An Experimental and Finite Element Protocol to Investigate the Transport of Neutral and Charged Solutes across Articular Cartilage.

Osteoarthritis (OA) is a debilitating disease that is associated with degeneration of articular cartilage and subchondral bone. Degeneration of articular cartilage impairs its load-bearing function substantially as it experiences tremendous chemical degradation, i.e. proteoglycan loss and collagen fibril disruption. One promising way to investigate chemical damage mechanisms during OA is to expose the cartilage specimens to an external solute and monitor the diffusion of the molecules. The degree of cartilage damage (i.e. concentration and configuration of essential macromolecules) is associated with collisional energy loss of external solutes while moving across articular cartilage creates different diffusion characteristics compared to healthy cartilage. In this study, we introduce a protocol, which consists of several steps and is based on previously developed experimental micro-Computed Tomography (micro-CT) and finite element modeling. The transport of charged and uncharged iodinated molecules is first recorded using micro-CT, which is followed by applying biphasic-solute and multiphasic finite element models to obtain diffusion coefficients and fixed charge densities across cartilage zones.

The assessment of thrombotic markers utilizing ionic versus non-ionic contrast during coronary angiography and intervention trial.

OBJECTIVE: To determine how two different types of iodinated contrast media (CM), low-osmolar ionic dimer ioxaglate (Hexabrix) and iso-osmolar non-ionic dimer iodixanol (Visipaque), affect multiple indices of hemostasis. BACKGROUND: In vitro models demonstrate differential effects of ionic and non-ionic CM on markers of hemostasis. METHODS: This blinded endpoint trial randomized 100 patients to ioxaglate or iodixanol. The primary endpoint was change in endogenous thrombin potential (ETP) following diagnostic angiography. Secondary endpoints included change in markers of fibrinolysis [tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1)] and platelet aggregation following diagnostic angiography and percutaneous coronary intervention (PCI) with bivalirudin. Data are presented as median [interquartile range]. RESULTS: ETP significantly decreased after diagnostic angiography in both ioxaglate (baseline 1810 nM*minute [1540-2089] to post-angiography 649 nM*minute [314-1347], p < 0.001) and iodixanol groups (baseline 1682 nM*minute [1534-2147] to post-angiography 681 nM*minute [229-1237], p < 0.001), but the decrease was not different between CM (p = 0.70). There was a significant increase in ETP during PCI (n = 45), despite the use of bivalirudin, suggesting a prothrombotic effect of PCI (post-angiography 764 nM*minute [286-1283] to post-PCI 1081 nM*minute [668-1552], p = 0.02). There were no significant differential effects on tPA, PAI-1, and markers of platelet activity. CONCLUSION: There were no significant differential effects between ioxaglate and iodixanol. Both CM led to significant reductions in thrombin generation and no significant effects on fibrinolytic activity or platelet activity, thereby contributing to a favorable antithrombotic milieu. © 2016 Wiley Periodicals, Inc.

Comparison of Iodixanol and Ioxaglate for Coronary Optical Coherence Tomography Imaging.

BACKGROUND: The impact of contrast type on coronary imaging using optical coherence tomography (OCT) has received limited study. We compared OCT imaging obtained using the non-ionic, iso-osmolar iodixanol with the ionic, low-osmolar ioxaglate. METHODS: Twenty-two vessels in 20 patients were imaged twice using manual injection of iodixanol and ioxaglate in random order. OCT images were analyzed at 1 mm intervals to determine lumen area, artifact diameter and area, as well as stent strut coverage and malapposition in OCT pullbacks that included stents. RESULTS: There were no complications related to OCT imaging or to contrast administration. A total of 2184 cross-sections (1092 with iodixanol and 1092 with ioxaglate) were analyzed. Compared with iodixanol, imaging using ioxaglate provided similar mean lumen area (6.21 ± 2.83 mm2 vs 6.27 ± 2.83 mm2; Spearman's rho, 0.982), mean minimum lumen diameter (2.47 ± 0.59 mm vs 2.50 ± 0.58 mm; Spearman's rho, 0.939), and mean maximum lumen diameter (2.99 ± 0.71 mm vs 3.01 ± 0.70 mm; Spearman's rho, 0.964), but lower mean artifact area per cross-section (0.099 ± 0.325 mm2 vs 0.068 ± 0.329 mm2; P<.001). Analyses of 3303 stent struts in 388 cross-sections (194 with iodixanol and 194 with ioxaglate) demonstrated similar strut malapposition rates (11.82% vs 13.90%; P=.10) and strut coverage (41.92% vs 40.33%; P=.35). CONCLUSIONS: Compared with iodixanol, OCT imaging using ioxaglate provided similar lumen and diameter measurements and stent strut characterization, but smaller area of artifact.

Prevention of cartilage dehydration in imaging studies with a customized humidity chamber.

Quantitative three-dimensional imaging methods such as micro-computed tomography (µCT) allow for the rapid and comprehensive evaluation of cartilage and bone in animal models, which can be used for drug development and related research in arthritis. However, when imaging fresh cartilage tissue in air, a common problem is tissue dehydration which causes movement artifact in the resulting images. These artifacts distort scans and can render them unusable, leading to a considerable loss of time and effort with sample preparation and measurement. The sample itself is also irretrievably damaged by the dehydration, often unable to return to its full tissue thickness upon rehydration. Additionally, imaging with ionic contrast agents such as Hexabrix(TM) must be performed in air, otherwise the agent will be washed out if immersed in a liquid. The first goal of this study was to design a customized humidity chamber to maintain cartilage hydration without the need for immersion. Following this, the use of the humidity chamber during a synchrotron radiation-µCT scan was validated and its performance evaluated. Results showed that the loss of fluid film volume is associated with scanning at low humidity (87%), and can be avoided using the humidity chamber. Coupling this technology with advances in synchrotron imaging (e.g., phase contrast imaging) or contrast agents is promising.

Incompatibility of contrast medium and trisodium citrate.

PURPOSE: To test the compatibility of trisodium citrate, a catheter lock solution, with iodinated contrast medium. METHODS: Iohexol, iobitridol, iodixanol, ioxaglate, ioxithalamate, iomeprol, and iopromide were tested. In all tests, 2 ml of contrast medium were mixed with 2 ml of trisodium citrate solution. RESULTS: Iodixanol and ioxaglate provoked a highly viscous gluelike precipitation when mixed with trisodium citrate. A brief transient precipitate was observed with iohexol, iomeprol, and ioxithalamate. Permanent precipitation occurred with iobitridol and iopromide. CONCLUSION: One must be aware of the potential for precipitation when contrast medium is mixed with trisodium citrate solution. Before trisodium citrate solution is injected, the catheter should be thoroughly flushed with saline if a contrast medium has previously been injected through it.

Impact of anticoagulation on ionic and nonionic contrast media effect on thrombogenesis and fibrinolysis: The PEPCIT study.

OBJECTIVES: The effect of ionic low osmolar contrast media (ICM) and nonionic iso-osmolar CM (NICM) on acute thrombotic complications of percutaneous coronary intervention (PCI) is subject to controversies possibly related to a potential interaction with anticoagulation regimens. We sought to compare physical and morphological properties of fibrin clots made in the presence of ioxaglate (ICM), iodixanol (NICM) versus control and to evaluate the effect of four anticoagulants used in PCI. METHODS AND RESULTS: Maximum platelet aggregation (MPA%), maximum elastic modulus (EM, dyne/cm(2) ) fiber density (n/10(-5) /µm(2) ), and lysis front velocity (nm/sec) of fibrin rich clot (FRC) were measured simultaneously using peripheral blood from 12 patients undergoing elective PCI. We compared the effects of adding iodixanol or ioxaglate or saline (control) to blood with enoxaparin, unfractionated heparin, fondaparinux, and bivalirudin. Iodixanol and ioxaglate led to nonsignificant reduction in MPA compared to control (33.6% ± 16.9%, 28.2% ± 18.9%, and 40.7% ± 13.9%, respectively, P = ns). Fibrin formed with iodixanol was stiffer (42.7 ± 41.9, 18.7 ± 3.7, and 15.9 ± 9 dyne/cm(2) , P < 0.01) and displayed more fibrin fibers (1089 ± 175, 260 ± 108, and 456 ± 131 n/10(-5) /µm(2) , respectively, P < 0.01) than with ioxaglate or control. This resulted in a profound reduction in the lysis front velocity (191 ± 95, 261 ± 112, and 360 ± 153 nm/sec). None of the four anticoagulants displayed any significant interaction on the effect of contrast media. CONCLUSIONS: The prothrombogenic effect of iodixanol is related primarily to an increase in fibrin stiffness with subsequent delayed fibrinolysis, something not seen with ioxaglate. Anticoagulation does not appear to have any impact on this fibrin clot abnormalities.

Ionic contrast media induced more apoptosis in diabetic kidney than nonionic contrast media.

BACKGROUND: Contrast-induced nephropathy is a major cause of hospital-acquired acute renal failure, and its risk is significantly increased in patients with diabetes mellitus. This study aimed to examine both the role of apoptosis in low-osmolar contrast media-induced kidney injury in normal and diabetic rats and the difference in the induced kidney injury between ionic and nonionic contrast media. METHODS: Normal and streptozotocin-induced diabetic Wistar rats were administered with ionic low-osmolar ioxaglate, nonionic low-osmolar iopromide or normal saline injection. Apoptosis in kidney tubular cells was determined by the presence of positive terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end-labeling (TUNEL) stain. RESULTS: At 24 hours after administration, both ioxaglate and iopromide injections induced more apoptosis in diabetic (49.7% vs. 25.3% for ioxaglate; 37.7% vs. 25.3% for iopromide; both p<0.001) and normal (36.2% vs. 27.4%, p=0.002, for ioxaglate; 33.6% vs. 27.4%, p=0.029, for iopromide) kidney tubular cells than normal saline injections. Additionally, ioxaglate induced more apoptotic tubular cells in diabetic kidneys than in normal kidneys (p<0.001). Moreover, ioxaglate significantly induced more apoptotic cells than iopromide in diabetic kidneys, but not in normal kidneys (p<0.001, for diabetic rats; p=0.345, for normal rats). CONCLUSION: Ionic low-osmolar contrast media induced more apoptosis in tubular cells in diabetic kidneys than in normal kidneys. Notably, ionic contrast media induced more apoptosis than nonionic contrast media in diabetic kidneys.

Similar inhibition of platelet adhesion, P-selectin expression and plasma coagulation by ioversol, iodixanol and ioxaglate.

Contrast media (CM) are reported to possess both prothrombotic and anticoagulant properties. The mechanisms are not clearly understood, and early reports are contradictory. To study the effects of CM on haemostasis, we analysed the ex vivo effects of ioversol and iodixanol on platelet adhesion and P-selectin expression, and the in vitro effects of ioversol, iodixanol and ioxaglate on platelet adhesion, P-selectin expression and plasma coagulation. A novel enzymatic assay was used to measure platelet adhesion to protein surfaces, and an enzyme-linked immunosorbent assay was used to measure platelet P-selectin surface expression. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were used to measure plasma coagulation. The ex vivo study consisted of blood from 27 outpatients administered ioversol and 9 patients administered iodixanol intravenously. Samples were collected before and 5 min after CM administration. Healthy donors were used for the in vitro studies on the effects of CM. The ex vivo study showed significantly (p<0.05) decreased platelet adhesion and P-selectin expression after administration of ioversol and iodixanol. Adhesion was more affected than P-selectin expression. The in vitro study showed that ioversol, iodixanol and ioxaglate significantly (p<0.05) and dose-dependently (beginning at 3 mg ml(-1)) decreased platelet adhesion and P-selectin expression. APTT and PT were significantly (p<0.01) prolonged at concentrations of 10 mg ml(-1) and 30 mg ml(-1), respectively. In conclusion, ioversol, iodixanol and ioxaglate inhibit platelet adhesion and P-selectin expression, as well as plasma coagulation. Platelets are more sensitive in relation to the inhibiting effect on plasma coagulation.

The effect of contrast media on the synovial membrane.

OBJECTIVE: To examine the effect of intra-articular injection of contrast media, sorbitol and normal saline on the synovial membrane. MATERIALS AND METHODS: Sixty three rabbits (126 knees) were used in this study. We injected the knees with amidotrizoate, ioxaglate, iopamidol, iotrol and diluted gadolinium-DTPA (2 mmol/l). Normal saline and sorbitol 27.25% were used for comparison. A histological and histochemical examination of the knees was carried out 1, 2, 10, 20, 30, 40 and 60 days after the injection. RESULTS: On histological examination, the knees injected with normal saline, ioxaglate and gadolinium-DTPA had a normal appearance. Intra-articular injection of amidotrizoate, iopamidol, iotrol and sorbitol caused early, mild and transient histological changes of the synovium (synovial hyperplasia, infiltration by leucocytes). Furthermore, the knees injected with amidotrizoate presented with late, extensive histological changes (severe synovial hyperplasia, moderate vascular dilatation, severe infiltration by leukocytes). CONCLUSION: The results suggest that the chemical structure and not the osmolality of the contrast media is the main cause for the histological changes of the synovium.

Contrast medium attenuates platelet activation and platelet-leukocyte cross-talk.

The influence of ionic and non-ionic contrast media (CM) on platelet and leukocyte activation and platelet-leukocyte crosstalk was investigated in hirudinized whole blood. The blood was incubated with and without the ionic CM ioxaglate and the nonionic CM iodixanol at 37 degrees C for 5 min, without or with stirring. Platelet and leukocyte activation and platelet-leukocyte aggregation were measured using whole blood flow cytometry. When blood samples were pre-incubated in the presence of 2%, 5%, and 10% of CM without stirring, both ioxaglate and iodixanol had little effect on unstimulated samples, but dose-independently decreased 1 microM ADP-induced platelet P-selectin expression and fibrinogen binding, and thus platelet-leukocyte aggregate formation. Ioxaglate had little effect on leukocyte CD11b expression, whilst iodixanol slightly enhanced resting and N-formyl-methionyl-leucyl-phenylalanine (fMLP; 0.1 microM)-stimulated leukocyte CD11b expression. Blood samples were also incubated with stirring to investigate the impact of CM (5% of ioxaglate or iodixanol) on platelet-leukocyte cross-talk. Collagen induced marked platelet activation and platelet-leukocyte aggregation, and subsequently elevated leukocyte CD11b expression. The latter was attenuated by ioxaglate and iodixanol, and was accompanied by reduced platelet-leukocyte aggregation. In conclusion, the CM ioxaglate and iodixanol attenuate platelet activation and platelet-leukocyte cross-talk. Inhibitory effects of the contrast agents on this cross-talk are apparently exerted by reducing heterotypic conjugation, and may be beneficial in connection with PCI.

Influence of contrast media (iopromide, ioxaglate, gadolinium-DOTA) on blood viscosity, erythrocyte morphology and platelet function.

The influence of contrast media on blood viscosity, erythrocyte morphology and platelet function was studied. In vitro blood was incubated with iopromide (Ultravist), ioxaglate (Hexabrix) or gadolinium-DOTA (Dotarem). Plasma viscosity and whole blood viscosity were measured and the mean erythrocyte volume and morphology were assessed. Platelet aggregation was measured with a PFA-100 instrument. In an ex vivo study on patients receiving these contrast media the same measurements as described above were done. All contrast media increased blood viscosity at high shear rate in a dose dependent manner (e.g. with ioxaglate: from 4.9+/-0.2 mPa x s to 8.6+/-0.5 mPa x s at 160 mg I/ml), decreased low shear viscosity (for ioxaglate: from 44.9+/-2.5 to 27.7+/-4.8 mPa x s), increased plasma viscosity (ioxaglate: from 1.2+/-0.1 to 2.8+/-1.3 mPa x s), decreased the mean erythrocytic volume (ioxaglate: from 89.7+/-1.4 to 79.7+/-2.0 fl) and decreased platelet aggregation. Iopromide induced an echinocytic shape transformation of erythrocytes. Ex vivo a decreased hematocrit and a consecutively decreased whole blood viscosity were found with iopromide and ioxaglate. We conclude that contrast media influenced blood rheology, erythrocytes and platelet aggregation in vitro and ex vivo.

The effects of carbon dioxide versus ioxaglate in the rat kidney.

PURPOSE: The renal medulla seems to be particularly vulnerable to vascular injection of iodinated contrast media, particularly in patients with preexisting renal dysfunction. The gas carbon dioxide is frequently used as an alternative to iodinated contrast medium in these patients. In this study, the renal effects of CO(2) are investigated and compared with those of the iodinated contrast medium ioxaglate. MATERIALS AND METHODS: Cortical and outer medullary blood flow (measured by laser Doppler flowmetry) and oxygen tension (Po(2); measured by oxygen microelectrodes) were recorded in anesthetized Sprague-Dawley rats given an intraarterial injection of ioxaglate (320 mgI/kg body weight), a volume-matched dose of CO(2), or Ringer solution. RESULTS: Injection of CO(2) induced a pronounced and transient decrease in cortical blood flow and Po(2) (approximately -45%), whereas outer medullary blood flow and Po(2) were transiently increased (+21% and +29%, respectively). In contrast, injection of ioxaglate did not influence cortical blood flow and caused outer medullary blood flow to decrease by 17%. Ioxaglate injection also resulted in a decrease in cortical and outer medullary Po(2) (-15% and -33%, respectively). Ringer solution affected none of the recorded parameters. CONCLUSIONS: Although injection of CO(2) markedly affected regional renal blood flow and Po(2), there were qualitatively different effects in the cortex and outer medulla compared with those seen after injection of ioxaglate. The pronounced decrease in medullary blood flow and Po(2) observed after injection of ioxaglate was absent in the animals injected with CO(2). This might suggest beneficial effects of the use of CO(2) instead of iodinated contrast media in patients with increased risk of developing renal failure.

Evaluation of the nitric oxide production in rat renal artery smooth muscle cells culture exposed to radiocontrast agents.

BACKGROUND: Radiocontrast agents (RC), substances largely used in diagnostic procedures, present the nephrotoxicity as one of its major side effects, which could be due to an altered synthesis of vasodilators. The aim of the present study was to evaluate the nitric oxide (NO) production in rat renal artery smooth muscle cells primary culture (rVSMC) exposed to RC. METHODS: The cells were treated for 72 hours with mannitol at 10% (MT10; 600 mOsm/kg H2O) or 35% (MT35; 2100 mOsm/kg H2O), with the nonionic iobitridol (IBT), the low-osmolality ioxaglate (IXG), the high-osmolality ioxitalamate (IXT), the nonionic, iso-osmolar iodixanol (IDX), and with lipopolysaccharide (LPS). We determined the NO and osmolality in the cell culture media and the cellular viability. RESULTS: By the Griess and chemiluminescence methods, the NO was not different in MT10 and IDX, but decreased in MT35, IBT, IXG, and IXT when compared with the control; it was increased in LPS and also decreased in all RC+LPS when compared with LPS. MT35, IXT, and IXT+LPS decreased the cellular viability, and the media osmolality was increased in MT35 and IXT compared with the control. CONCLUSION: The RC (except IDX) significantly reduced NO in rVSMC, which was more pronounced after IXT treatment (57.3%). This was not related to the reduced cell viability (15.8%) or to its high osmolality, because in MT35, with similar osmolality as IXT, NO decreased only 11.0% relatively to the control. Neither the media osmolality nor the cell viability was altered by IXG or IBT. The decreased NO could explain the vasoconstriction and, therefore, the acute renal failure by RC.

No difference among modern contrast media's effect on neointimal proliferation and restenosis after coronary stenting in pigs.

RATIONALE AND OBJECTIVES: Recent clinical trials indicate that the choice of radiographic contrast media (CM) may influence the late outcome of coronary interventions. This might be explained by the different effects of various CM on neointimal proliferation. METHODS: The effect of a 1-hour incubation of bovine aortic smooth muscle cells in ioxaglate or iopromide solution on in vitro cell division was tested. Furthermore, in 12 pigs randomized into 3 groups (iopromide, ioxaglate, and iosimenol; a novel nonionic dimer), coronary angiography was performed followed by implantation of stents. After 28 days, restenosis was assessed by quantitative angiography and histomorphometry. RESULTS: Compared with saline, CM did no change cell counts up to 15 days after incubation. Baseline parameters in the pigs indicated no difference between the test groups. After 28 days, the test groups showed no significant differences in the parameters characterizing in-stent restenosis. CONCLUSIONS: Under the experimental conditions iopromide, ioxaglate, and iosimenol had no or very similar direct or otherwise mediated effect on cell proliferation and restenosis.

Inflammatory markers increase following exposure to radiographic contrast media.

PURPOSE: Increased levels of markers of systemic inflammation have been noted in patients following coronary angiographic procedures. The purpose of the present study was to examine the influence of the type of the angiographic procedure as well as the type of radiographic contrast media (RCM) on markers of inflammation. MATERIAL AND METHODS: Thirty-seven patients undergoing diagnostic or interventional coronary angiographic procedures were randomly assigned to receive one of three RCM - an ionic low osmolar agent; a non-ionic, iso-osmotic agent; or a non-ionic, low osmolar agent. Sera were analyzed at baseline (prior to receiving RCM), and at 2, 6 and 24 h thereafter for interleukin (IL)-6 and soluble receptors for tumor necrosis factor alpha (TNFalpha)-1 and TNFalpha- 2. RESULTS: Statistically significant increases over time in each RCM group were noted for IL-6 and both TNFalpha receptors. Comparable increases in inflammatory markers were observed in patients undergoing diagnostic angiography and in patients undergoing an associated coronary intervention. While these markers increased following exposure to both ionic and non-ionic RCM, there was a consistent trend towards lessened marker release with non-ionic RCM. CONCLUSION: Both diagnostic and interventional coronary angiographic procedures are associated with an increase in serum inflammatory markers. While both ionic and non-ionic RCM are associated with increases in serum inflammatory markers, this increase may be attenuated with non-ionic RCM.

Involvement of proteinase-activated receptor-2 in mast cell tryptase-induced barrier dysfunction in bovine aortic endothelial cells.

We report here a direct modulation by mast cell tryptase of endothelial barrier function through activation of proteinase-activated receptor-2 (PAR-2). In cultured bovine aortic endothelial cells (BAECs), tryptase, trypsin and PAR-2 activating peptide impaired the barrier function as determined by the permeability of protein-conjugated Evans blue. The tryptase-induced barrier dysfunction was completely blocked by U73122, and partially reversed by xestospongin C, calphostin C or Y27632. The intracellular Ca(2+) was elevated by tryptase. It was notable that ioxaglate, a contrast material that degranulates mast cells, markedly increased the permeability when applied to BAECs in combination with mast cells, an action that was blocked by nafamostat, a potent tryptase inhibitor. Immunofluorescence analysis showed that actin stress fibre formation and disruption of VE-cadherin were observed after exposure to tryptase or ioxaglate in combination with mast cells. Therefore, it is suggested that mast cell tryptase impairs endothelial barrier function through activation of endothelial PAR-2 in a manner dependent on the phospholipase C activity.

In vivo comparative antithrombotic effects of ioxaglate and iohexol and interaction with the platelet antiaggregant clopidogrel.

RATIONALE AND OBJECTIVES: Experiments were designed to (1) compare the effects of iodinated contrast media (CM) on a rat model of arterial thrombosis, (2) evaluate which element of the ioxaglate solution supports its antithrombotic activity, and (3) investigate the interaction of ionic and non-ionic CM with the antiplatelet agent clopidogrel. MATERIALS AND METHODS: Carotid thrombosis was induced in rats by extravascular application of a filter paper soaked in FeCl3 (35% vol/wt), proximal to an ultrasonic flow probe. (1) The antithrombotic potential of low-osmolar ionic (ioxaglate Na/meglumine) or nonionic contrast media (iohexol and iodixanol) (all 1600 mg iodine/kg, IV) was assessed by measuring the time to occlusion (TTO) of the carotid artery and the thrombus weight (TW). (2) Isotonic saline and iso-osmolar (280 mOsm/kg) and hyperosmolar (560 mOsm/kg) solutions of meglumine hydrochloride, meglumine ioxaglate (560 mOsm/kg), sodium ioxaglate (600 mOsm/kg) and sodium and meglumine ioxaglate (commercial solution) were tested under similar conditions. (3) Interaction with clopidogrel was tested by injecting lower dose of CM (960 mg iodine/kg) 2 hours after clopidogrel (2 mg/kg per os). RESULTS: (1) Ioxaglate prolonged TTO when compared with saline (30.0 +/- 1.1 minute vs. 19.6 +/- 2.4 minutes, P< 0.001), whereas iohexol had no effect (21.3 +/- 1.3 minutes). Ioxaglate's effect was associated with a reduction in TW with ioxaglate versus saline (2.6 +/- 0.4 mg and 4.7 +/- 0.7 mg, respectively, P< 0.05) whereas TW remained unchanged in the iohexol group (4.2 +/- 0.4 mg). The nonionic dimer iodixanol induced a direct vasoconstrictor effect on the carotid artery and was consequently excluded from the study. (2) Neither iso-osmolar nor hyperosmolar solutions of meglumine had any effect on TTO whereas both sodium and meglumine salts of ioxaglic acid prolonged TTO, suggesting that the antithrombotic effect of ioxaglate is mediated by the ioxaglic acid moiety alone as neither meglumine, osmolality or sodium played a significant role. (3) A synergistic effect on TTO was found when ioxaglate was associated with clopidogrel whereas no such effect was observed with iohexol. CONCLUSIONS: These data show a greater in vivo antithrombotic potential for the ionic contrast medium ioxaglate than for the non-ionic contrast medium iohexol and, for the first time, a synergistic effect between a contrast medium and a platelet antiaggregant drug in vivo.

Effects of gentamicin, lipopolysaccharide, and contrast media on immortalized proximal tubular cells.

Aminoglycosides are widely used in the treatment of gram-negative bacterial infections. Gentamicin (GE) acts mainly in proximal tubular cells, where it is uptake via organic anion transport system and it induces a high incidence of nephrotoxicity, which is characterized by tubular necrosis [5] leading to acute renal failure in 10 to 50% of patients. Gram-negative bacteria has lipopolysaccharide (LPS) which is an endotoxin that cause renal damage. [1] Moreover, many patients are undergone exams using radiologic contrast, which is a risk factor to induce a hemodynamic change in the kidney and to develop acute renal failure. [6] Intracellular calcium [Ca2+]i is involved in renal cellular injury [7,3] and maybe mediate the effects provoked by these drugs. This study was performed to evaluate necrosis, apoptosis, and intracellular calcium levels ([Ca2+]i) in LLC-PK1 (epithelial cell line from pig kidney) induced by GE associated with LPS and a low-osmolality media, Hexabrix (HE).

Effect of an ionic compared to a non-ionic X-ray contrast agent on platelets and coagulation during diagnostic cardiac catheterisation.

The aim of the present study was to evaluate the effects of ionic (ioxaglate) and non-ionic (iopromide) contrast media on haemostatic parameters ex vivo. In 40 patients undergoing coronary angiography, platelet function (platelet reactivity and serotonin concentration) and coagulation markers [thrombin-antithrombin III complexes, prothrombin fragments (F1+2) and the D-dimers] were measured. The use of an ionic X-ray contrast agent (XCA) (ioxaglate) in diagnostic cardiac catheterisation angiography is associated with lower thrombin generation and lower activation of the platelet system than when a non-ionic XCA is employed (iopromide). The results thus confirm the results of various in vitro studies and animal investigations.