fibrillation in 100% and 50% of the injections, respectively. These animal studies demonstrate that dilute contrast media containing few or no sodium ions are more likely to induce fibrillation than Angiovist 370, whereas dilute contrast media containing sodium are the least likely to induce fibrillation.     

Iodinated contrast medium-induced potassium release: the effect of mixing ratios

PURPOSE: It has been demonstrated that iodinated contrast medium (CM) causes the release of potassium into the intravascular spaces, resulting in an increase of serum potassium. The purpose of the present study was to assess the effect of mixing ratio on potassium release rates by using various mixing ratios with human blood in vitro. MATERIALS AND METHODS: Fresh human blood from 52 patients was mixed in vitro with iodinated CM at ratios ranging from 10:2 (blood:CM) to 10:10. Potassium release rates were determined during 30 min of exposure to CM. The test solutions used consisted of 370 mgI/ml iopamidol, 320 mgI/ml meglumine/sodium ioxaglate, and 370 mgI/ml meglumine/sodium diatrizoate. RESULTS: Potassium release rates increased gradually from ratios of 10:2 to 10:10. These changes were statistically significant. Among the three CM, diatrizoate induced the greatest potassium release, followed by iopamidol and then ioxaglate. CONCLUSION: Increasing mixing ratios caused an increase in potassium release rates.     

A comparison of the systemic responses to rapid intravenous injections of ioxilan, iohexol, and diatrizoate in rabbits

Rapid intravenous injections of contrast media are used for angiocardiography, intravenous digital subtraction angiography (DSA), and rapid scan computed tomography procedures. These rapid intravenous injections have been shown to produce significant hemodynamic changes that appear related to contrast media osmolality. In this study the systemic responses to 2-second injections at a dose of 1.5 mL/kg were compared for a new nonionic agent, ioxilan (350 mgI/mL), and for iohexol (350 mgI/mL), meglumine/sodium diatrizoate (370 mgI/mL), and saline. Ioxilan has a lower osmolality and viscosity than iohexol and is formulated with a 3 mM sodium citrate as a buffer and anticoagulant. All of the test solutions produced statistically significant changes in arterial pressure and respiratory rate (P less than .05, Student's t-test). The decrease in arterial pressure seen with diatrizoate (20.1%) was significantly greater than the decrease seen with either ioxilan (10.2%) or iohexol (10.2%). All of the responses observed were transient and would not be of clinical concern in a healthy patient. Ioxilan, which contains the calcium binding agent, sodium citrate, and iohexol appear to cause less systemic effects then diatrizoate.     

Calcium binding by gadolinium-based MR contrast agents

PURPOSE: This study was conducted to characterize the alterations in ionic sodium, potassium, and calcium by gadolinium-based MR contrast agents. MATERIALS AND METHODS: An electrolyte solution (ES) containing 1.2 mM/L calcium ions,120 mM/L sodium, and 4.0 mM/L potassium were diluted with various gadolinium compounds and alterations in ionized electrolytes were measured using an ion-specific electrometer. Gadolinium compounds including Gd-DTPA, Gd-DOTA, gadoteridol, gadodiamide, meglumine/sodium diatrizoate (76% Urografin), and isotonic saline as a control were investigated. The dilution ranged from 5% (ES/test solution = 100/5) to 100%. Alterations of ionic electrolytes were measured. Calcium-binding capacities caused by each gadolinium compound also were measured. RESULTS: The alterations of ionic sodium and potassium by gadolinium compound were similar to those of isotonic saline. A significant reduction in ionized calcium was observed with Gd-DTPA and Gd-DOTA in comparison with gadoteridol and gadodiamide. CONCLUSION: Ionic gadolinium compounds induced significant reductions of calcium ions in vitro compared with non-ionic gadolinium compounds.     

Effects of contrast media on the RR and QT interval during coronary arteriography

During coronary arteriography, transient prolongation of the RR and QT intervals can be observed to occur. Animal experiments have suggested that low-osmolality contrast media have less effect, but there have been few clinical studies of this phenomenon. We analyzed 95 electrocardiographic records from patients who had undergone coronary arteriography and assessed the maximal prolongation of the RR and QT intervals. The contrast media used for arteriography included meglumine sodium diatrizoate, iopamidol, iohexol, and meglumine sodium ioxaglate. Diatrizoate caused the greatest electrocardiographic changes. Among the low osmolality contrast media, ioxaglate caused the smallest bradycardial effect and iohexol the smallest prolongation of the QT interval. It appears necessary to consider some additional factors for osmolality or ionicity, such as the chemotoxicity of the chemical structure of the iodinated contrast medium moiety, when assessing their potential adverse effect on the cardiac conduction system.     

Preclinical evaluation of iotrolan as a contrast medium for angiography and urography]

Efficacy and tolerability of iotrolan, a nonionic isotonic dimer, as a contrast medium for angiography and urography were investigated in animals. In the arteriography of rabbit femur, the efficacy of iotrolan 280 mgI/ml was as good as iopamidol 300 mgI/ml and better than meglumine diatrizoate 306 mgI/ml. In rat urography, the efficacy of iotrolan 280 mgI/ml was better than both iopamidol 370 mgI/ml and iohexol 350 mgI/ml. Vascular pain was less with iotrolan 280 mgI/ml than with iohexol 300 mgI/ml in rats. Effect of iotrolan on the pulmo-cardiovascular parameters, arterial pO2, hematocrit and plasma osmolality was less than iopamidol and diatrizoate in rabbits. Iotrolan induced no renal dysfunction and diuresis where iopamidol induced diuresis in rats. Effect of iotrolan on the blood coagulation was similar to nonionic monomers and less than diatrizoate in rabbits. Because of its isotonicity, iotrolan induced little water shift in the blood vessel and urinary tract, which would result in good efficacy and tolerability. These results suggest that iotrolan is superior to ionic and nonionic monomers for angiography and urography.     

Improvement in referral practices elicited by a redesigned request format

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.     

Plasma histamine levels following administration of radiographic contrast media

The effect of two conventional high-osmolality and two new low-osmolality contrast media on plasma histamine levels has been examined. The study population included 25 patients undergoing intravenous urography with Urovison 58% (sodium and meglumine diatrizoate), 24 patients receiving intravenous Hexabrix 320 (sodium and meglumine ioxaglate) for urography, 16 patients receiving intravenous Iopamiro 370 (iopamidol) for urography and 12 patients receiving Urografin 76% (sodium and meglumine diatrizoate) for coronary angiography. Seventy-four percent of the 77 patients studied suffered adverse reactions ranging from a feeling of warmth and nausea to laryngeal oedema and bronchospasm. Hexabrix 320 and Iopamiro 370 were associated with the least patient discomfort. All contrast agents usually produced a rise in plasma histamine following injection (Iopamiro 370 causing the least change) and the histamine levels then fell towards preinjection values over a space of about 10 minutes. No relationship was observed between the magnitude of the increase in histamine and the severity of the reaction that occurred. However, a relationship was suggested between the mean peak plasma histamine level achieved and the occurrence of a Grade II reaction (i.e., dry retching/vomiting, mild urticaria or rash). These findings raise the probability that histamine contributes to the more severe grades of reaction to radiographic contrast media.     

Renografin-60 for urography: effect on serum electrolytes and proteins in adults

A prospective study was done on 27 adults to assess the changes in serum electrolytes and proteins induced by bolus administration of 100 ml of the ionic contrast medium diatrizoate meglumine and sodium (Renografin-60) for IV urography. Statistically significant changes in serum sodium, chloride, potassium, calcium, bicarbonate, phosphate, total proteins, and albumin were shown at 5 min postinjection. The mean percentage decreases were sodium 2%, chloride 2%, potassium 9%, calcium 13%, bicarbonate 9%, phosphate 10%, and proteins 15%. A mean 3% increase in serum osmolality was observed. By 30 min, sodium and chloride levels had returned to baseline; potassium, calcium, and albumin values were incompletely recovered; bicarbonate was not significantly changed from 5 min; and phosphate values continued to decrease. An in vitro dialysis experiment in which different volumes of Renografin-60 were dialysed against an electrolyte solution (pseudoserum) produced a dilutional factor of 5 to render a given volume of the contrast isoosmotic with plasma. The observed changes from the baseline values of the electrolytes and proteins up to 10% are therefore assumed to be due to hemodilution resulting from movement of fluid from the extravascular to the intravascular compartment. This study confirms alterations in serum levels of several electrolytes after the use of ionic contrast media beyond simple hemodilution. Although these changes appear not to be clinically significant in this investigation, the alterations in potassium and calcium may contribute to arrhythmias, particularly when hypokalemia or hypocalcemia preexists.     

Experimental evaluation of iotrolan as an arthrographic contrast medium--knee arthrography with iotrolan in rabbits

Authors evaluated the efficacy and tolerability of iotrolan, a nonionic dimeric contrast medium used for myelography, as an arthrographic contrast medium in comparison with meglumine/sodium diatrizoate and iopamidol in rabbit. Iotrolan (Isovist, 300 mgI/ml) was injected in one knee joint and diatrizoate (Urografin, 292 mgI/ml) or iopamidol (Iopamiron, 300 mgI/ml) in the other at a dose of 1.5 ml/knee. Knee arthrograms were taken 2, 5, 10, 20, 30, 45 and 60 min after injection. Contrast density was determined by measuring the transmission density in the supra-patellar bursa with an image analysis system. The anterior displacement of the patellar from the femur was measured as an indicator of hydrarthrosis. Contrast duration in the supra-patellar bursa was longer with iotrolan than with diatrizoate and iopamidol. Hydrarthrosis was less pronounced with iotrolan than with diatrizoate and iopamidol. These results suggest that iotrolan has the advantage over existing contrast media for arthrography with respect to the efficacy and tolerability.     

Granulocyte adherence is inhibited by radiographic contrast media in vitro.

Different amounts of diatrizoate, ioxaglate, iohexol, iodixanol, NaCl 1,000 mOsm/kg, mannitol 1,098 mOsm/kg, and meglumine (meglumine concentrations corresponding to the content in the diatrizoate solutions) were added to either whole blood or a suspension of granulocytes in autologous plasma, and the adherence to nylon fibers was determined. At high concentrations all the investigated contrast media (CM) inhibited granulocyte adherence. The degree of inhibition was significantly greater when the ionic CM diatrizoate and ioxaglate were used, as compared with the nonionic media. Meglumine solutions at high concentrations also inhibited adherence but significantly less than diatrizoate solutions containing the same amount of meglumine. Diatrizoate showed the greatest inhibitory effect on granulocyte adherence, and significant inhibition could be detected even with a 1.25% solution.     

Pain in peripheral arteriography: an assessment of conventional versus ionic and non-ionic low-osmolality contrast agents

Two low-osmolality contrast agents, ioxaglate meglumine/sodium and iohexol were compared with diatrizoate meglumine/sodium in a controlled double blind study of 126 patients undergoing arteriography for peripheral vascular disease to determine which caused the least pain. Discomfort was assessed by means of a visual analog scale rating pain from 0 to 100. Average values for pain were 39 +/- 27 for diatrizoate, 14 +/- 15 for ioxaglate and 21 +/- 22 for iohexol. We found that both low-osmolality agents caused significantly less pain in peripheral arteriography than the traditional agent. The p values were p less than 0.0005 for ioxaglate and p less than 0.005 for iohexol versus diatrizoate. In addition, ioxaglate was found to cause significantly less pain than iohexol (p less than 0.05) in this patient group.     

The frequency of hyperamylasemia after ERCP with diatrizoate and iohexol

The frequency of hyperamylasemia was examined in 88 consecutive patients undergoing ERCP (endoscopic retrograde cholangio-pancreaticography) using either meglumine diatrizoate at 306 mgI/ml., or iohexol at 240 mgI/ml. There was no difference in the incidence of hyperamylasemia between these two groups of patients, nor did any other factors appear to influence its occurrence. The authors conclude that acute hyperamylasemia after ERCP is a complication of relatively minor importance unlikely to be reduced by the use of low osmolality contrast media.     

Factors modifying contrast media induced fibrillation

Factors effecting contrast media induced ventricular fibrillation were studied in anesthetized dogs using contact time as the measured parameter. Injections of meglumine/sodium diatrizoate (370 mg I/ml) were made into the right coronary artery at 0.4 ml/s until fibrillation occurred. A contrast medium containing calcium chelators was found to produce fibrillation in a significantly shorter contact time than a similar medium without calcium chelators. Pre-treatment by the cardiac glycoside, ouabain, increased the contact time for fibrillation as did the production of a sub-acute infarction in the left coronary artery and a previous fibrillation and resuscitation. The data suggest that calcium binding additives increase the risk of fibrillation while pre-treatment with cardiac glycosides, the presence of stable infarcts in the non-injected areas, or a previous fibrillation and resuscitation do not increase risk.     

Inhibition of platelet function by contrast media: iopamidol and ioxaglate versus iothalamate. Work in progress

The effects of an ionic contrast agent, meglumine iothalamate (Conray-60), and two newer low-osmolality radiographic contrast media, sodium meglumine ioxaglate (Hexabrix) and iopamidol (B-15,000), on platelet aggregation and secretion responses were studied. All three agents inhibited platelet responses during stimulation with adenosine diphosphate (ADP), epinephrine, and collagen. Platelet function was inhibited by iothalamate at concentrations of 11 mg iodine/ml and above, and by the newer agents at concentrations above 30 mg iodine/ml. Addition of exogenous calcium decreased the iothalamate-induced inhibition of aggregation but did not improve dense granule secretion. There was no consistent effect of exogenous calcium on platelet inhibition by iopamidol and ioxaglate. These studies indicate that the newer agents inhibit platelet function less than iothalamate does, and that chelation of Ca2+ may not be the major mechanism of platelet inhibition by contrast agents.     

High dose brain CT with ioxaglate and diatrizoate adverse reactions and effects on urine protein tests

Sodium meglumine ioxaglate (320 or 306 mg I/ml) and meglumine diatrizoate (306 mg I/ml) in an intravenous dose of 2 ml/kg were compared in a randomized double-blind test on the brain CT of 209 patients. Side effects were noted in 56% of the ioxaglate group and 90% of the diatrizoate group. Diatrizoate caused a sensation of heat significantly more often and more intensely, but the frequencies of other side effects did not differ significantly. No severe reactions occurred. The quality of the CT scans was equal. Neither ioxaglate nor diatrizoate impaired renal function. False-positive strip tests and falsely elevated protein values measured by the biuretic method were found in particular in the ioxaglate group. The results of urine protein measurements and strip tests are misleading on the day of the examination with both ioxaglate and diatrizoate.     

Physiologic effects of contrast media in the rabbit

The intravenous administration of contrast media (CM) is often associated with alterations in blood pressure (BP) and heart rate (HR). Osmolality is thought to play a role, but the magnitude and even the direction of change may vary under similar osmotic conditions indicating the involvement of other mechanisms. Conscious rabbits received sodium-meglumine diatrizoate (76%, 1 mL/kg, ear vein) every 10 minutes for 1 hour. A similar injection protocol was performed with normal saline and mannitol (36%), equiosmotic to the contrast agent. BP and HR were monitored continuously. Blood samples were collected at the midpoint between each injection for determination of hematocrit, serum osmolality, and iodine concentration. Group parameters at each time point were compared with the Student's t-test. The administration of mannitol caused changes in serum osmolality, hematocrit, and HR as great or greater than the changes caused by equiosmotic diatrizoate. However, BP increased significantly in the diatrizoate group but not in the mannitol group, relative to normal saline. These results suggest that osmolality is important for certain physiologic changes induced by CM, but that BP changes involve mechanisms in addition to osmolality.     

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.