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Coronary arteriography with iotrolan 280, a blood-isotonic, nonionic, dimeric contrast medium: preliminary clinical results.

The effects of coronary arteriography with ionic, monomeric diatrizoate (iodine content, 370 mg/ml; osmolality, 2.10 Osm/kg) and nonionic, dimeric iotrolan (iodine content, 280 mg/ml; osmolality, 0.27 Osm/kg) were intraindividually compared in five patients with coronary heart disease. According to an open protocol, both contrast media were injected into the left (LCA) and right coronary arteries (RCA), 8 ml and 5 ml, respectively. Before, during, and 60 seconds after each injection, electrocardiograms (ECG) were recorded and heart rate and aortic pressure were measured. Whereas diatrizoate markedly decreased heart rate (LCA, -36%; RCA, -20%) and aortic pressure (LCA, -26%; RCA, -16%), iotrolan administration kept heart rate virtually unchanged (+/- 1%) and only slightly increased aortic pressure (LCA, 5%, RCA, 8%). After iotrolan injection ECG changes (axis shift of QRS and T waves) were still demonstrable, yet the effects of diatrizoate proved to be more significant (prolongation of QRS and QT intervals as well as shifts of QRS and T axis). The opacification of the coronary arteries was always more pronounced after diatrizoate due to its higher iodine content, but the contrast produced by iotrolan usually was satisfactory. No side effects were observed during the study. Thus, this isosmotic contrast medium prevents bradycardia and hypotension during coronary arteriography. The lower iodine content, however, leads to poorer contrast compared with conventional contrast media.

Blood Pressure↗

The effect of radiographic contrast agents on bleeding time and platelet aggregation.

The purpose of this study was to determine whether the use of relatively small amounts of radiographic contrast agents may impair hemostasis. Before and after injection of contrast agents, we measured the template bleeding time, platelet count in whole blood and platelet-rich plasma, platelet aggregation induced by epinephrine and adenosine diphosphate (ADP), and percent disaggregation of ADP-induced platelet aggregates in platelet-rich plasma of 18 patients. Ten patients received 50-100 ml of sodium iothalamate (66.8%) for intravenous urography and 8 patients received 125-200 ml of a combination of meglumine diatrizoate (66%) and sodium diatrizoate (10%) for coronary angiography and left ventriculography. Neither group demonstrated a statistically significant mean difference (p greater than 0.05) for any parameter measured before and after administration of the contrast agents. However, 2 patients who received diatrizoate had lengthening of their bleeding times to greater than twice the baseline value without any change in in vitro platelet aggregation. Physicians should be aware of this potential cause of bleeding which could be of particular danger to patients undergoing cardiopulmonary bypass with its inherent hemostatic defects.

Bleeding Time↗

Myocardial risk area and peak gray level measurement by contrast echocardiography: effect of microbubble size and concentration, injection rate, and coronary vasodilation.

Contrast agents were injected via the intracoronary route in eight dogs during two-dimensional echocardiographic imaging to determine the influence of microbubble size and concentration, injection rate, and coronary vasodilation on risk area and peak gray level measurement. At an injection rate at 13 cc/sec, the average background-subtracted peak gray level intensity of hand-agitated diatrizoate meglumine/diatrizoate sodium was significantly (p less than 0.01) higher than that of hand-agitated diatrizoate meglumine/diatrizoate sodium + 0.9% saline, sonicated diatrizoate meglumine/diatrizoate sodium, and sonicated 70% sorbitol. These differences were abolished by the use of 38 cc/sec injection rates and intracoronary injection of adenosine. Perfusion area determinations as assessed by planimetry were unaffected by the contrast agent used, the injection rate, or by intracoronary administration of adenosine. We conclude that risk area measurement by the ultrasound contrast technique is not affected by varying contrast agents, injection rates, or vasodilation. However, peak gray level intensity is variable among contrast agents and may result in variability of time-activity curve analysis.

Animals↗

Comparison of histamine release effects of ionic and non-ionic radiographic contrast media.

Histamine release may underline the side effects (particularly anaphylactoid) of radiographic contrast media. To study the histamine-releasing properties of radiographic contrast media, this study measured the in vitro release of histamine from human basophils incubated with diatrizoate, a standard ionic radiographic contrast agent, and with iopamidol, a newly developed non-ionic contrast agent. The basophils were separated from blood obtained from 16 patients scheduled for coronary angiography. For both diatrizoate and iopamidol, the concentration of histamine released varied as the concentration of radiographic contrast agent was increased from 0.075 M to 0.50 M. At the higher concentrations tested, the percent of histamine released by iopamidol was about half that released by diatrizoate (p less than 0.05). These data suggest that the use of non-ionic contrast media may involve less patient risk from the histamine-mediated allergic and/or hemodynamic side effects associated with radiographic contrast procedures.

Diatrizoate↗

Centrifugation of normal and rheumatoid arthritis blood on Ficoll-Hypaque and Ficoll-Nycodenz solutions.

Attempts to use the rapid single-step Ficoll-Hypaque centrifugation procedure for the purification of mononuclear and polymorphonuclear leucocytes from the blood of normal individuals and rheumatoid arthritis patients have sometimes been unsuccessful, largely because the erythrocytes would not sediment through the centrifugation medium. Re-evaluation of the factors (e.g. Ficoll concentration, temperature, and ratio of the diatrizoate salts) which affect these separations showed that under our conditions it was advantageous to use a medium with a lower viscosity (Ficoll concentration) and/or a higher osmotic strength (increased sodium diatrizoate: meglumine diatrizoate) than had been recommended previously (Ferrante and Thong, 1978; 1980; Ferrante et al., 1982). Higher osmotic strength media must be used for separating the components of blood from rheumatoid arthritis patients than from normal individuals because rheumatoid arthritis erythrocytes have a lower buoyant density than normal erythrocytes.

Arthritis, Rheumatoid↗

High- and low-osmolar contrast agents in urography: a comparison of the appearances with respect to pyelotubular opacification and renal length.

The incidence of pyelotubular opacification and the change in renal length during intravenous urography with iohexol (Omnipaque) was compared with sodium/meglumine diatrizoate (Urografin). Pyelotubular opacification was seen in 14 out of 29 urograms performed with iohexol compared with one out of 28 urograms performed with sodium/meglumine diatrizoate. This increased incidence is statistically significant and has not been previously documented. The increase in renal length following intravenous contrast medium was similar for both iohexol and sodium/meglumine diatrizoate. The significance of these findings with respect to the interpretation of urograms performed with iohexol is discussed.

Adult↗

Clinical comparison of three contrast agents used in cerebral angiography.

A total of 139 cerebral angiograms were performed on patients assigned randomly to three groups. The contrast agents used for these groups included meglumine calcium metrizoate, meglumine diatrizoate and meglumine sodium diatrizoate. Pulse rate and blood pressure readings were taken preceding and following injections and pain and heat sensations were graded. There were no significant differences in incidence of nausea or in changes of blood pressure or pulse rate, or in severity of heat sensations. There was a lower incidence of severe injection pain with meglumine calcium metrizoate than with meglumine sodium diatrizoate.

Blood Pressure↗

Tissue fluid shifts during renal arteriography with conventional and low osmolality agents.

The osmotic effects caused by conventional and low osmolality radiopaque agents have been studied in the isolated perfused canine kidney. Changes in vein flow, hematocrit, osmolality, and iodine content were measured at injection doses of 0.25 and 0.5 ml/kg (300 mgI/ml). Increases in osmolality and decreases in hematocrit were significantly greater with the conventional ionic monomer meglumine/sodium diatrizoate than with the low osmolality agents iohexol, iopamidol, and ioxaglate. The standard renal vein flow response for all agents was an increase (loss of renal water) followed by a decrease (gain of renal water). Diatrizoate produced the greatest increase in outflow at 0.25 ml/kg, but the differences between agents were not statistically significant. At the 0.5 ml/kg dose the differences in peak renal vein flow between agents were negligible. Renal vein iodine was highest with the dimer, ioxaglate and lowest with the diatrizoate. The nonionics iohexol and iopamidol produced essentially the same renal vein iodine levels and clearance. The new low osmolality agents have significantly less effect on osmolality and hematocrit and produce higher venous iodine levels than a conventional ionic monomer. The only difference between the low osmolality agents was the higher venous iodine seen with the dimer ioxaglate.

Angiography↗

Contrast media for CT. An analysis of the early pharmacokinetics.

Iohexol and meglumine-sodium diatrizoate were injected intravenously into 18 pigs as either a 99:1 or 1:99 mixture. Blood samples were taken for 30 minutes and the concentration of each of the two contrast media was measured by means of a double labeling technique with 125I and 131I. Relative concentrations of iohexol were significantly higher during the first 3 minutes when it was injected as a moderately hyperosmolar (99% iohexol) solution than when it was injected as a very hyperosomolar (99% diatrizoate) solution. The greater intravascular dilution of the 99% diatrizoate solution by extravascular water may explain this finding as well as the significantly longer rapid disposition phase and the slightly lower distribution volume of iohexol.

Animals↗

Work in progress: serial evaluation of tumor volume using computed tomography and contrast kinetics.

Computed tomography can be used to evaluate tumor volume changes after therapy. Pre- and posttreatment results are presented for nine human neoplasms. Volume changes are correlated with the behavior of intravenous diatrizoate contrast material. The five-minute diatrizoate distribution volume appears to be a potential contrast material marker for therapeutically induced tumor volume changes. Neoplasms decreasing in volume demonstrate a decrease in the diatrizoate distribution volume; those increasing in volume demonstrate an increase.

Carcinoma, Squamous Cell↗

Peripheral blood eosinophilia associated with gastrointestinal administration of iodinated contrast media.

OBJECTIVE: This study was designed to assess whether gastrointestinal administration of iodinated contrast media results in peripheral blood eosinophilia. MATERIALS AND METHODS: We studied 110 patients in a retrospective review. Diatrizoate meglumine and diatrizoate sodium for abdominal CT were administered to 98 of these patients; 22 of the 98 had also been given the same contrast medium administered by enema. The remaining 12 patients were given diatrizoate sodium for gastrointestinal fluoroscopy. A control group of 65 patients underwent single-contrast barium upper gastrointestinal or enema examinations. WBC and eosinophil counts were determined approximately 24 hr before the examination and every 24 hr thereafter, through the ninth day. RESULTS: Eosinophilia was detected in 17 (15.5%) of 110 patients after gastrointestinal administration of iodinated contrast media. The prevalence of eosinophilia after administration of iodinated contrast media was statistically significantly different compared with that in the control group, in which none of the 65 patients had eosinophilia (p < 0.001). Eosinophilia was detected 48 hr after application of iodinated contrast agents and lasted through the sixth day, with a peak on the fifth day. The prevalence of eosinophilia was independent of route of application, dose, or type of iodinated contrast medium. Eosinophilia in all cases was clinically asymptomatic. CONCLUSION: Eosinophilia that is caused by gastrointestinal administration of iodinated contrast media is a transient, clinically silent phenomenon. It may lead to unnecessary workup for known conditions associated with eosinophilia.

Administration, Oral↗

Prostaglandin levels in human renal venous blood during renal arteriography.

In view of the possible role of prostaglandins (PG) and thromboxane (TX) in the disturbances of renal function and blood flow after the injection of diatrizoate into the renal artery, we have determined the levels of PGE2, 6-keto-PGF1 alpha (a stable metabolite of prostacyclin) and TXB2 in the renal venous blood before, during and after renal arteriography in 12 patients. Radioimmunologically assayed PGE2 was the most abundant prostaglandin in renal venous blood. Lower basal levels of PGs were associated with renal adenocarcinomas or other tumours than non-tumour kidneys. The concentrations of 6-keto-PGF1 alpha and PGF2 alpha rapidly increased after diatrizoate injection and returned to the basal levels within 5 minutes. Slower elevation was noticed in the PGF2 level of 5 tumour kidneys. Renal plasma concentration of TXB2 remained unchanged throughout the study. The rapid elevation of renal venous prostacyclin and PGF2 alpha concentration after the contrast injection may reflect the enhanced intrarenal prostaglandin synthesis or may be secondary to hemodynamic changes in the kidney caused by hypertonic diatrizoate.

6-Ketoprostaglandin F1 alpha↗

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

Intra-arterial digital subtraction angiography (DSA) can produce coronary artery opacification with isotonic contrast media. In this study we have examined the importance of electrolyte composition in isotonic formulations on the incidence of fibrillation. Right coronary injections of media were made for 25 s in anesthetized dogs. Isotonic meglumine diatrizoate and iohexol produced fibrillation in more than 68% of the injections, while sodium diatrizoate, saline, meglumine/sodium ioxaglate and iohexol with added sodium diatrizoate never produced fibrillation. These animal studies demonstrate a significantly higher risk of fibrillation (p less than 0.005) with isotonic nonionic and ionic media not containing sodium ions.

Angiography↗

Pulmonary edema following high intravenous doses of ionic contrast media. Effect of the anion composition and concentration.

High intravenous doses of diatrizoate are known to induce a profound degree of pulmonary edema which is dose- and injection rate-dependent in the rat. In this study, meglumine salts of diatrizoate, iothalamate, and metrizoate were evaluated for their capacity to induce pulmonary edema following intravenous injections. Differences in anion composition or concentration of diatrizoate meglumine/sodium salts did not cause significantly different degrees of pulmonary edema.

Animals↗

Cardiac catheterization dye does not affect serum thyroid hormone concentrations or TSH secretion.

The iodinated contrast agents used in oral cholecystography impair peripheral iodothyronine-5'-deiodinase activity, resulting in a transient decrease in serum 3,5,3'-triiodothyronine (triiodothyronine, T3) and in increases in serum 3,3',5'-triiodothyronine (reverse T3, rT3) and thyroxine (T4) concentrations. A related iodinated contrast agent, diatrizoate, is employed in coronary angiography. The effect of diatrizoate (Renografin-76) on serum T4, T3, rT3, and thyroid stimulating hormone (thyrotropin, TSH) concentrations and the TSH and T3 responses to thyrotropin releasing hormone (TRH) were evaluated in seven euthyroid patients before and on the fifth day following coronary angiography. No significant changes were observed. Thus, diatrizoate, in contrast to the oral cholecystographic agents, appears to have little or no clinically important effect on thyroid hormone metabolism in man.

Aged↗

Atrial natriuretic peptide response to ionic and nonionic contrast left ventriculography.

Atrial natriuretic peptide (ANP) levels were measured prior to and at 1 and 5 minutes postcontrast left ventriculography with an ionic contrast agent (diatrizoate), and a nonionic agent (iopamidol) and the results were compared. Since ionic contrast agents have been found to cause an increase in left ventricular end-diastolic pressure (LVEDP) and nonionic agents have been found to have less of an effect on LVEDP, we investigated the response of ANP levels, which have been found to increase secondary to increased LVEDP (atrial pressure), with both agents. A group of 38 patients who were scheduled for left heart catheterization for suspected coronary artery disease was included (19 in each group) and blood samples for ANP levels were drawn from the left ventricles. At the same time, heart rate, LVEDP, and left ventricular systolic pressure (LVSP) were also measured. It was found that the LVEDP increased significantly for both agents at 1 minute postventriculography, but no further change occurred at 5 min. Heart rate increased significantly in the diatrizoate group at 1 minute with a return of heart rate to preventriculography levels at 5 min, while the ANP level and LVSP remained unchanged at 1 minute postventriculography with both agents but increased significantly at 5 min in the diatrizoate group only. This difference in ANP response is not correlated with the LVEDP. The response of ANP may be related to heart rate and/or LVSP.

Atrial Natriuretic Factor↗

Is nonionic isotonic iohexol the contrast agent of choice for quantitative myocardial videodensitometry?

All currently used contrast media in coronary angiography induce a considerable hyperemic response interfering with the interpretation of circulation times derived from myocardial time-density curves. Aim of this study therefore, was to find a contrast agent with minimal hyperemic response. For this purpose 2, 4 and 6 ml of the nonionic isotonic low iodinated contrast agent iohexol (Omnipaque 140) and 6 ml of a similarly low iodinated but still hypertonic solution of the ionic diatrizoate (Urographin 30%) were administered into the left coronary artery of 8 anesthetized instrumented dogs. Heart rate was held constant by atrial pacing and left ventricular pressure, left ventricular dP/dt and mean and phasic coronary blood flow were recorded. To test the hypothesis that the hyperemic response to nonionic contrast media is partly due to an increase in inotropic state mediated by Ca++ion influx, all measurements were repeated 30 minutes after intracoronary administration of 0.5 mg verapamil. For iohexol the increase in coronary blood flow was small but significant: 12 +/- 7%, 25 +/- 11% and 38 +/- 16% for the 2, 4 and 6 ml administrations, respectively (mean +/- s.d.; p less than 0.01). For the diluted diatrizoate the increase in coronary blood flow was 65 +/- 23%. Increases for currently used contrast agents are on the order of 200-300%. After verapamil, the hyperemic response to iohexol decreased significantly to 9 +/- 5%, 20 +/- 8% and 29 +/- 12% for the 2, 4 and 6 ml administrations, respectively (p less than 0.01). The reaction to diatrizoate was not affected by verapamil. Moreover, there was a significant positive correlation between the increase in coronary blood flow and left ventricular dP/dt max under all conditions for all but one dog. We conclude that the isotonic, low iodinated nonionic contrast agent iohexol has only a moderate influence on coronary blood flow, which can be further attenuated by verapamil. By this approach, a more reliable assessment of circulation times from myocardial time-density curves obtained by digital subtraction angiography and videodensitometry becomes possible.

Angiography↗

Elimination of variable vasomotor tone in studies with repeated quantitative coronary angiography.

In quantitative coronary angiographic studies, unintentional changes of coronary vasomotor tone may have a significant influence on the coronary artery diameters, thereby increasing the variability in the measurements. To obtain objective data on these measurement variabilities, two protocols were designed to assess the influences of ionic and nonionic radiographic contrast media on the mean diameters of angiographically normal coronary arteries. The vessel sizes were determined with the CAAS using automated edge detection techniques. In 21 patients (study no. I), coronary angiograms were taken in identical angiographic projections before (control), and immediately following several (at average 7) subsequent diagnostic dye injections administered over a period of about 7 min. The ionic contrast agent diatrizoate 76% induced a coronary dilation of 19 +/- 7% (mean +/- s.d., p less than 0.001; n = 10); the nonionic agent iopromide 370 increased the coronary artery diameters by only 6 +/- 4% (p less than 0.01; n = 11). In another 11 patients (study no. II) coronary angiograms were obtained using the nonionic contrast medium iopamidol 300 at 5, 8, 10 and 11 min after the control acquisition; this protocol was repeated in the same patients with diatrizoate 76%. With iopamidol, coronary diameter changes were not significant at any time; with diatrizoate, however, coronary dilation was measured at 10 min (2 +/- 2%; p less than 0.01) and at 11 min (10 +/- 3%; p less than 0.001). In a third study it was tested, whether standardization of coronary vasomotor tone (e.g. in coronary angiographic follow-up studies) is possible by the induction of a reproducible maximum coronary dilation with nitrocompounds. In 12 patients, the mean diameters of angiographically normal coronary segments were analyzed before and at various times after i.v. administration (over 4 min) of 0.025 mg SIN-1/kg bodyweight. Coronary dilation was maximal at 10 or 15 min after the onset of the SIN-1-infusion (29 +/- 5%; p less than 0.001). 0.8 mg nitroglycerin given s.l. at 15 min did not further dilate the coronary arteries (28 +/- 7%). One hour after SIN-1, coronary dilation still amounted to an average of 24 +/- 8% (p less than 0.001) and became 'maximal' again, when 0.8 mg nitroglycerin was again administered sublingually (28 +/- 8%; p less than 0.001). In conclusion, short-term variability of coronary vasomotor tone induced by ionic radiographic contrast media can be eliminated by the use of nonionic contrast agents and observation of injection intervals of at least 2 min. In quantitative coronary angiographic follow-up studies, as well as during acute interventions (e.g., PTCA), identical baseline vasomotor tone can be achieved by induction of the maximal coronary dilation using nitrocompounds.

Adult↗