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Background Context: Ioxitalamate (Telebrix 300) is an ionic iodinated contrast medium commonly used for discography or percutaneous endoscopic lumbar discectomy (PELD), though it has side effects such as anaphylactic shock and renal toxicity. Indigocarmine is an organic compound dye with a distinctive blue color that is commonly used during PELD to stain the acidic, degenerated nucleus pulposus (NP). Although ioxitalamate and indigocarmine are widely used in spinal surgery, there have been no reports on their effects on NP cells. We studied the toxicities of both ioxitalamate and indigocarmine to NP cells., Purpose: To determine the toxicities of both ioxitalamate and indigocarmine to NP cells in vitro., Study Design: In vitro, controlled study of the toxicities of both ioxitalamate and indigocarmine to human NP cells., Methods: Nucleus pulposus cells were obtained via discectomy from lumbar disc patients and isolated. Nucleus pulposus cells were cultured in three-dimensional (3D) alginate beads with 0.001, 0.1, 10, and 100 mg/mL ioxitalamate, 0.00001, 0.001, 0.1, and 10 mg/mL indigocarmine, or a mixture of both for 1, 2, or 3 days. The living cells were analyzed with trypan blue staining. Fluorescence Activated Cell Sorting analysis using Annexin V and propidium iodide and 3D alginate bead immunostaining was performed to identify live, apoptotic, and necrotic cells., Results: Ioxitalamate, indigocarmine, and their combination induced statistically significant NP cell injury that was both time- and dose dependent (p<.05). Also, at the same concentration, ioxitalamate was more cytotoxic than was indigocarmine or the combination (p<.05). All three treatments also showed dose-dependent cytotoxicity according to flow cytometry and immunostaining., Conclusions: Ioxitalamate and indigocarmine are toxic to human NP cells in vitro in a time- and dose-dependent manner. We assume that ioxitalamate and indigocarmine may have similar effects in patients undergoing discography and PELD. Thus, we suggest that ioxitalamate and indigocarmine should be used carefully at low concentrations., (Copyright © 2013 Elsevier Inc. All rights reserved.)

To investigate the unrecognized role of renal efferent nerve activity (RENA) in iodinated contrast media (CM)-induced acute kidney injury, we explored the effects of CM on RENA, renal hemodynamics, plasma renin activity (PRA), reactive oxygen species (ROS) production, and renal injury in rats. Four types of CM including ioxitalamate (high osmolar and ionic), ioxaglate (low osmolar and ionic), iohexol (low osmolar and nonionic), and iodixanol (iso-osmolar and nonionic) were given iv (1600 mg I/kg body weight) to urethane-anesthetized female Wistar rats. We measured RENA by electrophysiologic recording techniques, renal blood flow with Doppler ultrasound, PRA by radioimmunoassay, and ROS by an in vivo chemiluminescence method. We graded the severity of CM-induced vacuoles in cortical tubular cells stained by hematoxylin and eosin and apoptosis production in outer medulla by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Besides, the effects of pretreatment with iv beta-adrenoceptor antagonist propranolol (10 mg/kg body weight), antioxidant N-acetylcysteine (100 mg/kg body weight), and renal denervation on CM-induced pathophysiologic parameters were determined. Ioxitalamate significantly increased RENA and renal vascular resistance, PRA, renal ROS production within 1 h, and formation of vacuoles and TUNEL apoptosis in renal tubular cells 2 h later; other CM had less effect on these parameters. On the other hand, propranolol, N-acetylcysteine, or renal denervation partially attenuated the ioxitalamate-aggravated responses on RENA, PRA, ROS production, and vacuole and TUNEL apoptosis formation in renal tubular cells. In conclusion, we suggest that ioxitalamate may induce acute tubular injury via aggravation of RENA, adrenergic signaling, PRA, and ROS production.

Objectives: The loss of renal function continues to be a frequent complication of the iodinated contrast agents used to perform diagnostic angiography and endovascular procedures. This study examined the hypothesis that contrast-induced renal injury is partly due to a decrease in cortical and medullary microvascular blood flow after the downregulation of endogenous renal cortical and medullary nitric oxide (NO) synthesis., Methods: Anesthetized male Sprague-Dawley rats (300 g) had microdialysis probes or laser Doppler fibers inserted into the renal cortex to a depth of 2 mm and into the renal medulla to a depth of 4 mm. Laser Doppler blood flow was continuously monitored, and the microdialysis probes were connected to a syringe pump and perfused in vivo at 3 muL/min with lactated Ringer's solution. Dialysate fluid was collected at time zero (basal) and 60 minutes after infusion of either saline or Conray 400 (6 mL/kg). Both groups were treated with saline carrier, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 30 mg/kg), L-arginine (400 mg/kg), or superoxide dismutase (10,000 U/kg), an oxygen-derived free radical scavenger. Dialysate was analyzed for total NO and eicosanoid synthesis. The renal cortex and medulla were analyzed for inducible NO synthase (iNOS), cyclooxygenase-2 (COX2), prostacyclin synthase, and prostaglandin E(2) (PGE(2)) synthase content by Western blot analysis., Results: Conray caused a marked decrease in cortical and medullary blood flow with a concomitant decrease in endogenous cortical NO, PGE(2), and medullary NO synthesis. The addition of L-NAME to the Conray further decreased cortical and medullary blood flow and NO synthesis, which were restored toward control by L-arginine. Neither L-NAME nor L-arginine (added to the Conray) altered cortical or medullary eicosanoids release. Medullary PGE(2) synthesis decreased when superoxide dismutase was added to the Conray treatment, suggesting that oxygen-derived free radicals had a protective role in maintaining endogenous medullary PGE(2) synthesis after Conray treatment. Conray did not significantly alter iNOS, COX-2, prostacyclin synthase, or PGE(2) synthase content., Conclusions: These findings suggest that the downregulation of renal cortical and medullary NO synthesis contributes to the contrast-induced loss of renal cortical and medullary microvascular blood flow. Preservation of normal levels of renal cortical and medullary NO synthesis may help prevent or lessen contrast-induced renal vasoconstriction and lessen contrast-induced renal injury found after diagnostic and therapeutic endovascular procedures.

Purpose: To quantitatively evaluate endothelial injury in vivo and to assess the time course of cellular repair after endothelial cell exposure to ionic and non-ionic contrast media., Material and Methods: Local changes at the cellular level following intraaortic injection of 1 ml of the ionic contrast agent ioxithalamate or 1 ml of the non-ionic contrast agent iomeprol, each with an iodine content of 300 mg/ml, were investigated using rat endothelium as an in vivo model. A sorbitol solution iso-osmolar to iomeprol served as control. Quantitative analysis of endothelial changes by autoradiography of 3H-thymidine-labeled endothelial cells was assessed after 3, 5 and 10 days, determining the 3H-thymidine index and the DNA synthesis rate., Results: Ioxithalamate showed a clear harmful effect on the endothelium, with an elevated 3H-thymidine index of 7.68% on day 3 and 6.89% on day 5, versus 2.97% on day 3 and 2.55% on day 5 for iomeprol and 2.29% on day 3 and 1.91% on day 5 for the control., Conclusion: Ionic contrast agents lead to reversible transient focal endothelial cell injury. No such side effect was detectable for non-ionic contrast agents.

The pathogenesis of radiocontrast nephropathy is poorly understood. In an animal model, inhibition of the synthesis of nitric oxide and prostaglandins appears to predispose rats to severe renal injury following the administration of radiocontrast. Here we have investigated whether administration of radiocontrast, as well as changes in renal medullary oxygenation following pharmacologic inhibition of nitric oxide and prostaglandin synthesis, might be evaluated by blood oxygenation level-dependent (BOLD) MRI. Nineteen anesthetized (Inactin 100 mg/kg) rats were studied. BOLD MRI measurements were performed following administration of L-NAME (N-nitro-L-arginine methyl ester, 10 mg/kg), Indomethacin (10 mg/kg), and a radiocontrast agent (sodium iothalamate 60%, 6 mL/kg). Marked sequential changes in medullary R(*)(2), presumably reflecting decline in medullary pO(2), were noted after each of the pharmacological interventions employed. These results, obtained by noninvasive MRI, are consistent with prior direct recordings of pO(2) and doppler flow in the rat renal medulla after administration of L-NAME, Indomethacin and iothalamate. Medullary oxygenation in rats was reduced by inhibition of the synthesis of prostaglandins and nitric oxide, as well as by intravenous injection of radiocontrast agents. BOLD MRI can noninvasively evaluate changes in medullary oxygenation in rats that appear to predispose acute renal failure. J. Magn. Reson. Imaging 2001;13:744-747., (Copyright 2001 Wiley-Liss, Inc.)

The response of insulin-like growth factor (IGF) I in acute renal failure was evaluated in a model of radiocontrast nephropathy associated with selective necrosis of medullary thick ascending limbs. In brief, rats were administered radiocontrast medium or vehicle injections for controls after combined inhibition of prostanoids and nitric oxide. Twenty-four hours after the insult, tissue mRNAs for IGF-I, the IGF-I receptor, and IGF-binding proteins (IGFBP) 1 and 3 were assayed in cortex, medulla, and liver by solution hybridization-RNase protection assay, and IGFBPs were measured in serum and tissue by Western ligand blotting. Cortical IGF-1 increased, whereas medullary IGF-I mRNA decreased. Renal IGFBPs decreased, whereas IGFBP-1 mRNA increased. The IGF system in the liver was unchanged. We conclude that general changes in renal IGFBPs in this experimental model of acute renal failure might increase the level of cortical IGF-I in a way that could modulate medullary recovery.

Purpose: To study the effects of iothalamate sodium and two dosages of iopromide in acute cerebral ischemia on infarction volume, neurologic performance, and mortality in a rat model of middle cerebral artery occlusion., Materials and Methods: Sixty-four rats underwent endovascular occlusion of the middle cerebral artery. Four hours later, 16 animals received iothalamate sodium (588 mg iodine per kilogram); 16, iopromide as a single bolus (518 mg iodine per kilogram); and 16, iopromide as a double bolus (1,036 mg iodine per kilogram). Sixteen animals received equivolumetric saline (control group). Neurologic score and body weight were recorded every 8 hours. Twenty-four hours after occlusion, all animals were killed; brains were stained to assess the infarction size., Results: Single and double doses of iopromide did not affect infarction volume or neurologic performance. Iothalamate caused an increase in infarction volume and worsening of the neurologic score (p < .05). Mortality rate was 25% in the iothalamate group, 12% in the control group, and 6% in the iopromide groups., Conclusion: Bolus injection of the nonionic iopromide does not statistically significantly affect infarction volume or cerebral ischemia symptoms. Nonionic rather than ionic contrast agents should be preferred during acute cerebral ischemia.

In a double blind clinical study, 50 patients with healthy kidneys were tested for the discharge of renal marker proteins before and after receiving a high or low osmoloar contrast medium (Meglium-Ioglicinat, Imeprol) using i.v. urography. The renal excretion of the tubular indicator enzymes alanine aminopeptidase, beta-Glutamyltranspeptidase and alkaline phosphatase increased in all patients after administration of the contrast media. The enzymuria was significantly lower with the non-ionic contrast medium with the ionic one, thus demonstrating that the non-ionic contrast medium has a lower nephrotoxic potential than the conventional ionic contrast medium. Three independent investigators evaluated the radiograms with regard to the contrast quality using prearranged criteria in a 5 point system. The diversity of the evaluations clearly favoured the non-ionic contrast medium.

Human radiocontrast nephrotoxicity is predicted by the presence of multiple risk factors, often associated with compromised renal circulation. To produce a simple model of radiocontrast nephropathy, rats were pretreated with indomethacin and N omega-nitro-L-arginine methyl ester (L-NAME, to inhibit nitric oxide synthesis) before the administration of iothalamate. Acute renal failure consistently developed, with a decline in creatinine clearance from 1.05 +/- 0.10 to 0.27 +/- 0.05 ml/min (P < 0.001) associated with selective necrosis of 49 +/- 9% of medullary thick ascending limbs. Hemodynamic studies using laser-Doppler probes revealed that when injected alone, iothalamate increased outer medullary blood flow to 196 +/- 25% of baseline (P < 0.001). Pretreatment by L-NAME or indomethacin both reduced basal medullary blood flow and transformed the medullary vasodilator response to radiocontrast into vasoconstriction, with a prolonged reduction of medullary blood flow to less then half of baseline. Combined administration of indomethacin, L-NAME, and iothalamate lowered medullary blood flow to 12 +/- 4% of baseline. We conclude that prostanoids and nitric oxide have an important protective role in the renal response to radiocontrast material. Reduced synthesis of these vasoactive substances in renal/vascular diseases may predispose patients to radiocontrast nephropathy.

In lightly-anesthetized dogs, ionic or non-ionic RCM (Iotalamato and iohexol, respectively) when injected by intracarotid route (i.c.), elicit a pain response comparable to that caused by bradykinin (BK) or capsaicin (CAP). This response, which is characterized by vocalization, hyperpnea, bradycardia and neck muscle contraction, was dose dependent and related to the osmolarity of the RCM. In the present study we observed that indomethacin did not interfere with CAP and RCM-induced pain at dose (2 mg/kg i.c.) that reduced BK-elicited responses. In contrast, Ruthenium Red (RR), in dose (1 mg/kg i.c.) that reduced CAP and/or RCM-induced effects did not affect BK-induced phenomena. We also verified that L-NAME (50 mg/kg i.c.) reduced the BK-, but not the CAP- and/or RCM-induced pain responses which suggests that an L-arginine-derived NO or related compound is involved in BK activation of perivascular nociceptors. Indeed, we found that i.c. injection of 20 mg of S-nitrosocysteine, a putative EDRF, caused BK-like responses. On the other hand, RCM and CAP appear to activate the same RR sensitive ionic channels of primary afferent endings. Therefore, RR-analogues could constitute a novel approach to minimizing or eventually abolishing the RCM side effects.

Recent studies indicate that endothelin (ET), a potent endogenous systemic and renal vasoconstrictor peptide, may mediate decreases in GFR in models of acute renal dysfunction. Moreover, in an animal model of radiocontrast-induced nephropathy (RCIN), it was recently demonstrated that early renal hemodynamic responses to radiocontrast are attenuated by intra-arterial atrial natriuretic factor (ANF), which prevents subsequent RCIN. The studies presented here were therefore designed to determine whether i.v. infusion of radiocontrast produces increases in endogenous plasma and urinary ET and whether these responses are modulated by intra-arterial ANF in an animal model of RCIN. In these studies, dogs with pacing-induced heart failure received i.v. radiocontrast in the presence and absence of an intra-aortic infusion of ANF. Significant increases in both plasma and urinary ET were observed during and after radiocontrast. Although coadministration of ANF did not prevent increases in plasma and urinary ET, ANF preserved renal function acutely in this model of RCIN by increasing GFR above baseline levels.

We evaluated the acute changes in cortical and outer medullary oxygen tension and the alterations in renal function and morphology within the first 90 minutes after the administration of indomethacin and iothalamate to anesthetized Sprague-Dawley rats. Both agents were found to produce marked and protracted outer medullary hypoxia averaging 12 +/- 4 and 9 +/- 2 mm Hg, respectively (mean +/- SE). Given together to salt depleted uninephrectomized rats they produced an early hypoxic injury localized selectively in the outer medulla. This lesion progressed from 3 +/- 1% of medullary thick ascending limbs (mTALs) at 15 minutes to 22 +/- 7% at 24 hours. Condensed "dark" cells were observed at 15 minutes, probably representing a type of early injury. Residual red cell mass, quantified in the outer medullary vasculature of perfusion-fixed kidneys and presumably reflecting stasis, was substantially increased in iothalamate treated rats. Red cell mass in the interbundle zone correlated with mTAL necrosis. Taken together, these results show an early period of medullary hypoxia, accompanied by a selective injury to mTALs in the central interbundle zone with apparent stasis. These findings contrast sharply with the ischemia-reflow pattern of renal damage and emphasize the important role of medullary hypoxia in the genesis of acute renal failure in this model.

The authors compared the renal toxicity of the low osmolality radiocontrast agents, iohexol and ioxaglate, and the ionic agent, iothalamate, at equivalent iodine dose, using experimental models in vitro and in vivo. In isolated perfused rat kidneys, all agents induced comparable biphasic hemodynamic changes, associated with similar declines in glomerular filtration rate (GFR) and tubular necrosis. In two different in vivo models (using multiple insults combined with the administration of radiocontrast), iothalamate appeared to induce more severe morphologic injury. Despite similar nephrotoxic potential in vitro, the newer radiocontrast agents, iohexol and ioxaglate, cause in vivo less renal injury than iothalamate in the experimental models.

Radiocontrast-induced nephropathy (RCIN) is a clinically important cause of acute renal failure with no effective treatment. Recognizing the high incidence of RCIN in humans with severe congestive heart failure (CHF), this study was designed to test the hypotheses that dogs with experimental CHF are at increased risk for RCIN and that pharmacologic renal levels of atrial natriuretic factor (ANF) can prevent RCIN in this model. In chronic experiments, three groups of five conscious dogs received intravenous radiocontrast (7 ml/kg). One group consisted of normal controls, while the two other groups had experimental CHF induced by eight days of ventricular pacing at 250 beats per minute. One of the CHF groups received an infusion of ANF (30 ng/kg/min) into the suprarenal aorta for one hour before, during and after the infusion of radiocontrast to achieve pharmacologic renal plasma levels. Renal function remained stable in the normal controls in contrast to the consistent decreases in daily creatinine clearance during the five days following radiocontrast in experimental CHF. In addition, ANF prevented radiocontrast-induced reductions in creatinine clearance in dogs with experimental CHF. Additional studies performed in two groups of anesthetized dogs with experimental CHF demonstrated that, in this model of RCIN, the reduction in renal function appears biphasic, and the action of ANF may be to increase glomerular filtration rate prior to radiocontrast, thus allowing a maintenance of renal function during and after radiocontrast.

Sodium iothalamate was injected intravenously into mice to test the hypothesis that reactions to contrast media are controlled by the central nervous system. Particular emphasis was placed on (a) the effect of the limbic portion of the brain on the hypothalamus and (b) the outflow through the autonomic nervous system. Diazepam and hexamethonium significantly affected the LD50; in addition, in comparison trials with control mice, they markedly decreased the death rate (p < 0.0005). High doses of methylprednisolone sodium succinate, given every 6 hours before the contrast medium, had no effect.

Groups each consisting of ten patients underwent lumbar and cervical myelography with metrizamide and iopamidol, together with a control group of ten patients who underwent lumbar punctures only. These groups were studied with a psychopathometric test procedure in order to demonstrate and quantify mental disturbances. It was shown that in contrast to myelography with iopamidol, mild mental disturbances are common after myelography with metrizamide. The severity of the mental disturbances after myelography with metrizamide was dependent on the quantity of contrast medium which diffused into the intracranial space after myelography, suggesting a dose-related neurotoxic effect of this substance. Such a correlation was not found with iopamidol.

Intravenous injections of ionic contrast media increase extravascular lung water in patients with elevated left atrial pressure, particularly in the presence of myocardial ischemia. The authors compared bolus injections of sodium methylglucamine diatrizoate and iopamidol on extravascular lung water at several levels of left atrial pressure in dogs. Methylglucamine increased lung water by a maximum of approximately 25-30% above baseline levels at low (less than 3 mm Hg), moderate (approximately equal to 15 mm Hg), and elevated left atrial pressures (greater than or equal to 25 mm Hg). At matched pressures, the peak change in lung water in the dogs given iopamidol was +4%, +7%, and +6%, respectively. In dogs with myocardial ischemia, the differences were even more pronounced (+45%, +60%, and +70%, respectively, for ionic media, and +7%, +12%, and +21% for iopamidol). The authors caution against using ionic contrast media in patients with left ventricular dysfunction, particularly associated with ischemia. In such cases, non-ionic media appear safer.

Omnipaque (iohexol) 350 mg I/ml has been compared with Telebrix (ioxithalamate) 380 mg I/ml in 48 patients undergoing intravenous urography. The contrast medium dose corresponded to 400 mg I/kg body weight. No cardiovascular reactions (BP and pulse rate) were observed. Subjective reactions occurred somewhat more frequently after Telebrix than after Omnipaque. Sensation of warmth was significantly less with Omnipaque (p less than or equal to 0.05). The overall radiological quality was equally good for the two contrast media.

As part of a general safety study of iopamidol, a nonionic iodinated contrast agent, urine N-acetyl-beta-glucosaminidase enzyme assays were done to compare the renal toxicity of iopamidol with that of iothalamate and diatrizoate. In a randomized study of 30 patients for computed body tomography and another 30 patients for angiography, 10 in each group were injected with iopamidol, 10 with iothalamate, and 10 with diatrizoate. After computed tomography or angiography with the three agents, there was no significant difference in urinary enzyme levels among the groups. The nephrotoxicity of iopamidol appears equivalent to that of diatrizoate and iothalamate.

Iopamidol, a new, nonionic contrast agent, was evaluated in 18 patients undergoing excretory urography. None of the 18 patients experienced any side effects or adverse reactions. No abnormalities were noted in serum chemistries, complete blood cell counts, urinalyses, or electrocardiograms. The half-life of iopamidol in 17 patients with normal renal function was 2.5 hr. The urograms were judged to be of good or excellent quality in 15 of 16 patients using doses of 200 and 250 mg l/kg of iopamidol. Two patients who were studied using a dose of only 120 mg l/kg had urograms rated poor. Fifteen iopamidol urograms (mean iodine dose, 17.4 g) were compared in a blind fashion with 15 meglumine diatrizoate studies (iodine dose, 29 g). No qualitative difference could be detected between the two groups of urograms. Iopamidol may provide equal-quality diagnostic studies with a lower iodine dose and perhaps greater safety than the currently used ionic agents.

L-5-alpha-hydroxypropionylamino-2,4,6-triiodoisophthalic acid di-(1,3-dihydroxy-2-propylamide), abbreviated Iopamidol, a new non-ionic water soluble contrast agent for angiography, myelography, ventriculography and for contrast reinforced computer-assisted axial tomography is described. Extensive preclinical testing showed favorable physico-chemical features of the new compound, low systemic toxicity, excellent cardiovascular and renal tolerability, very mild effects on the blood-brain barrier and on nervous tissue.

Electron microscope evaluation of choroid plexus and ependyma following single cerebral intraventricular injections of Conray 60 and Pantopaque was carried out on 35 rats and 4 dogs. The animals were sacrificed at periods ranging from 1 hour to 4 months. Conray was not detected with the light or electron microscope; however, Pantopaque was presumptively localized as electron-dense masses associated with lipid-like bodies at the ventricular interface of both choroidal and ependymal epithelium. Conray 60 injections consistently induced convulsions in rats. Histological studies demonstrated moderate cellular damage and multilayered proliferation of ependymal epithelium. Morphological damage following Pantopaque was more severe and widespread in both choroid plexus and ependyma suggesting that, of the two agents, Conray may have the greater clinical potential provided that the associated convulsions are controlled by appropriate measures.

The causal relationship between a myelogram with an aqueous contrast medium and postmyelographic arachnoiditis has not been clarified. Primates after myelography with metrizamide or meglumine iocarmate were studied with fluorescent microscopy, energy dispersion analysis and with scanning and transmission electron and light microscopy. All controls and, up to the eighth day after myelography, all treated animals had normal-appearing arachnoid membranes by microscopy. After eight days the treated animals had progressively more severe arachnoid fibrosis. Energy dispersive analysis revealed iodine in the arachnoid only up to 24 hours after myelography. Fluorescent microscopy revealed no evidence of immune complexes in the arachnoid. The chronic effects of water-soluble media on the arachnoid are not apparently mediated by contrast medium persisting in the arachnoid or by immune complexes.

Lung tissue reaction to endobronchial application of iopamidol and ioxithalamate were compared by chest radiograph and histological examination in the rat. Radiographs cleared within hours in both groups. Tissue reaction after ioxithalamate application was significantly more pronounced than with iopamidol and included macrophage response, partial atelectasis, and intra-alveolar and interstitial oedema. Different from iopamidol, ioxithalamate induced a significantly stronger reaction than tracheotomy alone. Because no important significant side effects were observed on chest radiographs or in lung histology, iopamidol is recommended for the radiological examination of the gastrointestinal tract in patients with an increased risk of aspiration.

Isolated segments of the right jugular veins of six mongrel dogs were exposed to solutions of 60% diatrizoate (3 dogs) and 60% iopamidol (3 dogs) in vivo. Normal blood flow was re-established after 3 minutes of exposure to the contrast material. The left jugular veins served as controls. Veins were harvested at 1, 24, and 48 hours and studied by light and scanning electron microscopy. Changes consisting of cellular swelling, denudation, platelet aggregation and fibrin deposition were uniform and prominent with diatrizoate. Response to iopamidol was minimal consisting only of cellular swelling. The study suggests that post-phlebographic thrombophlebitis may be reduced by the use of nonionic contrast materials.