Effects of iodinated contrast media on endothelium: An in vitro study (original) (raw)
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Effects of iodinated contrast media on blood and endothelium
European radiology, 2006
The aim of the study was to assess the effects of iodinated contrast media on blood components and endothelium based on experimental and clinical studies and to produce clinically relevant guidelines for reducing thrombotic and hematologic complications following the intravascular use of contrast media. A report was drafted after review of the literature and discussions among the members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology. The final report was produced following discussion at the 12th European Symposium on Urogenital Radiology in Ljubljana, Slovenia (2005). Experimental data indicate that all iodinated contrast media produce an anticoagulant effect and that this effect is greater with ionic contrast media. Several of the in vitro and experimental in vivo studies on haematological effects of contrast media have not been confirmed by clinical studies. Low- or iso-osmolar contrast media should be used for diagnostic and interventional...
Effects of Ionic and Nonionic Contrast Media on Endothelium and on Arterial Thrombus Formation
Acta Radiologica, 1996
The aims of the present study were to investigate whether ionic and nonionic contrast media (CM) affect: 1) the procoagulant and fibrinolytic activities of cultured human vessel endothelium; and 2) early events of tissue-factor-induced arterial thrombus formation under conditions which may follow a percutaneous transluminal coronary angioplasty (PTCA) procedure. The following 3 CM were studied: iohexol (nonionic monomer, Omnipaque); iodixanol (nonionic dimer, Visipaque); and ioxaglate (ionic dimer, Hexabrix). Saline (0.9%) and glucose (40 vol%) were used as control. Exposing endothelium to 40 vol% CM for 10 min did not affect the selected parameters of cellular procoagulant (tissue factor), anticoagulant (thrombomodulin), fibrinolytic (tissue plasminogen activator) or antifibrinolytic (plasminogen activator inhibitor-1) activity or antigen. However, ioxaglate had a profound impact on the cell morphology, which was noted already after one minute of exposure. The cells contracted and rounded, exposing large areas of extracellular matrix. Iohexol showed this phenomenon to a considerably lesser extent, whereas iodixanol induced a slight swelling of the cells without detectable exposure of extracellular matrix. The effect of the respective CM on tissue-factor-driven thrombus formation at an arterial shear rate of 2600 s-1 was studied in an ex vivo parallel-plate perfusion chamber device. In this model, human native blood was passed over a tissue factor/phospholipid-rich surface following 30 s exposure to 100% CM. The CM was washed out by nonanticoagulated blood drawn directly from an antecubital vein by a pump positioned distal to the perfusion chamber. Such a pre-exposure of the procoagulant surface to iodixanol reduced the fibrin deposition around the platelet thrombi by 50% (p<0.01). However, iohexol and ioxaglate did not affect fibrin deposition. None of the 3 CM affected the recruitment of platelets in the thrombi, since similar values were obtained with pre-exposure to 40 vol% of saline. Iodixanol appears to be most biocompatible with endothelium, and has a moderate inhibitory effect on fibrin deposition in flowing blood. This differs from iohexol, and in particular from ioxaglate, which induce endothelial changes in morphology with no effect on fibrin deposition. Since none of the CM affected the platelet aggregate formation, and since ioxaglate has been reported to have stronger anticoagulant and antithrombotic properties than iodixanol or iohexol in in vitro assays, it is apparent that these properties were not reflected in thrombus formation under the experimental conditions of high arterial shear.
The British journal of radiology, 2000
The aim of the study was to determine the effects of radiographic contrast media (RCM) on proliferation and apoptosis of human vascular endothelial cells. Human umbilical vein endothelial cells (HUVECs) were exposed for either 1 min or 15 min to RCM (diatrizoate, ioxaglate, iopromide, iotrolan) at an iodine concentration of 250 mgl ml-1. Controls were complete growth medium (CGM) and saturated mannitol (osmotic control). [3H]thymidine incorporation was used to determine cell proliferation 24 h after exposure. Apoptosis was determined at 1 h and 6 h by terminal uridine nick end labelling (TUNEL), time lapse video microscopy (TLVM) and DNA electrophoresis. Mean proliferation rates (%) (+/- SEM) (p-values compared with the CGM control) at 1 min and 15 min, respectively, were: diatrizoate: 31.9 (10.6), 5.8 (1.5) (p < 0.001); ioxaglate: 48.4 (10.9), 20.4 (4.5) (p < 0.001); iopromide: 63.4 (8.7), 58.2 (10.2) (p < 0.05); iotrolan: 84.7 (7.3), 72.8 (12.4) (p = ns); saturated mannit...
Clinical hemorheology and microcirculation, 2012
After intra-arterial administration of several radiographic contrast media (RCM) a disorder of the downstream microcirculation with regard to blood flow velocity in microvessels and to tissue oxygen partial pressure in the myocardium of the pig heart was described. Iodixanol did not induce such a microcirculatory disorder in the myocardium of the beating heart of pigs. Whether the morphological changes reported in venous endothelial cells after incubation in culture media supplemented with RCM in vitro coincide with a serious endothelial cell dysfunction is not known. In this study we wanted to get information on possible states of dysfunction or perturbation of venous and arterial ECs through the release of prostacyclin, which was shown to follow the perturbation of ECs. Functionally confluent venous endothelial cells on extracellular matrix secreted great amounts of prostacyclin in reaction to the RCMs indicating a clear perturbation of the ECs. This was not the case in arterial E...
The haemodynamic effects of iodinated water soluble radiographic contrast media: a review
European Journal of Radiology, 1998
All classes of iodinated water-soluble radiographic contrast media (RCM) are vasoactive with the iso-osmolar dimers inducing the least changes in the vascular tone. The mechanisms responsible for RCM-induced changes in the vascular tone are not fully understood and could be multifactorial. A direct effect on the vascular smooth muscle cells causing alterations in the ion exchanges across the cell membrane is thought to be an important factor in RCM-induced vasodilatation. The release of the endogenous vasoactive mediators adenosine and endothelin may also play a crucial role in the haemodynamic effects of RCM particularly in the kidney. In addition, the effects of RCM on blood rheology can cause a reduction in the blood flow in the microcirculation. The purpose of this review is to discuss the pathophysiology of the haemodynamic effects of RCM and to offer some insight into the biology of the endothelium and vascular smooth muscle cells as well as the pharmacology of the important vasoactive mediators endothelin and adenosine.
British Journal of Pharmacology, 1996
We have used rings of rabbit thoracic aorta to investigate the vasorelaxant properties of two different classes of non-ionic iodinated radiographic contrast media (IRCM) and the mechanisms, underlying their mode of action. lohexol (a triiodinated monomer) was compared with iodixanol (a hexaiodinated dimer). 2 lohexol and iodixanol both relaxed phenylephrine (0.3 gM) constricted rabbit aorta in a concentration-dependent manner that did not depend on the presence of an intact endothelium. When expressed as a function of iodine concentration, iodixanol caused significantly less relaxation than iohexol. However, the extent of relaxation was similar for both IRCM when expressed on a molar basis. Furthermore, increasing the molarity of the buffer to comparable levels with mannitol evoked only a small (-15%) relaxation of phenylephrine-induced tone. 3 Ouabain (10 gM) significantly inhibited both iohexoland iodixanol-induced relaxations by-30%. 5-(N-Ethyl-N-isopropyl)-amiloride (EIPA, 100 nM) significantly inhibited iohexol-induced relaxation to the same extent as ouabain, but did not alter the vasorelaxant effect of iodixanol. Co-incubation with ouabain and EIPA had an additive effect in the case of iohexol, increasing inhibition of relaxation to-60%, whereas inhibition of iodixanol-induced relaxation by the combination of ouabain plus EIPA did not differ from that of ouabain alone. 4 Replacing NaCl with N-methyl-D-glucamine (NMDG) to lower extracellular [Na+] and thereby inhibit Na+-Ca2" exchange, attenuated the relaxation evoked by iohexol or by iodixanol (by-25%) in each case. 5 We conclude that iohexoland iodixanol-induced vasorelaxation in rabbit aorta is mediated through a direct action on vascular smooth muscle that is not simply a consequence of altered osmolality. It involves modulation of the Na+-K+ ATPase and, in the case of iohexol, Na+-H+ exchange. Both agents also appear to modulate Na+-Ca2+ exchange, through direct and/or indirect mechanisms. This is the first study to show specific pharmacological differences between monomeric and dimeric contrast media in vascular smooth muscle. Keywords: Contrast media; vasorelaxation; ion exchange; iohexol; iodixanol whereas in the present study pure compounds were dissolved directly into physiological buffer to eliminate secondary effects due to alterations in the net ionic composition of the incubation medium. Methods Isolated ring preparations Author for correspondence. Male, New Zealand White rabbits (2.0-2.5 kg) were killed by an overdose of sodium pentobarbitone (120 mg kg-',
The American Journal of Cardiology, 1989
A double-blind randomizedstudy was performed in 60 patients to compare the electrocardiographic and hemodynamic changes induced during cardiac angiography by 2 contrast media with relatively low osmolality. loxaglate meglumine sodium, an ionic dimer contrast medium, was compared with iopamidol, a nonionic compound. Of the 30 patients who received ioxaglate, 13 (43%) experienced a mild to moderate adverse reaction to the contrast media, while only 2 of the 30 patients (7%) in the iopamidol group had similar side effects (p <0.005). Significant prolongations of the QT intervals occurred with the ioxaglate injections. The QT intervals increased from 402-f 46 to 442 f 59 ms (p <O.OOl) with the right coronary artery injection and similar changes were observed after the left coronary artery injection and left ventriculography. Significant ST-segment and l-wave amplitude changes also occurred in the ioxaglate group. With iopamidol injections, there were no significant changes in any of these parameters. After the left ventriculogram, there were similar decreases in the systolic arterial pressures in both groups (-14 f 10 mm Hg with ioxaglate and-21 f 9 mm Hg with iopamidol). The left ventricular end-diastolic pressures increased after the ventriculogram in both groups (5 f 5 vs 2 f 3 mm Hg with ioxaglate and iopamidol, respectively, 60 seconds after the injection). This report demonstrates that mild to moderate adverse reactions, QT-interval prolongations, ST and T-wave changes were significantly greater during coronary angiography with ioxaglate when compared with iopamidol. Thus, despite similar osmolalities, the nonionic contrast medium (iopamidol) appears to be better tolerated than the ionic dimer (ioxaglate) during coronary angiogapb rdiol 1989
Ionic versus nonionic contrast media: safety, tolerance, and rationale for use
Urologic radiology, 1989
After several years of clinical experience worldwide and numerous high-quality, randomized controlled trials in humans, the marked improvement in patient tolerance and safety of low osmolar contrast media (ionic and nonionic) has been demonstrated. Iohexol (Omnipaque), Iopamidol (Isovue), Ioxaglate (Hexabrix), and Ioversol (Optiray) are all now available in the United States.