Evaluation of the effects of noniodinized and iodinized ionic contrast media and gadoteric acid in acute necrotizing pancreatitis: experimental study in rabbits.

OBJECTIVE: To evaluate the effects of iodine contrast media and gadoteric acid in acute necrotizing pancreatitis. METHODS: Fifty rabbits were distributed in 5 groups: 10 rabbits were assigned in the control group (group 5) and 40 rabbits were assigned in the pancreatitis group, wherein acute necrotizing pancreatitis was induced through retrograde injection of 5% sodium taurocholate (1 mL/kg weight) in the main pancreatic duct. After 3 hours, they were randomized to receive endovenous iodinized nonionic contrast medium (group 1), iodinized ionic contrast medium (group 2), gadoteric acid (group 3), and physiological serum at 0.9% (group 4). Six hours after induction of pancreatitis, these animals were reoperated. During surgery, pancreatic tissue flow through laser Doppler, hematometric values, biochemistry, and histopathology analysis by hematoxylin and eosin were done. Statistical analysis using Kruskal-Wallis, Fisher-Freeman-Halton, and parametric t tests was performed. RESULTS: There was statistical significance when comparing tissue flow before and after induction of pancreatitis (P < 0.0001). Ionic and nonionic contrast media and gadoteric acid did not increase the grade of pancreatic necrosis (P > 0.05). CONCLUSIONS: Ionic and nonionic contrast media and gadoteric acid did not produce adverse effects in the present model of acute necrotizing pancreatitis.

Effect on bone induction of using contrast media to reconstitute recombinant human bone morphogenetic protein-2 in an ectopic model in rats.

OBJECT: In this study the authors tested the osteoinductive potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) when combined with each of three commercially available contrast media (Conray, Omniscan, and Optiray). METHODS: Initial in vitro and cadaver tests verified the feasibility of using contrast media to visualize absorbable collagen sponge implants containing rhBMP-2 on fluoroscopic radiographic images. For the feasibility studies, lyophilized rhBMP-2 was prepared for injection by reconstitution with contrast media instead of sterile water. For the in vivo study, samples of an rhBMP-2 stock solution were diluted to 0.1 mg/ml by using three contrast media. In each sample, the final solution consisted of 97% contrast medium by volume. Recombinant human bone morphogenetic protein-2 diluted with sterile water for injection was used as a positive control. The rhBMP-2 solutions were applied to 0.5-cm3 collagen sponges and implanted subcutaneously on the thoracic cavity of athymic rats. At 4 weeks, the rats were killed, and the implants were removed. The explants were graded for degree of bone formation by using manual palpation and radiographic and histological assessments. CONCLUSIONS: By all methods of evaluation used, rhBMP-2 diluted with Omniscan was equivalent to rhBMP-2 diluted with sterile water in inducing bone formation. Both Conray and Optiray were shown to inhibit the osteoinductive potential of rhBMP-2.

Effect of contrast material on transitional cell carcinoma viability.

OBJECTIVES: To assess the effects of contrast material on the viability of transitional cell carcinoma (TCC) cells and the ability of such cells to attach to a recipient bed, because seeding of TCC into the upper urinary tract is a possibility during retrograde pyelography or percutaneous procedures. METHODS: Primary cultures of TCC cells were established and placed in either quarter, half, or full-strength contrast for 10 minutes or one-quarter strength contrast for 10, 30, and 60 minutes. Cells were then removed from the contrast agent, resuspended in urothelium-specific media, and incubated for 5 days, after which the cells were counted. RESULTS: A pronounced decrease in cell viability was observed with increasing exposure time and contrast material concentration. Cells incubated for 10, 30, and 60 minutes with contrast yielded an average of 79%, 60%, and 12% of the control group growth, respectively (P <0.001). Likewise, plates incubated with quarter, half, and full-strength contrast yielded 79%, 27%, and 10% of the control group growth, respectively (P <0.001). The difference in the response of low-grade superficial and high-grade invasive bladder tumors was not statistically significant. CONCLUSIONS: TCC cells that have been exposed to dilute contrast material for a short period are able to attach and grow on an adequate recipient bed. However, increasing the contrast concentration and/or the exposure time appears to decrease the viability and adherence of the TCC cells.

Effect of radiographic contrast agents on leukocyte metabolic response.

BACKGROUND: The use of radiographic contrast media in the setting of possible bowel ischemia and potential perforation is known to carry a risk of morbidity and mortality. However, studies of the effect of available contrast media on host immunological defense mechanisms are lacking. We have examined the effect of barium and of two water-soluble contrast agents of differing iodine concentration and osmolality, Conray 30 and Cysto Conray II, on leukocyte phagocytosis. MATERIALS AND METHODS: Blood samples were incubated with the contrast media alone (termed the "resting state"), and in combination with a standard phagocytic challenge (Zymosan polysaccharide extract) and with Staphylococcus epidermidis, Streptococcus faecalis and Escherichia coli, to determine the effect of contrast media upon leukocyte phagocytic response. Incubation with saline was used as control. In the case of barium, the "resting state" and standard challenge experiments were repeated at nine dilutions, ranging from 1:1 to 1:1000. The leukocyte phagocytic response was measured in two ways: CO2 generation (an index of metabolic activity) and chemiluminescence (an index of generation of reactive oxygen species and bacterial killing). RESULTS: Barium, at clinical dilutions, causes a significant increase of baseline "resting state" phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media on bacteria was more complex (although inhibition is minor compared to barium). CONCLUSIONS: Our data demonstrate that barium is a significant activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these data serve to explain the enhanced adverse effect of barium in cases of fecal peritonitis.

The differential effect of contrast agents on endothelial cell and smooth muscle cell growth in vitro.

PURPOSE: This study was designed to evaluate the effects of ionic and nonionic contrast agents on endothelial cell (EC) and smooth muscle cell (SMC) proliferation, and to determine the role of osmolality as the etiology of these effects. METHODS: Cultured bovine aorta EC and SMC were exposed to ionic (iothalamate meglumine) or nonionic (ioversol or iopamidol) contrast, or varying osmolar solutions of mannitol, for periods of 1, 3, 5, 10, or 20 minutes. Cells were then incubated in growth media at 37 degrees C and proliferation and structure were assessed 1, 3, 5, and 7 days later. RESULTS: Both EC and SMC showed decreased proliferation after brief exposure to both ionic and nonionic contrast. Proliferation was markedly decreased at 24 hours after exposure, and began to recover by day 3 after exposure. EC showed a significant decrease up to 7 days after exposure to ionic contrast (p < 0.03), whereas SMC showed a significant decrease up to 7 days after exposure to nonionic contrast (p < 0.001). The decrease in proliferation was directly dependent on the length of exposure to the contrast and the concentration of the contrast. EC proliferation decreased in proportion to increasing osmolality of the test solution (p < 0.05). SMC proliferation did not show a decrease proportional to osmolality. No change was observed in cell viability as assessed by LDH activity studies. After contrast exposure, bare areas with no cells present were noted in the previously confluent EC and SMC culture wells. Cell structure was altered immediately after exposure to contrast, with normal structure recovered by 24 hours after exposure. CONCLUSION: This study demonstrates that brief exposure to contrast agents injures EC and SMC, altering their structure and decreasing proliferation for up to 7 days in vitro. This response is both dose and time dependent. EC are more severely affected by ionic contrast, and SMC are more severely affected by nonionic contrast. EC injury appears to be mediated by the osmolar effect of the contrast, but the effects of contrast on SMC seem to be due to a different mechanism.

Effects of ionic and nonionic contrast media on clot structure, platelet function and thrombolysis mediated by tissue plasminogen activator in plasma clots.

Various radiographic contrast agents have anticoagulant or prothrombotic properties. Ionic agents are reported to have greater antithrombotic potential while nonionic agents are considered more thrombogenic. Some agents after fibrin structure and bind to platelets in purified systems. This study compared the effects of iohexol, a nonionic agent, and iothalamate, an ionic agent, on fibrin assembly, clot structure, platelet function and clot dissolution in plasma. Plasma gels containing increasing concentrations of iothalamate were composed of thinner fibers with decreased fiber mass/length ratios (mu) and reduced gel turbidity. Such clots were more rigid and more resistant to fibrinolysis induced by tissue plasminogen activator (tPA). Gel elastic modula increased from 10,000 to 27,000 dyn/cm2 as iothalamate concentration increased from 0 to 20 mM. 50% lysis time increased from 800 to 1,250 s with the addition of 10 mM iothalamate. At 20 mM, iothalamate had no effect on ADP-induced platelet aggregation but prolonged the lag phase seen with collagen-induced aggregation. Platelet force development increased from 15,300 to 20,400 dyn with 20 mM iothalamate. The effect of iohexol were similar. Gel optical density dropped from 0.50 to 0.32, mu fell from 3.3 to 2.2 x 10(13) D/cm, and elastic modulus rose from 11,000 to 24,000 dyn/cm2 as iohexol concentration was increased from 0 to 20 mM. Clots formed in the presence of 60 mM iohexol and tPA did not dissolve in 72 h while control clot 50% lysis time was 450 s. At concentrations > or = 40 mM, iohexol completely blocked collagen-induced platelet aggregation. Platelet force development increased from 7,660 to 19,600 with 40 mM iohexol. Contrast media possess profound fibrin-altering activities in plasma. Fibrin formed in the presence of some agents may be significantly more resistant to fibrinolysis.

[Contrast medium-induced expansion of circulating blood volume: Comparison between nonionic and ionic contrast media].

We assessed whether the osmotic expansion of circulating blood volume (CBV) induced by nonionic contrast medium (NCM) is less than that induced by ionic contrast medium (ICM). Iohexol (Io) (NCM: 795 mO sm/kg H2O), 1.28 g iodine/kg, was injected intravenously into 5 mongrel dogs and blood samples were drawn at certain times. One week later, meglumine iothalamate (MI) (ICM: 1470 mOsm/kgH2O), 1.28 g iodine/kg, was injected into the same dogs. Another 5 dogs received MI first and Io one week later. Colloid oncotic pressure (COP) of the blood samples was measured by a needle osmometer, and changes in CBV were calculated from the COP values. The injection of Io or MI resulted in an immediate decrease in COP, and an increase in CBV at 1 min. MI induced significantly more severe and longlasting changes in COP and CBV than Io. Neither MI nor Io modified COP when they were added to the control blood samples. Thus, although NCM considerably expanded CBV, the magnitude of expansion induced by NCM was less than that induced by ICM. This may explain one of the reasons why NCM causes fewer adverse reactions than ICM.

Hemodynamic function in dogs with chronic obstructive jaundice: effects of radiocontrast medium.

Chronic obstruction of the biliary tract alters circulatory function. The effects of radiocontrast medium (iothalamate meglumine) on systemic and renal hemodynamics were studied in normal dogs and dogs with chronic common bile duct ligation (CBDL). After intravenous injection of radiocontrast, cardiac output and stroke volume were not altered in normal and CBDL dogs; arterial pressure was stable in normal dogs but decreased significantly in CBDL dogs and was accompanied by reduced systemic vascular resistance. In normal and CBDL dogs the renal hemodynamic responses to radiocontrast medium were characterized by initial vasoconstriction (independent of renal renin release) and later vasodilation. This vasodilatation in CBDL dogs was particularly striking as it occurred despite reduced renal perfusion pressure and the augmented renin-angiotensin system. Inhibition of prostaglandin synthesis with indomethacin in CBDL dogs abolished both the hypotensive and the renal vasodilator responses to radiocontrast medium. We conclude that enhanced prostaglandin activity contributes to the labile hemodynamic function noted in obstructive jaundice.

The effects of contrast dye on bacterial growth: an in vitro model.

We devised an in vitro model to examine the effects of Conray 60 contrast dye on microorganisms commonly found in septic arthritis. Using 42 culture plates in aerobic and anaerobic environments, we found no adverse effect on bacterial growth using 30, 7.5, 3.75, and 1.875% concentrations of Conray 60 contrast dye on cultures of Staphylococcus aureus, Hemophilus influenza, and Streptococcus pneumonia.

Myocardial contrast echocardiography: cardiovascular effects of the contrast medium SHU 454 in dogs.

SHU 454 (Schering AG, Berlin, Federal Republic of Germany) is a new contrast agent that releases microbubbles with a median diameter of 3 microns into the circulation. During echocardiography, it permits visualization of myocardial blood flow (MBF) when given by intracoronary or aortic root injections. Its hemodynamic effects were investigated in anesthetized dogs with a view to application in humans. Cardiac effects were studied after intracoronary injections of 1 mL of SHU 454 (100 mg/mL). Twenty seconds after injection, MBF increased 35% and coronary vascular resistance decreased accordingly. The increase in MBF was not seen when the coronary bed was maximally dilated with intravenous dipyridamole. Peripheral effects were evaluated after 5 mL of SHU 454 (200 mg/mL) was injected into the aortic root, which gave the same myocardial echo contrast. Aortic pressure decreased 5%, and heart rate and dP/dt increased. To evaluate the effects of hypertonicity, SHU 454 was compared with five radiocontrast media and glucose. Its effects on MBF were similar to those of radiologic contrast media on an equal volume basis. Only 1 mL of intracoronary SHU 454, however, was required for myocardial contrast enhancement. The results suggest that visualization of the myocardium using SHU 454 or similar compounds for contrast echocardiography is a viable prospect.

Muscular and CNS effects of carotid artery administration of contrast media in rabbits.

Facial muscle twitching during intracarotid injections of nonionic contrast media has been observed in rabbits. To investigate the cause of this reaction, cortical EEG and facial EMG recordings were made from rabbits receiving selective internal and external carotid artery injections of control solutions (normal saline, mannitol), an ionic contrast medium (meglumine iothalamate), and three nonionic contrast media (iohexol, iopromide, and iotrolan). Internal carotid artery injections with all contrast media, both ionic and nonionic, produced ipsilateral EEG changes in 24 of 28 animals; however, ipsilateral EMG changes and visible twitching were observed only in animals injected with nonionic contrast media. Internal carotid artery injections with control ionic and nonionic solutions (physiological saline and mannitol, respectively) produced no EEG changes in any animals. Mannitol produced only ipsilateral EMG changes and visible twitching in most animals. The severity of the reaction to mannitol was generally less than that to the nonionic contrast media, and this difference was statistically significant when comparing mannitol with iohexol and iotrolan but not with iopromide. External carotid artery injections with nonionic solutions (contrast media and mannitol) produced significantly more severe ipsilateral EMG changes and visible twitching than were recorded with the internal carotid artery injections. Ionic solutions (contrast media and saline) had no effect. EEG changes were not observed after external carotid artery injection of any solution, with the exception of two of the seven animals injected with iotrolan. Angiography demonstrated retrograde filling of the external carotid arterial system from internal carotid artery injection via functioning orbital anastamoses. In contrast, internal carotid arterial vessels were not seen angiographically after external carotid artery injection.(ABSTRACT TRUNCATED AT 250 WORDS)

[Electronystagmographic evaluation of changes in vestibular reactions after administration of diverse substances into cerebral ventricles]. / Elektronistagmograficheskaia otsenka izmeneniia vestibuliarnykh reaktsii posle vvedeniia v zheludochki mozga razlichnykh veshchestv.

Vestibulo-oculomotor reflexes (nystagmus) were recorded by the method of electronystagmography in 33 neurosurgical patients before and after ventriculography. Cerebral ventricles were examined using water soluble compounds (conray, dimeriks, amipaque) in 18 patients or water soluble compounds combined with majodil emulsion in 15 patients. Ventriculography by means of water soluble compounds led to insignificant changes in nystagmic parameters while that by means of X-ray contrasting mixtures caused a frequent and noticeable enhancement of stem vestibular reactions as related to all nystagmic parameters and a significant increase of vestibulo-autonomic reactions.

Estudo comparativo entre um novo meio de contraste de baixa concentraçäo em sódio), AG 64-03 (Ioxitalamato de meglumina e sódio) e o Iotalamato de meglumina e sódio) / Comparative study between a new contrast media of low sodium concentration, AG 64-03 (meglumine ioxithalamate and sodium) and iothalamate meglumine and sodium

Foram analisadas as alteraçöes hemodinâmicas, eletrocardiográficas e reaçöes sistêmicas, em 30 pacientes estudados pela cinecoronariografia e ventriculografia esquerda, com o objetivo de comparar os efeitos de dois meios de contraste. Aleatoriamente, foram empregados os meios de contraste AG 64-03 e o iotalamato de meglumina e sódio, em 18 e 12 pacientes (grupo A e B), respectivamente. A freqüência cardíaca (FC) e as pressöes sistólica, diastólica final e média do ventrículo (VE) (PSVE, PD2 VE e PMVE) foram registradas antes e após a ventriculografia esquerda e ao final da cinecoronariografia. Observou-se, após a ventriculografia, maior aumento da FC no grupo B (p < 0,01) e maior aumento da PSVE, após a coronariografia (p < 0,001). As outras variáveis näo apresentaram diferenças significativas. O tempo de recuperaçäo do eletrocardiograma (ECG), no grupo A foi de 14 + ou - 3s, contra 28 + ou - 10s no grupo B (p <0,001). Durante a injeçäo de contraste na coronária esquerda (CE), o grupo B apresentou uma incidência de 40% de arritmias no ECG, enquanto o grupo A nada registrou. Os efeitos colaterais sistêmicos foram discretos em ambos os grupos. Visto que as maiores diferenças dos efeitos colaterais destes dois meios de contraste säo verificadas no ECG, conclui-se que a menor viscosidade (7,5/9,0 cP) e a menor concentraçäo de sal de sódio (9,66/26,00%) do contraste AG 64-03 devem ser os fatores responsáveis pela diminuiçäo de tais efeitos indesejáveis e que o contraste AG 64-03 oferece mais segu

Effects of intracarotid ionic and non-ionic contrast material on the blood-brain barrier in a rabbit model.

A rabbit model was used to assess the effects of intracarotid injections of ionic monomer (meglumine iothalamate), non-ionic monomer (iohexol, iopromide), and non-ionic dimer (iotrol) contrast materials on the blood-brain barrier. The degree of blood-brain barrier damage was assessed qualitatively using Evans' blue dye, and quantitatively by calculating the difference in pertechnetate uptake between injected and non-injected hemispheres. The results showed that the non-ionic dimer, iotrol, had the least effect on the blood-brain barrier, and that although iopromide and iohexol produced greater damage than iotrol, the ionic compound, meglumine iothalamate, caused the greatest disruption to the blood-brain barrier. The implications of these findings are discussed.

Effect of a radiographic contrast agent on renal function in the rat. Comparison with equiosmolar mannitol.

The renal effects of the radiographic contrast agent meglumine iothalamate (Conray; C) were evaluated in rats. C produced a 42% fall in glomerular filtration rate (p less than 0.05) and a 44% fall in effective renal plasma flow (p less than 0.05). The effects of C were blunted by both acute and chronic volume expansion. Equiosmolar mannitol produced similar hemodynamic responses as C. The fractional excretions of sodium and potassium were similar in rats given C or mannitol. The renal effects of C appear to be due to its hypertonicity. These effects may be modified by volume expansion.

Comparative neurotoxicity of angiographic contrast media.

The neurotoxic effects in cerebral angiography of three iodinated ionic contrast media, nonionic iopamidol, 25% mannitol, and saline controls were compared in 25 rabbits. Diatrizoate sodium meglumine was the most toxic agent, followed by diatrizoate and meglumine, iothalamate meglumine, and mannitol in terms of blood-brain barrier (BBB) disruption and coupled perfusion decline. HIPDm distribution was more sensitive than trypan blue extravasation for monitoring brain dysfunction. Iopamidol and saline controls exhibited no visual BBB breakdown or alteration in regional uptake of I-125 HIPDm, confirming the safety of nonionic iopamidol as compared with presently used ionic contrast media.