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PubMed1978

In vitro histamine and serotonin release by radiographic contrast media (RCM). Complement-dependent and -independent release reaction and changes in ultrastructure of human blood cells.

Peripheral leucocytes and platelets from twenty healthy volunteers were incubated in vitro with radiographic contrast media (diatrizoate-Hypaque, iothalamate-Conray and iodipamide-Cholografin) under varying conditions. All radiographic contrast media (RCM) were able to induce histamine release from peripheral leucocytes and the release reaction was dose-dependent. There were individual differences in the sensitivity of leucocytes to different RCM. The highest values (up to 80% histamine release) were found with high concentrations (0.07-0.3 M) of diatrizoate. The addition of normal human serum (NHS) to the reaction mixture led to a further increase in histamine release (P is less than 0.01), probably due to complement activation. The mechanism seems to be mediated by proteins of the alternative pathway, because serum depleted of complement components (factor B, factor D, properdin) did not show this synergistic effect. IgG-depleted serum, however, was able to show the augmented release reaction. Washed platelets incubated with RCM released serotonin in a dose- and time-dependent reaction. The most powerful serotonin-releasing RCM was found to be iodipamide, which produced a release reaction in all people investigated at concentrations of 0.04-0.09 M, while diatrizoate and iothalamate were effective only in half of the tested individuals at high concentrations (0.3 and 0.2 M respectively). The addition of plasma proteins to the reaction mixture inhibited the serotonin release quantitatively. There was no difference in inhibitory potency between autologous and heterologous plasma or serum; sera depleted of various complement components showed similar effects as NHS. The serotonin release was not due to platelet lysis, as determined by the concentration of lactic dehydrogenase present in the supernatant during serotonin release. Incubation of the leucocytes with RCM produced ultrastructural changes, including degranulation of basophils, aggregation of platelets and infiltration of the aggregates by polymorphonuclear leucocytes. The most prominent changes were observed when complement was present in the reaction mixture.

Basophils↗

PubMed1993

Acute electrolyte disturbances in coronary sinus during left coronary arteriography in man.

Electrolyte disturbances, particularly reduction of ionized calcium, induced by iodinated contrast media (CM) are important considerations in coronary arteriography. A study was conducted in 24 patients to evaluate the acute electrolyte alterations in the coronary sinus during left coronary arteriography. During left coronary arteriography, coronary sinus blood was withdrawn for measurement of electrolytes. The CM used were diatrizoate, ioxaglate, iohexol, and iopamidol. The hematocrit was decreased moderately by all 4 CM used at 5 s and returned to the control level at 15 s. The level of ionized calcium was decreased by all CM at 5 s. Prolonged reduction of ionic calcium was observed with diatrizoate and ioxaglate at 15 s. The level of potassium was almost unchanged by diatrizoate and ioxaglate in spite of hemodilution, which may lead us to a hypothesis that potassium can be released from the intracellular spaces such as red blood cells and vascular endothelial cells. Thus the depression of left ventricular function might be caused not only by reduction of ionized calcium, but also by a relative increase in the level of serum potassium.

Adult↗

PubMed1983

Selective coronary arteriography: a clinical comparison of two contrast agents.

The radiopacity and complications of meglumine iothalamate 52% and sodium iothalamate 26% (Vascoray) were compared with those of meglumine diatrizoate 66% and sodium diatrizoate 10% (Renografin -76) in 2258 patients with and without cardiac disease. There was no difference in radiopacity and the type and incidence of adverse reactions were similar, but the frequency was significantly higher (p less than 0.05) with Vascoray in patients with constrictive pericarditis, dissecting aortic aneurysm, and primary pulmonary hypertension. The difference in the frequency of hypotension, sinus bradycardia, and transient asystole in the Renografin -76 and Vascoray groups was statistically significant. Ventricular arrhythmias occurred in 6% of the patients with primary myocardial disease compared to an average of 0.7% in those without this cardiac abnormality (p less than 0.01), but there was no significant difference in the frequency in the two contrast agent groups. All reactions were treated and the studies were performed without mortality. Results of this study show that iothalamate formulation with sodium to meglumine ratio of 1:2 containing 410 mEq/L of sodium (Vascoray) is suitable and safe for clinical use for roentgenographic studies of the heart, and coronary artery circulation.

Adult↗

PubMed1993

Platelet adhesion/aggregation in an in vitro model of coronary artery stenosis.

Platelet adhesion/aggregation (PAA) at a site of coronary artery stenosis is believed to be a process strongly modulated by local shear rates and the functional state of neighboring endothelium. One purpose of the present work, therefore, is to describe an in vitro model for the direct imaging of such PAA. Another is to apply the model to the question as to whether the use of nonionic vs. ionic contrast media (CM) in the presence of vascular endothelium contributes to PAA at the stenosis site. Toward these ends, we utilized a special flow chamber which incorporates a monolayer of endothelial cells (ECs), a step 66% flowpath constriction at a site preadsorbed with microfibrillar collagen, and arterial shear rates. By epifluorescence microscopy and digital image analysis of video recordings, PAA was found to be greater with dysfunctional ECs (pretreated with lysine acetylsalicyclate) than with normal ECs, thereby confirming a modulatory role in PAA of functionally intact ECs. When nonionic (iohexol) or ionic (ioxaglate, diatrizoate) CM was added to the flowing blood at a concentration of 20% by non-red cell volume, PAA was inhibited in the order diatrizoate > ioxaglate > iohexol > saline control. No inhibition by any CM was seen, however, when chamber prefill culture medium containing 20% by volume CM was displaced by CM-free blood, in simulation of bolus administration of CM. In terms of inhibition of PAA during percutaneous transluminal coronary angioplasty (PTCA), therefore, our model provides a conceptual basis by which one may anticipate in flowing blood no clear benefit of ionic over nonionic CM.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗

PubMed1986

Operative cholangiography with an antiseptic contrast solution. An experimental study in dogs.

A new antiseptic contrast material, composed of sodium diatrizoate-meglumine diatrizoate and PVP-iodine solutions, was prepared and tested for operative cholangiography. It was tested in vitro, and in vivo in dogs and displayed satisfactory contrast radiologic features, and strong and rapid bactericidal action without detectable side effects. It seems to be promising in reducing the risk of bacterial spread during cholangiography.

Animals↗

PubMed1988

The effect of lumbar sympathectomy on postsynaptic vascular smooth muscle response in the lower limb in dogs.

The intent of this experiment was to study the postsynaptic vasoactive response to tolazoline hydrochloride and sodium-meglumine diatrizoate (Renografin-76) after a unilateral lumbar sympathectomy in a dog model. Both lower extremities were examined using the video dilution technique before and 1-2 weeks after unilateral lumbar sympathectomy (SE). Results showed (1) resting blood flow in the femoral artery as a percentage of cardiac output did not change after sympathectomy (mean and SD before and after SE: 7.0% +/- 2.3 and 6.0% +/- 2.9 respectively n = 13); (2) the reactive hyperemia in the femoral artery caused by sodium-meglumine diatrizoate (Renografin-76) was unchanged after sympathectomy; (3) the vasodilator effect of tolazoline hydrochloride decreased significantly after sympathectomy (p less than 0.05).

Animals↗

PubMed1981

Differential effects of Renografin-76 on the ischemic and nonischemic myocardium.

The effects of intracoronary diatrizoate meglumine and diatrizoate sodium (Renografin-76) on regional contraction were examined in the normal coronary circulation and during partial (50 percent) coronary occlusion in 11 dogs using strain and length gauges. Intracoronary injections of Renografin-76 (1.5 cc) (1.690 mosM/liter; 0.19 mEq Na/ml), equiosmolar dextrose solution and 0.19 mEq Na+/ml saline solution were made randomly. Renografin-76 caused a decrease in preejection tension to 87.4 +/- 4.3 percent (p less than 0.025), total tension to 74.6 +/- 3.3 percent (p less than 0.01) and ejection tension to 11.9 +/- 12.6 percent (p less than 0.001) of control value. Segment length increased to 106.7 +/- 7.3 percent of control value. These changes lasted only 12 +/- 2 (range 5 to 20) seconds (mean +/- standard error of the mean). During partial coronary occlusion and after injection of Renografin-76, preejection tension decreased from 91.7 +/- 6.3 to 53.8 +/- 3.9 percent (p less than 0.01), total tension from 89.9 +/- 5.0 to 59.7 +/- 3.5 percent (p less than 0.01) and ejection tension from 22.8 +/- 8.1 to 17.8 +/- 10.9 percent, whereas segment length increased from 112.7 +/- 3.7 to 130.7 +/- 4.6 percent (p less than 0.01) of control value. In contrast to findings in the normal coronary circulation, tension and length changes lasted 54 +/- 16 (range 15 to 180) seconds (p less than 0.05). The hyperemic response during normal coronary circulation was completely abolished during partial coronary occlusion. Prior administration of nitroglycerin did not shorten the duration of the myocardial depressant effects of Renografin. Injections of equiosmolar dextrose or saline solution produced qualitatively similar but quantitatively less marked changes. Thus, intracoronary Renografin-76 has an accentuated and prolonged depressant effect on the ischemic as compared with the normally perfused myocardium; this effect is not solely due to its hyperosmolarity or sodium concentration.

Animals↗

PubMed1984

Comparative effects of ionic and nonionic contrast materials on indexes of isovolumic contraction and relaxation in humans.

The effects of contrast media on left ventricular (LV) relaxation as assessed by the time constant of isovolumic relaxation have not previously been studied. A new nonionic contrast agent (iohexol) has been shown to have fewer deleterious effects than standard ionic agents. Nineteen patients received iohexol and sodium meglumine diatrizoate (Renografin-76) in a double-blind, crossover study during left and right coronary arteriography and with simultaneous high-fidelity micromanometer measurements of LV pressure. Neither agent induced significant changes in LV end-diastolic pressure after right or left coronary arteriography. After right coronary arteriography, neither agent produced significant deterioration of peak positive dP/dt or (dP/dt)/DP40 (dP/dt at a developed pressure of 40 mm Hg). However, after right coronary arteriography both agents caused a transient deterioration in peak negative dP/dt and the time constant of isovolumic relaxation (p less than 0.05 at 20 seconds after arteriography). After left coronary arteriography, sodium meglumine diatrizoate induced deterioration of systemic blood pressure (p less than 0.05), peak positive dP/dt (p less than 0.01), (dP/dt)/DP40 (p less than 0.05), peak negative dP/dt (p less than 0.01) and the relaxation time constant (p less than 0.01). These effects were not induced by iohexol. Thus, nonionic contrast media exert negligible alterations on LV function when used for coronary arteriography. The findings are of potential clinical importance in view of the large number of patients with depressed LV function who undergo coronary arteriography.

Coronary Angiography↗

PubMed1995

Effects of ionic and nonionic contrast media on in vitro and in vivo platelet activation.

An increased incidence of thromboembolic events has been associated with nonionic contrast media. Although it has been demonstrated that nonionic contrast media cause significant platelet activation in vitro, there is no reported evidence of contrast-induced platelet activation in vivo. This study investigated the effect of a nonionic contrast agent, iohexol (Omnipaque), versus an ionic contrast agent, diatrizoate meglumine+diatrizoate sodium (MD-76), on both in vitro and in vivo platelet activity. Blood from normal subjects (n = 12) was incubated in vitro for 15 to 60 seconds with varying proportions of contrast media or saline solution, and analyzed by flow cytometry for markers of platelet degranulation (P-selectin) and platelet GPIIb-IIIa receptor activation (PAC-1). In vivo activation after Omnipaque was measured in patients undergoing cardiac catheterization in peripheral blood before and after contrast (n = 5), and in coronary sinus blood before and after left coronary injections (n = 8). In vitro data showed that Omnipaque incubated for 60 seconds with whole blood at ratios of 1:1 resulted in a greater percentage of platelets expressing P-selectin (median/range) than did MD-76 (68%/38% to 90% vs 17%/1% to 53%, respectively, p < 0.01). Similarly at a contrast: blood ratio of 1:3, Omnipaque caused greater P-selectin expression than did MD-76 (49%/19% to 83% vs 3%/0% to 5%, respectively, p < 0.05). There was no significant increase in platelet degranulation observed with concentrations of contrast more dilute than 1:3. In addition, there was significantly less activation seen even at contrast:blood ratios of 1:1 when exposure time was < 60 seconds (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Effect of calcium-binding additives on ventricular fibrillation and repolarization changes during coronary angiography.

Ventricular fibrillation during coronary angiography with Renografin-76 (meglumine sodium diatrizoate) has been attributed to the calcium-binding additives sodium citrate and sodium ethylenediaminetetraacetic acid (EDTA), which may produce repolarization changes manifested as prolongation of the QT interval. Angiovist-370 is a newer form of meglumine sodium diatrizoate that contains calcium EDTA as its additive and thus has a decreased calcium-binding effect. Eight hundred sixteen patients were prospectively randomized to receive either Renografin-76 or Angiovist-370. Ventricular fibrillation occurred in 10 of 410 patients receiving Renografin-76 and in 0 of 406 patients given Angiovist-370 (p less than 0.0005). Clinical data were analyzed without knowledge of other data in the 10 patients treated with Renografin-76 who had ventricular fibrillation (Group I), 103 randomly selected patients who also received Renografin-76 but had no ventricular fibrillation (Group II) and 108 randomly selected patients given Angiovist-370 (Group III). Of several variables examined, only the QT interval differentiated patients receiving Renografin-76 and Angiovist-370. The mean corrected QT interval (QTc interval) before coronary angiography was slightly but not significantly (p = 0.7) higher in Group I than in Groups II and III. Ten seconds after the first left coronary artery injection it was more prolonged in Groups I and II (0.552 and 0.561 second, respectively) than in Group III (0.448 second) (p less than 0.00005). Similarly, 10 seconds after the first right coronary artery injection it was significantly longer in Groups I and II (0.545 and 0.544 second) than in Group III (0.477 second) (p less than 0.00005).(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

PubMed1995

Bronchial arterial response to contrast medium.

RATIONALE AND OBJECTIVES: Contrast agents have been shown to produce vasodilatory responses in several vascular beds. To our knowledge, however, their effect on the bronchial vasculature has not been examined. Clinically, contrast-induced bronchial vasodilation could potentially exacerbate life-threatening pulmonary hemorrhage during bronchial angiography for hemoptysis. In the current study, we systematically measured the bronchial vasodilatory response to diatrizoate meglumine 66% and diatrizoate sodium 10% (MD-76) and examined whether vasodilation would be mediated by nitric oxide (NO). METHODS: We measured bronchial blood flow in seven anesthetized, ventilated, open-chested sheep using an ultrasonic flow probe placed around the bronchial artery. Bronchial blood flow was recorded before and after injection of 2 ml MD-76 into the bronchial artery. The protocol was repeated after 20 min infusion of N omega-nitro-L-arginine (L-NA; 10(-2) mol/l), an NO-synthase inhibitor, into the bronchial artery. RESULTS: There was a 45 +/- 8 ml/min increase (p < .01) in bronchial blood flow after injection of MD-76, which was reduced to 20 +/- 6 ml/min (p < .01) after infusion of L-NA. CONCLUSION: Bronchial arterial injection of MD-76 results in a consistent increase in bronchial blood flow that is mediated partly by NO.

Animals↗

PubMed1982

Low risk of contrast media-induced acute renal failure in nonazotemic type 2 diabetes mellitus.

The risk of developing contrast media-induced acute renal failure was studied in 49 randomly selected nonazotemic type 2 adult diabetic patients subjected to IVU. There were 19 men and 30 women in the group whose mean age was 62 +/- 10 years (range, 38 to 82 years). In preparation for IVU, patients were neither dehydrated nor given a laxative. The IVU was performed in the morning, using sodium diatrizoate and meglumine diatrizoate. Serum creatinine levels were measured pre-IVU and on days 1, 3, and 6 after the IVU. A total of three patients (6%) had an elevation of serum creatinine greater than 25% above the baseline by post-IVU day 3. One patient developed oliguria (less than 400 ml/24 hr) that lasted 2 days. Creatinine clearances of the three patients showing contrast media toxicity were 74, 60, and 105 ml/min pre-IVU. In each of the three patients, a return to pre-IVU serum creatinine concentration was noted within 2 weeks. It is concluded that the risk of acute renal failure post-IVU is small in hydrated nonazotemic type 2 diabetic patients.

Acute Kidney Injury↗

PubMedDate not supplied

Balloon-occlusion superior mesenteric arteriography for improved visualization of the mesenteric and portal venous anatomy of dogs.

The superior mesenteric arteries of twelve dogs were occluded with an inflated balloon on the tip of an endhole catheter while diatrizoate meglumine and diatrizoate sodium (Renografin 76) was injected distal to the occlusion. The balloon was immediately deflated at the end of contrast injection. Films taken over a 33-second period showed consistently excellent visualization of the mesenteric arteries and veins as well as the portal veins. Comparison with studies performed by the conventional, nonocclusion technique confirmed the superiority of the films obtained with the balloon occlusion method. Histologic examination of the mesenteric artery at the site of balloon inflation and of the small and large bowel revealed no abnormalities.

Angiography↗

PubMedDate not supplied

Effects of ionic and nonionic contrast agents on left ventricular and extracellular fluid dynamics during angiocardiography in an infant model.

Concern for side effects of contrast materials limits the volume that can be used for angiocardiography in infants; many of these effects are related to hyperosmolality. The effects of intracardiac injections of ionic (meglumine sodium diatrizoate) and nonionic (metrizamide) contrast agents on the left ventricle and body fluids were compared in an infant model. Immediately after injection, meglumine sodium diatrizoate (MSD) caused increases in left ventricular peak systolic pressure (LVPSP) (+26 +/- 5%) (control (C) = 92 mmHg), LV dp/dt (+21 +/- 6%) (C = 2610 mmHg/sec), left ventricular end-diastolic dimension (LVEDD) (+31 +/- 5%) (C = 10.5 mm), and left ventricular end-systolic dimension (LVESD) (+28 +/- 6%) (C = 7mm). Subsequently, LVPSP and dp/dt decreased to -16 +/- 6% and -23 4 +/- 6% of control, while LVEDD and LVESD rose. Dimension changes resolved by 15 minutes. Metrizamide caused immediate increases in LVPSP (+27 +/- 4%) (C = 86 mmHg) and LV dp/dt(+25 +/- 4%) (C = 2640 mmHg/sec). These parameters never declined significantly below control levels and were at control level at 15 seconds. Initial increases in LVEDD (+17 +/- 3%) (C = 10 mm) and LVESD (+6 less than 4%) (C = 6.5 mm) with metrizamide were significantly less than with MSD (P less than 0.008). MSD caused greater and more persistent elevations of serum osmolalities than metrizamide. Differences between the two agents were accentuated during systemic hypoxemia. Thus, ionic contrast agents appear to have a greater propensity for inducing toxic cardiovascular effects in infants than nonionic agents.

Angiocardiography↗

PubMedDate not supplied

The aggravating effect of dehydration on pulmonary edema induced by ionic and nonionic contrast media.

High intravenous doses of diatrizoate are known to induce a profound degree of pulmonary edema in the rat. In euhydrated rats, similar doses of iohexol do not induce significantly higher lung weights when compared with nontreated animals. However, for dehydrated rats, intravenous administration of equivalent doses of these agents results in significant pulmonary edema formation with iohexol, and enhanced edema with diatrizoate; the same magnitude of response is not seen in euhydrated rats. These results show that patients susceptible to severe contrast reactions should be well-hydrated and preferably given a nonionic agent when contrast material must be administered.

Animals↗

PubMed1985

Effects of intravenous administration of a new nonionic dimeric contrast medium on the coronary circulation. Comparison with monomeric ionic and nonionic media.

Contrast media injected into the circulation produce a variety of cardiovascular effects. Agents with low osmolality and low concentrations of cations cause considerably less hemodynamic effects. This study compared the effects of a nonionic dimer, iotrol, which has an osmolality (340 mosm/kg) close to that of serum (290 mosm/kg), with a standard ionic monomer, meglumine diatrizoate, and a nonionic monomer, iosimide. The effects of intravenous bolus injection of these three contrast agents on coronary and systemic hemodynamics were studied in eight anesthetized dogs. The influence of the contrast media on subendocardial and subepicardial perfusion was assessed by injecting radioactive microspheres into the left atrium 30 seconds after injection of the media. Alterations in coronary hemodynamics occurred with both iosimide and meglumine diatrizoate. Iotrol produced minimal changes in coronary hemodynamics. Thus, iotrol is the least perturbing contrast indicator and seems the best for use in quantitative digital subtraction and dynamic computed tomography studies designed to measure myocardial perfusion.

Animals↗

PubMed1985

Contrast enhancement of the liver and blood. Nonionic versus ionic contrast media in the pig.

The contrast enhancement of low-osmolality (iohexol) and high-osmolality (diatrizoate) contrast media was compared in 18 pigs following intravenous bolus administration. Liver and blood attenuation and blood sample iodine concentration were measured during the first 3 minutes after injection. Iohexol produced a significantly higher contrast enhancement in the blood during the period from 0.5 to 3 minutes after injection. Diatrizoate produced a significantly higher contrast enhancement in the liver during the period from 9 to 30 minutes after injection. The greater contrast enhancement of iohexol during the acute phase should be advantageous in dynamic CT.

Animals↗

PubMed1995

Adverse effects of calcium binding contrast agents in diagnostic cardiac angiography. A comparison between formulations with and without calcium binding additives.

RATIONALE AND OBJECTIVES: The authors compared complications and hemodynamic and electrophysiologic effects of two formulations of diatrizoate, one with additives that bind calcium and one without, in diagnostic cardiac angiography. METHODS: Two hundred twenty-three consecutive low-risk patients alternately received Hypaque 76 (group 1, little calcium binding effect), and MD 76 (group 2, significant calcium binding). Electrocardiographic and hemodynamic changes related to coronary angiography and left ventriculography were measured, and complications requiring treatment were recorded. RESULTS: There were more complications in patients in group 2 than in group 1 (18 versus 8, P = 0.04). Arterial pressure fell more, the QT interval increased more, and the heart rate fell more in group 2 after coronary angiography. CONCLUSIONS: Formulations of diatrizoate that minimize calcium binding are advocated for cardiac angiography when using high osmolality contrast media. The more detrimental effects that calcium binding has on myocardial function and cardiac conduction may lead to the higher incidence of complications.

Angina Pectoris↗