Effects Of Nonionic Contrast Media Research Articles

Deconvolution Analysis of the Non-Ionic Iomeprol, Iobitridol and Iodixanol Contrast Media-Treated Human Whole Blood Thermograms: A Comparative Study.

To study the effect of non-ionic contrast media on anticoagulated and non-anticoagulated human whole blood samples, calorimetric measurements were performed. The anticoagulated plasma showed the greatest fall in the total ΔH after Iodixanol treatment. The plasma-free erythrocytes revealed a pronounced shift in the Tmax and a decrease in the ΔH of hemoglobin and transferrin. The total ΔH of Iodixanol treatment showed the highest decline, while Iomeprol and Iobitridol had fewer adverse effects. Similarly, the non-anticoagulated samples revealed a decrease both in the Tmax and the ΔH of albumin and immunoglobulin-specific transitions. The total ΔH showed that Iodixanol had more influence on the serum. The serum-free erythrocyte samples resulted in a significant drop in the Tmax of erythrocyte and transferrin (~5-6 °C). The ΔH of deconvolved hemoglobin and transferrin decreased considerably; however, the ΔH of albumin increased. Surprisingly, compared to Iomeprol and Iobitridol treatments, the total ΔH of Iodixanol was less pronounced in the non-anticoagulated erythrocyte samples. In sum, each non-ionic contrast medium affected the thermal stability of anticoagulated and non-anticoagulated erythrocyte proteins. Interestingly, Iodixanol treatment caused more significant effects. These findings suggest that conformational changes in blood components can occur, which can potentially lead to the increased prevalence of cardiovascular dysfunctions and blood clotting.

The effects of non-ionic contrast medium on the hemorheology in vitro and in vivo

Contrast media are the commonly used agents in radiology. However, because of their characteristics of high osmolality, high viscosity, and chemical toxicity, the administrations of contrast media have been shown to cause adverse effects especially on hemorheology in short time course. The present study is to find the effects of a non-ionic contrast medium, iopromide, on the hemorheology in long time course both in vitro and in vivo. For in vitro treatment, human peripheral blood samples were incubated with contrast medium at 37°C for 0.5, 1 and 2 h. For in vivo study, about 15 ml of contrast medium was injected into rabbits and blood samples were collected at 0.5, 2, 6, and 24 h after the bolus injection. Hemorheological parameters were examined. Results showed that hematocrit adjusted whole blood viscosity increased significantly at 1 h after in vitro treatment of contrast medium, while it decreased at 0.5 h and remained low till 6 h after bolus injection. Ektacytometer showed that erythrocyte deformability decreased to the lowest level at 2 h in vitro and it dropped at 0.5 h and resumed to normal after 2 h in vivo. Erythrocyte small deformation indices were reduced by contrast medium in both in vitro and in vivo studies. Erythrocyte orientation index was also reduced in in vivo study. Erythrocyte electrophoresis rates at all time points decreased but osmotic fragility did not change in both studies. These impaired hemorheological parameters may disturb the microcirculation and cause adverse effects in patients with kidney diseases.

Toxic effects of a high dose of non-ionic iodinated contrast media on renal glomerular and aortic endothelial cells in aged rats in vivo

Iodinated contrast media (CM) can induce apoptosis and necrosis of renal tubular cells. The injuries of endothelial cells induced by CM on the systemic condition have not been fully understood. To assess the toxic effects of non-ionic CM on the glomerular and aortic endothelial cells, iopromide and iodixanol, two kinds of representative non-ionic CM, were used for the in vivo study. Sixty aged rats were respectively received the agents or normal sodium intravascularly. No obvious apoptosis and morphological change was detected in the glomerular and aortic endothelial cells apart from renal tubules after CM administration. However, expressions of the nitric oxide synthase (eNOS) in glomerular endothelium were decreased at 12 h after CM injection. Furthermore, plasma creatinine and endothelin-1 were increased and plasma nitric oxide (NO) was decreased significantly after CM administration. However, we failed to observe the significant increase of plasma von Willebrand Factor. These results suggest that non-ionic iodinated CM do not induce apoptosis and necrosis of glomerular and aortic endothelial cells in vivo. Decreased eNOS expression and increased plasma endothelin-1 may be involved in non-ionic iodinated CM-induced endothelial dysfunction and kidney injury.

Effects of non-ionic contrast media on the blood flow through the femoral artery of the dog

Effects of non-ionic contrast media on the blood flow through the femoral artery of the dog

Cell-dependent influence on the phagocytosis induced by non-ionic contrast medium injection

Iodinated contrast media (CM) can inhibit phagocytosis. To better understand the importance of this effect upon the elementary defence mechanism, the aim of the study was to compare the in vivo effect of non-ionic CM on the engulfing ability of peripheral blood phagocytic cells from patients undergoing CM-enhanced CT. Neutrophil granulocytes and monocytes from patients' peripheral blood obtained before and 30 min after CM injection were incubated with fluorescent-labelled Escherichia coli bacteria. Both the percentage of cells that engulfed bacteria and the phagocytic activity per cell has been determined by flow cytometry. We found that phagocytosis was greater in neutrophils than in monocytes. CM decreased the percentage of monocytes phagocyting bacteria, both at 4 degrees C (20.3%+/-3.3% versus 16.1%+/-2.0%; p<0.03) and at 37 degrees C (51.6%+/-4.1% versus 47.5%+/-2.6%; p>0.05), and increased the percentage of neutrophils at 4 degrees C (11.8%+/-2.1% versus 14.3%+/-2.2%; p<0.002) and at 37 degrees C (83.1%+/-3.6% versus 85.1%+/-3.2%; p>0.05). The phagocytic activity decreased significantly at 37 degrees C in monocytes (p<0.02), and was not affected in neutrophils. CM injection has different effects on both the percentage of phagocytosing cells and the phagocytic activity in monocytes and neutrophils. The inhibitory effect on monocyte phagocytosis seems to be compensated by neutrophils.

Renal function and cardiac angiography

To study the effect of non-ionic contrast medium on renal function in children with cardiovascular disease. Analysis of renal function in 98 children with cardiovascular disease before and after the use of Iopamidol, Iohexol, and Ioversol was done for angiography. Serum creatinine (s-Cre), urinary N-acetyl-beta-D-glucosaminase (u-NAG), urinary beta 2-microglobulin (u-BMG), and urinary alpha 1-microglobulin (u-AMG) levels were evaluated. Although s-Cre levels remained unchanged, u-NAG/Cre, u-AMG/Cre and u-BMG/Cre significantly increased 12 hours after angiography. Levels of u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre after angiography were significantly higher in neonates and infants (age< 12-months, n=32) than in children (age>1-year, n=61), in patients with more than 5 ml/kg of contrast medium (n=25) than in those with less than 5 ml/kg (n=70) and in cyanotic patients (n=13) than in non-cyanotic (n=80) patients. Transient renal tubular dysfunction occurred in all of these three non-ionic contrast mediums. Although renal tubular function was intact on a long-term basis, one should be careful of contrast medium-induced nephropathy, especially in neonates and infants, in patients receiving more than 5 ml/kg of contrast mediums in total, and in patients with cyanotic heart disease in using non-ionic contrast mediums.

Inhibition of gluconeogenesis and p -aminohipuric acid accumulation in rat renal cortical slices by ionic and nonionic contrast media

Renal dysfunction is a well-recognized complication induced by contrast media (CM). Nonionic CM have been introduced into clinical use to replace conventional ionic CM in an effort to reduce toxicity. However, the nephrotoxic effects of nonionic CM have not been fully evaluated. We previously determined the activities of N-acetyl-beta- d-glucosaminidase and gamma-glutamyltransferase released from rat and human renal slices incubated with contrast media. Dose-dependent enzyme release from renal slices was observed, but there was no statistical difference in the increase of enzyme activities between ionic and nonionic CM. The present experiment was conducted to compare the effects of ionic and nonionic CM on the metabolic function of rat renal slices. Rat renal cortical slices were incubated with ionic CM (diatrizoate, iothalamate) and nonionic CM (iopamidol, iohexol) at 37 degrees C for 90 min. To examine the dose-response effects of CM on gluconeogenesis and p-aminohipuric acid (PAH) accumulation in the rat renal slices, slices were incubated with 30, 60, and 90 mg I/ml of CM. The inhibitory effects of nonionic CM on gluconeogenesis and PAH accumulation were compared with those of ionic CM in an independent experiment, in which slices were incubated with CM at a concentration of 60 mg I/ml. In addition, rat renal slices were incubated with mannitol instead of CM to investigate the effects of osmotic pressure on gluconeogenesis and PAH accumulation. A dose-dependent reduction of gluconeogenesis in rat renal slices was demonstrated by both ionic CM and nonionic CM. The inhibition of PAH accumulation was dose-dependent with nonionic CM, but not with ionic CM. Gluconeogenesis and PAH accumulation within the renal slices were both inhibited according to the increase in osmotic pressure produced by mannitol. The reduction in gluconeogenesis and PAH accumulation within the rat renal slices incubated with 60 mg I/ml of nonionic CM were significantly less than those resulting from the same concentration of ionic CM. Nonionic CM is less nephrotoxic than ionic CM with regard to gluconeogenesis and PAH accumulation in rat renal slices. These differences in nephrotoxic effect between ionic and nonionic CM may in part be attributable to differences in osmotic pressure.

Nonionic contrast media are less nephrotoxic than ionic contrast media to rat renal cortical slices

Background: Nephrotoxicity induced by contrast media (CM) is well recognized. Nonionic CM with lower osmolality than that of conventional ionic CM have been developed in an effort to reduce toxicity. However, the nephrotoxic effects of nonionic CM have not been well evaluated. Although our previous experiments using rat renal cortical slices indicated that the direct cellular toxicity of nonionic CM is less than that of ionic CM, it was suggested that the less toxic effects of nonionic CM on the metabolic function of renal epithelial cells were in part attributable to the lower osmolality of nonionic CM. In the present experiment, the direct toxicity of nonionic CM on renal epithelial cells was compared with that of ionic CM under equiosmolar conditions, where the effects of osmotic pressure were excluded. Methods: Rat renal cortical slices were incubated with several kinds of CM at 37 °C for 120 min. Diatrizoate and iothalamate were employed as ionic CM. Iopamidol and iohexol were employed as nonionic CM. The activities of N-acetyl-β- d-glucosaminidase (NAG), γ-glutamyltransferase (GGTP), and lactate dehydrogenase (LDH) released from the renal slices into the incubation buffer were determined in order to evaluate renal epithelial damage caused by CM. Gluconeogenesis, p-aminohippuric (PAH) acid accumulation and ATP content in rat renal slices were determined with a view to examine the inhibitory effects of CM on the metabolic function of renal epithelial cells. The toxic effects of nonionic CM were compared with those of ionic CM under equiosmolar conditions, where mannitol was added to the experimental groups containing nonionic CM in order to exclude the effects of osmotic pressure. Results: A significant difference was generally not found with regard to enzyme release between ionic CM and nonionic CM plus mannitol. The inhibition of gluconeogenesis and PAH accumulation in rat renal slices by nonionic CM with mannitol was less than that by ionic CM. Although the ATP content was reduced by both ionic CM and nonionic CM plus mannitol, there was no significant difference between these two groups. Conclusions: The present experiments demonstrated that nonionic CM were less nephrotoxic than ionic CM with regard to the function of renal epithelial cells, including gluconeogenesis and PAH accumulation, under equiosmolar conditions. These differences in nephrotoxicity between ionic and nonionic CM cannot be fully attributable to differences in osmotic pressure.

Nephrotoxic effects of ionic and nonionic contrast media on rat and human renal cortical slices

Background. Nephrotoxicity is a well-known adverse effect of radiographic contrast medium (CM). Recently, several kinds of low- osmolality nonionic CM have been developed. However, the nephrotoxic effects of nonionic CM compared with those of ionic CM have not been well evaluated. Methods. To compare the direct nephrotoxic effects of ionic and nonionic CM on renal epithelial cells, rat and human renal cortical slices were incubated with CM at 37°C for 120 min. Diatrizoate and iothalamate were employed as ionic CM. Iopamidol, iohexol, iomeprol, ioversol, iopromide, and ioxilan were employed as nonionic CM. Direct toxicity of CM was evaluated by the activities of N-acetyl-β-D-glucosaminidase (NAG) and γ-glutamyl-transferase (GGT) released from the renal slices into the incubation buffer. Results. In the experiment with rat renal slices, NAG and GGT activities in buffer solutions were increased dose-dependently by 30, 60, and 90 mg I/ml of CM. There was no significant difference in NAG or GGT release between ionic and nonionic CM at the concentration of 60 mg I/ml. In the experiment with human renal slices, incubation with 60 mg I/ml of diatrizoate, iothalamate, iomeprol, and iopromide did not affect NAG levels. Significantly greater increases in NAG levels, compared with the control, were observed after incubation with iopamidol, iohexol, ioxilan and ioversol. Nevertheless, the increases in NAG caused by some of the nonionic CM were very slight. GGT release from human renal slices was significantly greater than that of the control in all experimental groups. Again, there was no significant difference in renal toxicity between ionic and nonionic CM. Conclusions. Newly developed nonionic CM had almost the same degree of nephrotoxicity against rat and human renal epithelial cells as conventional ionic CM, when direct renal toxicity was evaluated by enzyme release in an in-vitro experimental system using renal cortical slices.

Effects of nonionic contrast media on platelet aggregation: assessment by particle counting with laser-light scattering.

Intravascular radiographic contrast media used in angiography, particularly nonionic contrast media, may cause activation of platelets. This study was designed to determine which properties of nonionic contrast media were potentially responsible for this action. Platelet aggregation after adenosine diphosphate stimulation was studied in the platelet rich plasma obtained from 37 patients who underwent left ventriculography using the highly sensitive method of particle counting with laser-light scattering. Platelet activation by contrast media was studied in the platelet rich plasma from healthy volunteers using flow cytometric analysis to detect platelet degranulation as P-selectin expression. There was a significant decrease in platelet aggregation in patients injected with ioxilan or iomeprol compared with patients injected with iohexol. There was a significant increase in P-selectin expression with the three groups of contrast media compared to control. The platelet activation with ioxilan or iomeprol was significantly less compared to the activation with iohexol. The comparison showed that previous generalization regarding platelet activation by nonionic contrast media might not be valid. It is presumed that the higher osmolality of iohexol may contribute to the increase in platelet aggregation and activation.

Pheochromocytoma: effect of nonionic contrast medium in CT on circulating catecholamine levels.

To study the catecholamine-releasing effect of peripheral intravenous administration of the nonionic contrast medium iohexol in patients with pheochromocytomas. Ten patients (eight women, two men; mean age, 44 years; age range, 25-70 years) with pheochromocytomas and related tumors and six healthy volunteers (five men, one woman; mean age, 31 years; age range, 27-35 years) were examined. Plasma catecholamine levels were measured at intervals for 60 minutes after the injection of 0.9% saline or iohexol on 2 separate days. All 10 patients intravenously received the specific alpha-adrenergic blocker phenoxybenzamine hydrochloride (0.5 mg/kg in 250 mL of 5% dextrose infused over 2 hours) 24 hours before iohexol-enhanced computed tomography. There was no statistically significant increase in epinephrine or norepinephrine levels in the patients or the control subjects. While it may be prudent to administer oral alpha- and beta-adrenoceptor antagonists in all patients with a biochemically proved pheochromocytoma to control their symptoms and to prevent a spontaneous adrenergic crisis, specific blockade may not be required before contrast medium-enhanced scanning with iohexol. Although the sample size of this study is relatively small, the results do suggest that in an incidentally detected, clinically silent adrenal mass that may or may not be hypersecreting, the nonionic contrast medium iohexol may be used for scanning without blockade.

Role of adenosine in the renal responses to contrast medium

Despite the development of non-ionic radiographic contrast media (CM), CM-induced nephropathy is a clinically important problem in patients with pre-existing renal insufficiency. We examined the effects of non-ionic CM (iohexol) on renal function in conscious dogs with and without renal insufficiency, and evaluated the effects of a non-selective (theophylline), an A1 selective (KW-3902), and an A2 selective adenosine antagonist (KF17837) on the renal responses to CM. In sham-operated group, iohexol (2 ml/kg/min for 3 min) increased effective renal plasma flow (ERPF) and glomerular filtration rate (GFR), whereas in renal insufficiency group (with subtotal nephrectomy), following transient increases in ERPF and GFR, CM markedly decreased ERPF (-46.5 +/- 6.7%) and GFR (-51.2 +/- 7.1%). In sham-operated group, theophylline and KF17837 markedly attenuated CM-induced increases in ERPF and GFR, while KW-3902 had no effects on CM-induced increases in ERPF or GFR. In renal insufficiency group, initial increases in ERPF and GFR were blunted by theophylline and KF17837. In contrast, the subsequent decreases in ERPF and GFR were attenuated by theophylline (% delta ERPF, -12.2 +/- 3.2% vs. -46.6 +/- 6.7%, P < 0.01; % delta GFR, 4.3 +/- 2.5% vs. -51.0 +/- 7.1%, P < 0.01), and were completely prevented by KW-3902 (% delta ERPF, 10.8 +/- 2.9%; % delta GFR, 23.8 +/- 4.4%), whereas KF17837 aggravated ERPF (-73.3 +/- 5.3%) and GFR (-78.4 +/- 5.3%). These data indicate that in normal renal function, iohexol elicits renal vasodilation by activating mainly the adenosine A2 receptors. In contrast, in impaired renal function, CM induces both A2 and A1 activation; the former is associated with the initial renal vasodilation, while the latter is responsible for the sustained aggravation of renal hemodynamics.

Renal effects of nonionic contrast media after cardioangiography

Renal effects of nonionic contrast media after cardioangiography

Renal Effects of Nonionic Contrast Media after Cardioangiography

A prospective double-blind randomized cardioangiographic study with iopentol and iohexol was performed in 60 patients. Glomerular filtration rate (GFR) was assessed by serum values of creatinine and beta 2-microglobulin (beta 2-MG), estimated creatinine clearance (CCr) according to Cockroft & Gault's formula, and 24 hour CCr. The urinary excretion of albumin, beta 2-MG, and of the renal tubular enzymes alkaline phosphatase (ALP) and N-acetyl-beta-glucosaminidase (NAG) was also measured. Contrary to what has been found after i.v. injections, GFR was reduced by both nonionic contrast media. Serum creatinine (S-Cr) was increased by more than 25% in 6 patients, 3 in each group. CCr was more sensitive than S-Cr and S-beta 2-MG, but this method is less precise because of risk of urine sampling errors. Estimated CCr gave no additional information to S-Cr. The urinary excretion of NAG and ALP was increased. No clinically significant differences between iopentol and iohexol were detected. No correlation was found between the changes in tubular function parameters and changes in GFR. Twenty patients were on calcium channel blockers before the investigation, but this had no protective effect on the renal function parameters.

Renal effects of nonionic contrast media after cardioangiography

Renal effects of nonionic contrast media after cardioangiography

The Effect of Non-Ionic Contrast Media on Q-T Interval and ST-T Wave of ECG during Coronary Angiography

The Effect of Non-Ionic Contrast Media on Q-T Interval and ST-T Wave of ECG during Coronary Angiography

The physiologic effects of nonionic contrast media on the heart.

This article briefly reviews the potential physiologic effects of ionic versus nonionic contrast media on the myocardium. Selection criteria for articles included the use of quantitative measurement techniques, controlled contrast-media doses, and a focus on cardiac mechanical or electrical function. Two important reviews also were used. Most of the data considered represent the results of animal experiments. Nonionic monomer contrast media are associated with markedly less physiologic effect on the heart, compared with ionic agents. For instance, cardiac depression is minimal, and the incidence of arrhythmia and fibrillation is reduced with nonionic agents during coronary arteriography. Nonionic dimer agents with electrolyte supplementation produce even less mechanical and electrical disturbances.

Variation in Hemostatic Parameters after Intra-Arterial and Intravenous Administration of Iodinated Contrast Media

A few case reports have suggested a possible thrombogenic effect of nonionic contrast media. In vitro investigations have lead to conflicting results. The authors performed three ex vivo studies to evaluate the influence of an ionic, ioxaglate, and a nonionic, iopamidol, low-osmolality contrast medium on a series of clotting and fibrinolytic parameters, after intravenous or intra-arterial administration, during routine diagnostic procedures. In the first study, iopamidol was given to 20 consecutive patients through an arterial catheter for digital subtraction arteriography (DSA). In the second study, iopamidol was compared with ioxaglate. The media were randomly and blindly administered intravenously to 21 consecutive patients undergoing brain computed tomography (CT). Finally, ioxaglate was administered intra-arterially to 20 consecutive patients, in a situation comparable with that of the first study. In the first study, a weak anticoagulant effect and an activation of fibrinolysis were found, associated with indirect markers of thrombin generation, such as increased plasma levels of fibrinopeptide A (FpA) and thrombin-antithrombin III complexes (TAT). In the second study, no significant changes were seen with either contrast medium, for thrombin or fibrinolysis activation parameters. In the third study, the intra-arterially administered contrast medium elicited a marked increase of FpA and TAT, together with an anticoagulant effect. Both ionic and nonionic contrast media are able to interfere with the clotting/fibrinolytic system in the general circulation when they are administered to patients at the usual dosages. Ioxaglate shows more marked anticoagulant and thrombin-generating effects than iopamidol. The procedure (ie, arterial catheter versus intravenous infusion) seems to be more important than the category of contrast medium in conditioning the magnitude of these effects.

Effects of Nonionic Contrast Media on the Blood-Brain Barrier Osmolality versus Chemotoxicity

This study was performed to assess the relative contributions of contrast medium osmolality and chemotoxicity to contrast-induced blood-brain barrier (BBB) damage. Experimental carotid angiography was carried out in rabbits with mannitol at an osmolality of 714 mOsm/kg, with the nonionic, monomeric contrast media iohexol and ioversol at similar osmolalities, and with the nonionic, dimeric contrast media iodixanol and iotrolan at osmolalities less than half that of the mannitol. The amount of damage caused by the procedure was assessed by determining the amount of intracerebral extravasation of intravascularly injected technetium-99m-pertechnetate. Mannitol caused no detectable BBB damage, but all four contrast media caused BBB damage that was significantly more severe than that caused by mannitol. The BBB damage caused by carotid angiography with iohexol, ioversol, iodixanol, and iotrolan was not attributable to their osmolalities, but due to some other physical and/or chemical effects of these media on the BBB.

Heparin Pharmacokinetics and in vitro Anticoagulant Activity in Patients Receiving Nonionic Radiographic Contrast Media

Nonionic radiographic contrast media are used frequently in diagnostic and interventional angiography. However, there is concern that they may possess thrombogenic properties, and some studies have suggested that patients receiving nonionic contrast media are difficult to systemically anticoagulate with intravenous heparin. To investigate the potential effects of nonionic contrast media on systemic anticoagulation during diagnostic cardiac catheterization, pharmacokinetics and in vitro anticoagulant activity following a 3,000 U intravenous heparin bolus were assessed in 12 patients assigned randomly to either an ionic or a nonionic contrast agent. Independent of contrast agent, all patients exhibited biphasic (nonlinear) heparin pharmacokinetics characterized by an initial rapid disappearance phase, followed by a second slower phase. Each patient achieved a therapeutic plasma heparin concentration (greater than or equal to 0.2 U/ml) within 10 min of receiving the bolus, and maintained this level throughout the procedure. Heparin anticoagulant activity, as estimated by a standard activated partial thromboplastin time (APTT) was not affected differently by nonionic as compared with ionic contrast media (p greater than 0.05). Each patient rapidly achieved a level of systemic anticoagulation commonly considered therapeutic (APTT greater than or equal to 1.5 times the control), and maintained this level throughout the procedure. In both groups, APTT correlated directly with plasma heparin concentration (r = 0.95; p less than 0.0001), and inversely with the total amount of contrast media used during the procedure (r = -0.25; p = 0.01). Plasma heparin concentration did not correlate with total contrast media (r = -0.16; p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)