RESUMEN
Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect subjects in the disorder of CM-induced nephropathy. Our previous work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)-related adaptive unfolding protein response (UPR) activators. Glucose-regulated protein 78 (GRP78)/eukaryotic initiation factor 2α (eIF2α)-related pathways play a protective role during the urografin (an ionic CM)-induced renal tubular injury. However, the involvement of ER stress-related apoptotic signals in the urografin-induced renal tubular cell injury remains unclear. Here, we examined by the in vivo and in vitro experiments to explore whether ER stress-regulated pro-apoptotic activators participate in urografin-induced renal injury. Urografin induced renal tubular dilation, tubular cells detachment, and necrosis in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic transcriptional factors, and kidney injury marker-1 (kim-1) were also conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of normal rat kidney (NRK)-52E tubular cells with urografin augmented the expressions of activating transcription factor-6 (ATF-6), C/EBP homologous protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1 signals. Urografin-induced renal tubular cell apoptosis was not reversed by the inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be partially reversed by the inhibitor of caspase-12. Taken together, the present results and our previous findings suggest that exposure of CM/urografin activates the ER stress-regulated survival- and apoptosis-related signaling pathways in renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially involved in the urografin-induced nephropathy.
Asunto(s)
Apoptosis/fisiología , Caspasa 12/metabolismo , Medios de Contraste/toxicidad , Diatrizoato de Meglumina/toxicidad , Túbulos Renales/enzimología , Túbulos Renales/lesiones , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/enzimología , Túbulos Renales/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
Contrast media (CM) are frequently used in diagnostic radiology and in radiotherapy as a diagnostic tool and in treatment planning. Previous studies have demonstrated that these compounds induce chromosomal aberrations. This study evaluates the mutagenic effects induced by the contrast medium Urografina® 292 (meglumine amidotrizoate and sodium-ionic dimmer) in bone marrow cells (BMC) of mice in vivo. Micronuclei assay was performed in BMC of CF-1 mice injected with CM 1.5 and 3.0 mL/kg intravenous doses and 1.0, 2.0, 3.0 mL/kg intraperitoneal doses. The animals were beheaded 24 h after treatment by cervical dislocation, and femur BMC from each animal were used in the micronucleus test. The group treated with the highest intravenous injection of Urografina® 292 (3.0 mL/kg) presented an increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in relation at the control group (P<0.05). The results obtained after intraperitoneal administration of CM showed that all doses (1.0 mL/kg, 2.0 mL/kg and 3.0 mL/kg) increased the frequency of MNPCEs, being significantly different from the negative control (P< 0.01). The present results suggest that iodinated contrast media Urografina® 292 may cause a significant increase of cytogenetic damage in bone marrow cells of mice.
Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Aberraciones Cromosómicas/inducido químicamente , Medios de Contraste/toxicidad , Diatrizoato de Meglumina/toxicidad , Animales , Medios de Contraste/administración & dosificación , Diatrizoato de Meglumina/administración & dosificación , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos , Pruebas de Micronúcleos/métodosRESUMEN
OBJECTIVE: The objective of this study is to evaluate the effect and mechanism of aging on iodinated-contrast-media-induced nephropathy in male rats. METHODS: Twenty-four healthy male rats were initially divided into 12-month-old and 24-month-old age groups (adult and older age groups, respectively; n = 12/group); subsequently, each age group was randomly divided into saline control (NS) and contrast media (CM) groups (n = 6/group). CM (76% diatrizoate, 10 mL/kg b.w.) was given through the caudal vein. Urinary creatinine (Ucr) and serum creatinine (Scr) were detected by an automatic biochemical analyzer. The activities of renal malondialdehyde (MDA), superoxide dismutase (SOD), angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and reduced form of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) were determined by spectrophotometric assays with commercially available kits according to the manufacturers' protocols. Renal histological changes were observed by hematoxylin and eosin staining and scored semiquantitatively. RESULTS: In diatrizoate-injected aged rats, Scr, the activities of ACE, Ang II, MDA, and NADPH oxidase in renal tissues were significantly increased (p < 0.01). The histologic scores were higher in the aged animals with CM treatment than those of control or adult rats (p < 0.01). There was an increasing trend but no significant statistical difference in renal ACE, Ang II, MDA, and NADPH oxidase or histologic scores in adult CM-injected rats compared with control animals (p > 0.05). CONCLUSIONS: Older age is an aggravating factor of iodinated-contrast-media-induced nephropathy in male rats. Oxidative stress and the renin-angiotensin system (RAS) may play an important role in nephrotoxicity induced by iodinated contrast media, especially in aged male rats.
Asunto(s)
Envejecimiento/efectos de los fármacos , Medios de Contraste/toxicidad , Diatrizoato de Meglumina/toxicidad , Enfermedades Renales/inducido químicamente , Riñón/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Sistema Renina-Angiotensina/fisiología , Angiotensina II/metabolismo , Animales , Modelos Animales de Enfermedad , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Masculino , Malondialdehído/metabolismo , NADP/metabolismo , Ratas , Ratas Sprague-Dawley , Sistema Renina-Angiotensina/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
Diabetes mellitus is an independent risk factor for renal impairment in patients exposed to contrast media. It doubles the risk and decreases survival rate of contrast induced nephropathy (CIN). Sulforaphane has antioxidant properties via Nrf2 activation. The interaction of diabetes and/or sulforaphane with contrast media on Nrf2 regulation is not yet understood. Herein, diabetes was induced by a single intra-peritoneal injection of streptozotocin. Animals were then divided into five groups; control non-diabetic group; diabetic group; diabetic/sulforaphane group; diabetic/CIN group; diabetic/CIN/sulforaphane group. Animals were assessed 24â¯h after CIN induction. Sulforaphane improved the impaired nephrotoxicity parameters, histopathological features, and oxidative stress markers induced by contrast media (meglumine diatrizoate) in diabetic rats. Immunofluorescence detection revealed increased Nrf2 expression in kidney sections after sulforaphane pretreatment. Moreover, gene expression of Nrf2 and HO-1 were up-regulated, while IL-6 and caspase3 were down-regulated in kidney tissues of animals pretreated with sulforaphane. In NRK-52E cells, sulforaphane pretreatment significantly ameliorated the cytotoxicity of meglumine diatrizoate. However, silencing Nrf2 using small interfering RNA (siRNA) abolished the cytoprotective effects of sulforaphane. Collectively, the results of this study suggest that Nrf2/HO-1 pathway has a protective role against CIN and support the clinical implication of Nrf2 activators, such as sulforaphane, in CIN particularly in diabetic patients.
Asunto(s)
Apoptosis/efectos de los fármacos , Medios de Contraste/toxicidad , Daño del ADN/efectos de los fármacos , Diabetes Mellitus Experimental/patología , Diatrizoato de Meglumina/toxicidad , Isotiocianatos/química , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Antioxidantes/química , Línea Celular , Medios de Contraste/química , Diabetes Mellitus Experimental/inducido químicamente , Diatrizoato de Meglumina/química , Regulación de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Masculino , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Factor 2 Relacionado con NF-E2/genética , Nefritis/inducido químicamente , Nefritis/metabolismo , Nefritis/patología , Interferencia de ARN , ARN Interferente Pequeño , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , SulfóxidosRESUMEN
OBJECTIVE: To explore the protective effect of amlodipine on the cytotoxicity induced by contrast media (meglumine diatrizoate) in human kidney cells (HKC). METHODS: An HKC line was used. The experiment was divided into 4 groups: a model group (diatrizoate 111g/L), a prevention group (diatrizoate 111g/L+amlodipine 10(-5)mol/L), an amlodipine control group (amlodipine 10(-5)mol/L), and a culture medium control group (simple none blood serum DMEM-F12 medium). Cytotoxicity induced by meglumine diatrizoate was analysed by methyl thiazolyl tetrazolium (MTT) test, lactate dehydrogenase (LDH) assay, Hochest33258 fluorescence stained cytospins, and flow cytometric DNA analysis. The protein expression of Bax was determined by Western blot, and caspase-3 activity was examined by fluorometric method. RESULTS: In the prevention group, the cell viability increased significantly (P<0.05), LDH levels decreased (P<0.05), and the apoptosis was lower than that of the model group (P<0.05) .Bax protein expression and caspase 3 activity decreased (P<0.05). CONCLUSION: Amlodipine can inhibit the HKC apoptosis and protect the renal tubule cell from injury induced by meglumine diatrizoate.
Asunto(s)
Amlodipino/farmacología , Medios de Contraste/toxicidad , Células Epiteliales/efectos de los fármacos , Túbulos Renales/citología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular , Diatrizoato de Meglumina/toxicidad , Células Epiteliales/citología , Humanos , Túbulos Renales/efectos de los fármacos , Sustancias Protectoras/farmacologíaRESUMEN
Myocardial contrast echocardiography can define in vivo the area at risk for necrosis after coronary occlusion. However, if this technique is to be used, it cannot be intrinsically toxic to the heart or other critical organs. To determine the functional and pathologic effects of contrast echocardiography, six intracoronary, six intrarenal and six intracarotid artery injections of 2 to 6 cc of a commonly employed contrast agent (agitated Renografin-saline solution) were performed in five dogs. A sixth dog served as a sham to assess any deleterious effects of the model preparation. Two-dimensional echocardiographic images and electrocardiograms were recorded during intracoronary injections, and heart rate, blood pressure, left ventricular end-diastolic pressure and rate of rise of left ventricular pressure (dP/dt) were continuously monitored. At 24 hours, echocardiographic and hemodynamic measurements were repeated, the dogs were killed and the heart, brain and kidneys were removed and prepared for light microscopic examination. Quantitative analysis of left ventricular wall motion was performed on control, peak contrast, post-contrast and 24 hour studies. With each intracoronary injection, there were transient decreases in blood pressure (p = 0.05 versus control) and increases in left ventricular end-diastolic pressure (p = 0.04 versus control). These were associated with depression of wall motion in contrast-enhanced regions (p = 0.01 versus control) and ST-T segment changes on the electrocardiogram. No significant change in heart rate or left ventricular dP/dt was noted. All variables normalized with the clearance of the contrast effect and remained normal to 24 hours. Light microscopic examination revealed no myocardial or cerebral changes attributable to the contrast agent injections.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Encéfalo/efectos de los fármacos , Diatrizoato de Meglumina/toxicidad , Diatrizoato/análogos & derivados , Diatrizoato/toxicidad , Ecocardiografía/métodos , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Encéfalo/patología , Perros , Electrocardiografía , Frecuencia Cardíaca/efectos de los fármacos , Riñón/patología , Contracción Miocárdica/efectos de los fármacos , Miocardio/patología , Solución Salina Hipertónica/toxicidadRESUMEN
In this study, silica coated Au nanospheres (Au@SiO2) were prepared by a reverse microemulsion method; subsequently, a layer of fluorescent quantum dots (QDs) were adsorbed onto it and then it was coated with silica again. After modifying with PVP, the composite silica coated gold nanosphere and quantum dots nanoparticle (Au@SiO2-QDs/SiO2-PVP) was obtained. This composite structure contained Au and QDs, and it could be used for contrast-enhanced X-ray CT imaging and fluorescence imaging. Characterization showed that the composite nanoparticle had good dispersity, a high fluorescence intensity and a good effect of X-ray absorption, and it was suitable for using as a bimodal imaging probe.
Asunto(s)
Colorantes Fluorescentes/química , Oro/química , Nanopartículas/química , Puntos Cuánticos/química , Dióxido de Silicio/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Medios de Contraste/química , Medios de Contraste/toxicidad , Diatrizoato de Meglumina/química , Diatrizoato de Meglumina/toxicidad , Emulsiones , Colorantes Fluorescentes/toxicidad , Oro/toxicidad , Ratones , Nanopartículas/toxicidad , Nanopartículas/ultraestructura , Imagen Óptica , Povidona/química , Puntos Cuánticos/toxicidad , Dióxido de Silicio/toxicidad , Espectroscopía Infrarroja por Transformada de Fourier , Tomografía Computarizada por Rayos XRESUMEN
To investigate whether tauroursodeoxycholic acid (TUDCA) could attenuate contrast media (CM)-induced renal tubular cell apoptosis by inhibiting endoplasmic reticulum stress (ERS), we exposed HK-2 cells to increasing doses of meglumine diatrizoate (20, 40, and 80 mg I/mL) for 2 to 16 hours, with/without TUDCA preconditioning for 24 hours. Cell viability test, Hoechst 33258 staining, and flow cytometry were used to detect meglumine diatrizoate-induced cell apoptosis, while real-time polymerase chain reaction and Western blot analysis were used to measure the expressions of ERS markers of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), and the apoptosis-related marker of caspase 12. Cell apoptosis and messenger RNA (mRNA) expression of GRP78 (P = .005), ATF4 (P = .01), and caspase 12 (P = .001) were significantly higher in the CM 4 hours group than the control as well as the protein expressions. The TUDCA preconditioning reduced the mRNA expression of GRP78, ATF4, and caspase 12 in the CM 4 hours groups (P = .009, .019, and .003, respectively) as well as the protein expression. In conclusion, TUDCA could protect renal tubular cells from meglumine diatrizoate-induced apoptosis by inhibiting ERS.
Asunto(s)
Apoptosis/efectos de los fármacos , Medios de Contraste/toxicidad , Diatrizoato de Meglumina/toxicidad , Estrés del Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Túbulos Renales Proximales/efectos de los fármacos , Sustancias Protectoras/farmacología , Ácido Tauroquenodesoxicólico/farmacología , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo , Caspasa 12/genética , Caspasa 12/metabolismo , Línea Celular , Citoprotección , Relación Dosis-Respuesta a Droga , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/patología , Chaperón BiP del Retículo Endoplásmico , Células Epiteliales/metabolismo , Células Epiteliales/patología , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , ARN Mensajero/metabolismo , Factores de TiempoRESUMEN
Coronary angiography with Renografin-76 (meglumine sodium diatrizoate, Squibb) lowers the ventricular fibrillation threshold (VFT) significantly and in a dose-dependent manner. Recently new contrast materials have been synthesized for possible angiographic use. We compared the fibrillatory propensities of Hexabrix (meglumine sodium ioxaglate, Guerbet), a monacid dimer; Exypaque (Nyegaard; U.S. iohexol, Winthrop), a new nonionic agent; and Amipaque (metrizamide, Winthrop), an older nonionic agent, to Renografin-76 in anesthetized dogs. The VFT following subselective left circumflex artery injections of 370-mg I and 740-mg I doses of each agent was compared to the control (no injection) threshold in 115 paired experiments in 25 dogs. At the low dose, the VFT for Renografin was significantly lower (61.8 +/- 2.3% of control threshold) than that of Hexabrix or Exypaque (69.3 +/- 2.1%, respectively; P less than 0.05). At the higher dose, the differences were more pronounced among Renografin, Hexabrix, and Exypaque (32.4 +/- 1.4%, 65.7 +/- 2.6%, and 59.2 +/- 2.4%, respectively; P less than 0.001). No statistical difference was detected between the latter two agents at these doses in nonischemic dogs. Amipaque was also less fibrillatory than Renografin and equivalent to the other two agents. These newer agents appear to offer enhanced safety for use in angiographic studies in the heart.
Asunto(s)
Angiografía , Medios de Contraste/toxicidad , Angiografía Coronaria , Fibrilación Ventricular/inducido químicamente , Animales , Diatrizoato de Meglumina/toxicidad , Perros , Relación Dosis-Respuesta a Droga , Femenino , Yohexol , Ácido Yoxáglico , Masculino , Metrizamida/toxicidad , Ácidos Triyodobenzoicos/toxicidadRESUMEN
Electrocardiographic changes induced by ionic contrast media can cause complications during coronary angiography. A conduction delay through various parts of the heart is one factor in the genesis of asystole or ventricular fibrillation. Hypaque-76 (H76) and Renografin-76 (R76) are nearly identical ionic contrast media except that R76 binds more calcium than H76 because of the presence of sodium citrate and EDTA in R76. To determine whether the calcium binding additives in ionic contrast media contribute to the cardiac conduction abnormalities, we examined conduction time through the atrioventricular (AV) nodal tissue (via bipolar His bundle electrograms) and through the distal part of the conduction system (recording the QRS complex from the ECG) during coronary angiography. We injected 10 mL of H76 and R76 in 19 closed chest dogs in a blinded, randomized fashion during coronary angiography. The effects of H76 and R76 on heart rate, AH interval, HV interval, V interval and PR interval, and QRS complex duration were recorded. In 14 nonatrial pacing dogs, compared with H76, R76 produced a greater increase in the AV interval (32.9 +/- 6 milliseconds vs 12.4 +/- 2 milliseconds, P less than .01) and the PR interval (29.6 +/- 6 milliseconds vs 11.9 +/- 4 milliseconds, P less than .02). Additionally, the heart rate decreased 13.9 +/- 3.5 beats/minute from control with R76 compared with a decrease of 4.2 +/- 2.6 beats/minute from control with H76 (P less than .05). There was no significant difference between the prolongation of the HV interval and V interval, or QRS complex duration generated by R76 and H76.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Medios de Contraste/toxicidad , Angiografía Coronaria , Diatrizoato de Meglumina/toxicidad , Diatrizoato/toxicidad , Sistema de Conducción Cardíaco/efectos de los fármacos , Angiografía , Animales , Ensayos Clínicos como Asunto , Perros , Combinación de Medicamentos/toxicidad , Femenino , Masculino , Distribución AleatoriaRESUMEN
Large doses of an ionic contrast medium (CM) can disrupt the blood brain barrier (BBB) osmotically. Acute hypertension (HT) also is known to open the BBB. We tested the hypothesis that these two factors potentiate each other in a rat model. Adult male Wistar rats, anesthetized with pentobarbital, underwent tracheostomy. An external carotid artery catheter was placed so that it opened into the patent common carotid artery; arterial blood pressure was recorded continuously. Of three groups of animals, two (HT) groups received metaraminol to elevate and maintain blood pressure in the range of 165 to 190 mm Hg. The third (normotensive) group received an equivalent volume of saline. Five minutes after injection of Evan's blue, either sodium/meglumine diatrizoate or saline was infused into the carotid cannula (2 mL in 30 seconds). Twenty minutes later the cardiovascular system was flushed with saline, and the brain was removed, frozen, and sectioned for gross and histofluorescent microscopic examination of BBB opening. The carotid injection of CM at a concentration of 1000 mosm/kg water did not produce gross evidence of BBB opening in the normotensive group. Similarly, hypertension at levels below 190 mm Hg did not produce gross evidence of opening in the carotid saline group. However, the combination of carotid CM and HT produced significant BBB opening. These results suggest that the risk factor of acute HT potentiates CM-induced BBB opening.
Asunto(s)
Barrera Hematoencefálica/efectos de los fármacos , Diatrizoato de Meglumina/toxicidad , Hipertensión/fisiopatología , Animales , Hipertensión/inducido químicamente , Masculino , Metaraminol , Ratas , Ratas Endogámicas , Factores de RiesgoRESUMEN
Contrast media occasionally produce ventricular fibrillation during coronary angiography. We compared the fibrillatory propensity of the conventional ionic contrast medium, Hypaque-76 (H76) to the low osmolar ionic dimer Hexabrix (HB) and to the nonionic agent Omnipaque (OM) in 20 open chest anesthetized dogs. Intracoronary injection of 6 mL of contrast medium produced spontaneous ventricular fibrillation in four of ten dogs with H76, compared with two of ten with HB, and zero of ten with OM (P = .07). The induction of two premature beats by programmed stimulation of the myocardium during injection of 4 mL of contrast medium produced ventricular fibrillation in ten of ten dogs with H76, compared with three of ten with HB, and zero of ten with OM (P less than .001). Both H76 and HB produced ventricular fibrillation in ten of ten dogs when three premature beats were induced, compared with two of ten dogs with OM (P less than .001). Four mL H76 produced a 109 +/- 18 msec increase in the QT interval, compared with an 82 +/- 17 msec increase with HB, and a 45 +/- 12 msec increase with OM. We conclude that both low osmolar HB and OM are less fibrillatory than the conventional ionic medium H76, and that the nonionic medium OM is less fibrillatory than the ionic dimer contrast medium HB.
Asunto(s)
Medios de Contraste/toxicidad , Diatrizoato de Meglumina/toxicidad , Diatrizoato/toxicidad , Yohexol/toxicidad , Ácido Yoxáglico/toxicidad , Fibrilación Ventricular/inducido químicamente , Angiografía , Animales , Angiografía Coronaria , Perros , Combinación de Medicamentos/toxicidad , Femenino , MasculinoRESUMEN
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.
Asunto(s)
Medios de Contraste/toxicidad , Deshidratación/complicaciones , Edema Pulmonar/etiología , Animales , Diatrizoato/toxicidad , Diatrizoato de Meglumina/toxicidad , Combinación de Medicamentos/toxicidad , Yohexol , Masculino , Concentración Osmolar , Edema Pulmonar/inducido químicamente , Ratas , Ratas Endogámicas , Ácidos Triyodobenzoicos/toxicidadRESUMEN
RATIONALE AND OBJECTIVES: In a previous study, intrauterine injection of meglumine-sodium diatrizoate (high osmolar contrast media) during hysterosalpingography was found to induce lengthening of the QTc interval on electrocardiography. To evaluate the relationship between high osmolality and electrocardiographic changes during intrauterine injection, the authors evaluated the effect on QTc of two ionic contrast agents with different osmolality during routine hysterosalpingography. METHODS: Forty-eight women undergoing routine hysterosalpingography were included in the study. Thirty-two women received meglumine-sodium diatrizoate (1500 mOsm/kg) and 16 received meglumine-sodium ioxaglate (600 mOsm/kg). QTc changes were evaluated using a 12 lead computerized electrocardiogram system during all the stages of the procedure. RESULTS: In the meglumine-sodium diatrizoate group, QTc interval was prolonged significantly from 419 +/- 19 msec at baseline to 447 +/- 30 msec during injection of contrast material, P < .001, and returned to baseline values in late phase (416 +/- 18 msec). The meglumine-sodium ioxaglate group showed no change in the QTc interval. CONCLUSION: As the single major difference between the two ionic agents is osmolality, we believe that QTc interval prolongation in the meglumine-sodium diatrizoate group is related to increased osmolality.
Asunto(s)
Diatrizoato de Meglumina/toxicidad , Electrocardiografía , Corazón/efectos de los fármacos , Histerosalpingografía , Ácido Yoxáglico/toxicidad , Adulto , Diatrizoato de Meglumina/administración & dosificación , Femenino , Humanos , Ácido Yoxáglico/administración & dosificación , Concentración Osmolar , ÚteroRESUMEN
We compared the damage resulting from intradermal injection of four commonly used radiographic contrast media in laboratory rats. Sixty percent meglumine diatrizoate (Reno M 60) and ioxaglate (Hexabrix) produced significantly more ulceration and crusting on gross inspection and more necrosis, edema, and hemorrhage on histologic evaluation than iopamidol 300 (Isovue) or 0.9% (normal) saline. Thirty percent meglumine diatrizoate (Reno M Dip) had an intermediate toxicity, resulting in significantly more visible swelling and more microscopically detected hemorrhage than iopamidol or saline, but less ulceration/crusting and necrosis than Reno M 60 and ioxaglate. Since the three contrast agents of similar osmolality produced different degrees of tissue damage, our results suggest that factors other than high osmolality are partially responsible for determining the severity of injuries from extravasated contrast media.
Asunto(s)
Medios de Contraste/toxicidad , Extravasación de Materiales Terapéuticos y Diagnósticos/complicaciones , Enfermedades de la Piel/inducido químicamente , Animales , Diatrizoato de Meglumina/toxicidad , Edema/inducido químicamente , Yopamidol/toxicidad , Ácido Yoxáglico/toxicidad , Masculino , Necrosis , Concentración Osmolar , Ratas , Ratas Endogámicas , Úlcera Cutánea/inducido químicamenteRESUMEN
Although perfluorooctylbromide (PFOB) is known to stimulate macrophages, particulates given intravenously (IV) can inhibit the body's response to infection by blocking the reticuloendothelial system. Since PFOB enhances abscesses on computed tomography (CT), the authors evaluated its safety and efficacy by assessing the mortality and abscess volume in 104 rabbits with intrahepatic abscesses given either PFOB or lactated Ringer's (LR), and by comparing its efficacy to that of 76% meglumine sodium diatrizoate (MSD76). Abscesses were produced by injecting a virulent strain of E. coli into the liver. Two days later, five of the rabbits had died. Of the remaining rabbits, 50 were given 5 g/kg PFOB IV, and 49 were given an equal volume of LR. All rabbits had a CT scan at four and at ten days after infusion. They were killed before the second CT scan. Thirty seconds before being killed, 28 rabbits given LR were given a bolus of 2 ml/kg MSD76 IV. Following CT, rabbits were frozen, sliced, and photographed. Abscess volumes were calculated by digitizing the photographs of the anatomic sections and the CT images. MSD76 enhanced the liver by 105 Hounsfield units (HU) more than the liquefied abscess center. The abscess wall enhanced to the same degree as liver, resulting in nonvisualization of three of six abscesses less than 3 mm in size, and a 30% underestimation of true abscess volume.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Fluorocarburos , Absceso Hepático/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Animales , Medios de Contraste/toxicidad , Diatrizoato de Meglumina/toxicidad , Fluorocarburos/toxicidad , Hidrocarburos Bromados , Absceso Hepático/patología , ConejosRESUMEN
We compared the relative toxicities of standard concentrations of two magnetic resonance imaging (MRI) contrast agents, ionic gadolinium diethylenetriaminepentacetic acid (DTPA) and low-osmolar gadolinium-1, 4, 7 tris (carboxymethyl)-10-(2'-hydroxypropyl)-1, 4, 7, 10 tetra-azacyclododecane (HP-DO3A) with that of the conventional radiographic contrast medium meglumine diatrizoate, when extravasated into the deep dermal tissues of laboratory rats. Gadolinium-DTPA caused moderate necrosis, hemorrhage, and edema which was not statistically different than meglumine diatrizoate. In contrast, gadolinium HP-DO3A was significantly less toxic than meglumine diatrizoate. Additional experience will be needed in order to determine whether these laboratory results will be clinically relevant in humans.
Asunto(s)
Medios de Contraste/toxicidad , Extravasación de Materiales Terapéuticos y Diagnósticos , Gadolinio/toxicidad , Compuestos Heterocíclicos/toxicidad , Imagen por Resonancia Magnética , Compuestos Organometálicos/toxicidad , Ácido Pentético/toxicidad , Animales , Diatrizoato de Meglumina/toxicidad , Gadolinio DTPA , Masculino , Concentración Osmolar , Ratas , Ratas EndogámicasRESUMEN
A rat model was employed to investigate contrast media (CM) induced ultrastructural changes in the vascular endothelium. Ionic contrast materials such as Renografin-76 (diatrizoate meglumine diatrizoate sodium), MD-76 (diatrizoate meglumine diatrizoate sodium), and Angiovist (meglumine diatrizoate) were injected into the femoral vein of anesthetized male Wistar rats (240-260 g) and allowed to circulate. Control animals were similarly injected with equiosmolar sucrose and physiologic saline. The thorax was opened 15 minutes, 1 hour, and 4 hours postinjection and cardiac perfusion performed using Karnovsky's fixative; the thoracic aorta was then surgically removed, and processed for transmission electron microscopy. All CM produced shrinkage in cell cytoplasm and nuclear structures thereby causing distortions in cell morphology. In control tissues, however, no such ultrastructural damages were noted. Within 15 minutes of CM infusion, electron dense granules were seen on the luminal surface of endothelial cells, in pinocytotic vesicles, as well as in the gap junctions between cells. These observations indicate that contrast media intake occurs via vesicular transport, and through the cell junction.
Asunto(s)
Aorta Torácica/efectos de los fármacos , Medios de Contraste/toxicidad , Animales , Aorta Torácica/ultraestructura , Diatrizoato/toxicidad , Diatrizoato de Meglumina/toxicidad , Diglicéridos/toxicidad , Combinación de Medicamentos/toxicidad , Masculino , Microscopía Electrónica , Ratas , Ratas EndogámicasRESUMEN
We studied the hemodynamic side effects of intracoronary injection of contrast media during acute ischemic heart failure by using anesthetized dogs. Induction of failure was performed by microembolization of the area supplied by the left main coronary artery. Six ml of iohexol (Omnipaque) increased contractility during the normal state, while this contrast medium induced no alterations in any of the recorded hemodynamic variables during left ventricular failure. Ioxaglate (Hexabrix) was also well tolerated during the normal state, while sodium-meglumine diatrizoate (Renografin) markedly decreased systolic variables. However, in the failing heart both ioxaglate and diatrizoate resulted in greater reduction in all systolic variables than in the normal heart. We conclude that both ionic contrast media may be harmful in acute ischemic heart failure. Non-ionic iohexol appears safer in this condition.
Asunto(s)
Gasto Cardíaco Bajo/fisiopatología , Medios de Contraste/toxicidad , Diatrizoato de Meglumina/toxicidad , Corazón/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Yohexol/toxicidad , Ácido Yoxáglico/toxicidad , Animales , Perros , Femenino , Corazón/fisiopatología , MasculinoRESUMEN
Severe cutaneous ulceration may occur as a result of contrast media extravasation. We established a definitive animal model for assessing the cutaneous toxicity of commonly employed agents and used this model to evaluate possible antidotes to the effects of contrast media extravasation. The contrast agents studied were: meglumine/sodium diatrizoate 76%, meglumine iothalamate 60% and 43%, meglumine/sodium ioxaglate 60%, iohexol 350, and iopamidol 370, in varying volumes and osmolalities. Hypertonic saline (950 and 1900 mOsm/kg) also was injected. Agents were injected intradermally into BALB/c mice. The higher osmolality agents produced dose-dependent skin ulcerations. The lower osmolality agents failed to produce any skin lesions after the same volume doses. Hypertonic saline produced skin toxicity in a dose-dependent fashion similar to hyperosmolar contrast agents. Three antidotes were tested: hyaluronidase, topical heat, and topical cold. Hyaluronidase significantly reduced skin toxicity when injected immediately following contrast injection. Cold also significantly reduced skin toxicity, while heat caused no improvement.