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Hemodynamic effects of high versus low-osmolar contrast media for ventriculography in severe aortic stenosis.

The hemodynamic effects of high- (diatrizoate meglumine/sodium) and low- (iopamidol) osmolar contrast administration for left ventriculography were compared in 15 patients with severe aortic valve stenosis. Patients were similar with respect to aortic valve gradient, aortic valve area, age, body surface area, and baseline hemodynamics as well as associated coronary disease and valvular insufficiency. Administration of diatrizoate meglumine/sodium was associated with a 22% increase in heart rate, and marked (27%) decrease in left ventricular systolic pressure, with a small (15%) increase in left ventricular end diastolic pressure. In contrast, administration of larger volumes of iopamidol was associated with only a slight (9%) increase in heart rate, a small (6%) decrease in left ventricular systolic pressure, and a smaller (6%) increase in left ventricular end diastolic pressure. In patients with severe aortic valve stenosis iopamidol may offer a safer hemodynamic profile than diatrizoate meglumine/sodium.

Aortic Valve Stenosis↗

Influence of radiographic contrast agents on quantitative coronary angiography.

PURPOSE: Quantitative angiographic studies on the vasomotility of epicardial coronary arteries are gaining increasing relevance. We investigated whether radiographic contrast agents might influence coronary vasomotor tone and thereby the results of such studies. METHODS: Coronary angiograms were taken in 12 patients with coronary artery disease at intervals of 5, 3, 2, and 1 min with the low-osmolar, nonionic contrast agent iopamidol 300, and were repeated at identical intervals with the high-osmolar, ionic agent diatrizoate 76%. RESULTS: Quantitative cine film analysis demonstrated no significant diameter changes in angiographically normal and stenotic coronary arteries with iopamidol. With diatrizoate, however, normal segments were dilated 2% +/- 2% (p < 0.01) after 2 min and 10% +/- 3% after the 1 min interval (p < 0.001). Stenoses showed no uniform responses to diatrizoate. CONCLUSION: Low-osmolar, nonionic contrast agents should be preferred for quantitative angiographic studies on epicardial coronary vasomotility. When using ionic contrast agents, injection intervals of at least 3 min are required.

Aged↗

Effects of ionic and nonionic contrast media on coronary diameter and blood flow in chronically instrumented dogs.

The effects of intracoronary administration of ionic and nonionic contrast media on coronary circulation were studied in 14 chronically instrumented dogs. A pair of 10 MHz piezoelectric crystals and an electromagnetic flow probe were placed on the left circumflex coronary artery, under sterile conditions, to measure the epicardial coronary diameter and coronary blood flow, respectively. A polyethylene tube for drug infusion was inserted into the circumflex coronary artery proximal to the sonomicrometers. In the conscious dogs (n = 8), iopamidol, 2 ml and 5 ml increased the coronary diameter by 64 +/- 19 microns and 66 +/- 19 microns and coronary blood flow by 35 +/- 10% and 61 +/- 18%, respectively (p less than 0.01 vs control level). Meglumine diatrizoate, 2 ml and 5 ml, increased coronary diameter by 102 +/- 20 microns and 114 +/- 18 microns and coronary blood flow by 87 +/- 32% and 107 +/- 26%, respectively (p less than 0.01 vs control level). In the anesthetized dogs (n = 6), a bolus intracoronary injection of 5 ml iopamidol and meglumine diatrizoate within few seconds increased the coronary diameter by 103 +/- 23 microns and 164 +/- 39 microns (p less than 0.05) and increased the coronary blood flow by 126 +/- 33% and 180 +/- 40% (p less than 0.05), respectively. Balloon denudation of the endothelium was performed in six anesthetized dogs. The increases in coronary diameter and coronary blood flow after a bolus injection of contrast medium remained the same after the denudation. Thus application of iopamidol seems to be more suitable than meglumine diatrizoate for quantitative coronary angiography because of the milder and more transient effects on coronary circulation.

Acetylcholine↗

The preparation and characterization of liposomes containing X-ray contrast agents.

Unilamellar phospholipid vesicles loaded with the water-soluble, ionic X-ray contrast agent diatrizoate (Hypaque, Renografin) were manufactured by reverse-phase evaporation for use as organ-enhancing agents in X-ray computed tomography. Encapsulation efficiency was determined as a function of various diatrizoate concentrations in vesicles of varying lipid composition. Loss of encapsulated diatrizoate over 24 h was examined in vesicles composed of several egg phosphatidylcholine/cholesterol ratios. Size estimates for loaded vesicles were obtained by negative-stain electron microscopy, Millipore filtration and light microscopy. Intravenous in vivo injection of loaded vesicles in the rat resulted in significant enhancement of both spleen and liver on subsequent scans. Vesicles were similarly prepared with the water-soluble, nonionic agent metrizamide (Amipaque). Encapsulation efficiency was determined, and in vivo behavior was observed.

Animals↗

Cytotoxicity of radiocontrast agents on polarized renal epithelial cell monolayers.

OBJECTIVE: Radiocontrast-induced nephropathy is a clinically important complication of coronary angiography. The cellular mechanisms of radiocontrast-induced renal dysfunction are not clear. Since tubular transport functions depend on the polarity of renal epithelial cells, we investigated the effects of radiocontrast agents on polarized tubular cells in vitro. METHODS: We studied the effects of iso-iodine concentrations (37 and 74 mg iodine/ml) of an ionic (diatrizoate) and a non-ionic (iopamidol) monomeric radiocontrast agent and of hyperosmolal mannitol control solutions on filter-grown renal epithelial cell (MDCK, LLCPK) monolayers in vitro. The cytotoxicity was assayed by measurement of cell viability, transepithelial resistance, inulin permeability and (polarized) cellular enzyme release. The polarized MDCK cell phenotype was assessed by transmission electron microscopy and indirect immunofluorescence microscopy using monoclonal antibodies against specific apical (gp135) and basal (gp60, uvomorulin) MDCK surface markers. RESULTS: The radiocontrast agents reduced cell viability to a greater extent than hyperosmolal mannitol solutions in both cell lines; diatrizoate was more toxic than iopamidol. LLCPK cells were more susceptible to radiocontrast cytotoxicity than MDCK cells. This cytotoxicity was associated with an alteration of MDCK cell polarity as assessed by the redistribution of surface marker proteins. CONCLUSIONS: Diatrizoate is more toxic than iopamidol, which is partly related to its higher osmolality. The cytotoxicity of radiocontrast agents induces a redistribution of polarized membrane proteins which could contribute to the pathophysiology of radiocontrast-induced nephropathy.

Animals↗

Post-ERCP pancreatitis: randomized, prospective study comparing a low- and high-osmolality contrast agent.

Diagnostic and therapeutic ERCPs are complicated by pancreatitis in 1% to 10% of patients, and evidence suggests that the contrast agent used for ERCP may be important in the pathogenesis of such pancreatitis. This prospective, double-blind study was undertaken to determine whether the use of a low-osmolality, nonionic contrast agent (Omnipaque 300; iohexol, 672 mOsm/kg H2O) would reduce the frequency and severity of postprocedure pancreatitis as compared to a high-osmolality, ionic contrast agent (Hypaque 50%; diatrizoate sodium, 1515 mOsm/kg H20). Six hundred ninety patients undergoing diagnostic ERCP (pancreatogram, cholangiogram, or both) either with or without sphincter of Oddi manometry and therapy were randomized to iohexol or diatrizoate sodium. Postprocedure pancreatitis was diagnosed when the serum amylase or lipase level was elevated to at least four times the upper limits of normal at 18 hours and was associated with increased abdominal pain persisting for at least 24 hours after the procedure that required administration of narcotic analgesics. The pancreatitis was graded as mild, moderate, or severe depending on the length of hospital stay and the need for intervention. The overall frequency (7.2% versus 7.5%) and severity (4.3% mild, 2% moderate, 0.9% severe for the diatrizoate sodium group versus 4.3% mild, 2.6% moderate, and 0.6% severe for the iohexol group) of postprocedure pancreatitis and the frequency and severity within each procedure category were similar for the two contrast agent groups (p > .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cholangiopancreatography, Endoscopic Retrograde↗

Thrombogenic potential of contrast media in an experimental model of laser-induced thrombosis.

Controversy still exists about the pro- or antithrombotic side effects of contrast media used in daily medical practice. Recent reports have shown that various contrast media, including ionic compounds, have deleterious prothrombotic actions. A new evaluation of these adverse side effects is reported here, with the study of the dose-effect relationship. Two ionic (ioxaglate and diatrizoate) and two non-ionic contrast media (iopamidol and iohexol) were studied. Experiments were done on 22 groups of 5 Wistar male rats each, using a Laser Argon-induced thrombosis model in mesenteric microvessels. Three parameters were studied: the number of laser beams needed to induce platelet thrombus formation, the number of emboli, and the duration of embolization. Platelet count and platelet aggregation also were determined. Iopamidol and iohexol induced a significant rise in both the number of emboli and the duration of embolization in mesenteric microvessels at doses up to 1 mL/kg. Ioxaglate and diatrizoate also significantly increased these parameters at doses up to 2 mL/kg. All the products tested decreased platelet count, inducing a -17 to -30% variation from control values. Diatrizoate and ioxaglate inhibited platelet aggregation, while iopamidol and Iohexol behaved as activators. All non-ionic, and to a lesser extent, all ionic contrast media demonstrated prothrombotic properties.

Animals↗

Histamine release and contrast media-induced renal vasoconstriction.

RATIONALE AND OBJECTIVES: The authors' purpose was to investigate the role of histamine release causing renal vasoconstriction induced by application of contrast media, an important element in contrast medium-induced nephrotoxicity. MATERIALS AND METHODS: Isometric contractions in rabbit segmental renal arteries stimulated with KCl and increasing concentrations of the ionic contrast medium diatrizoate and the nonionic agents iomeprol and iodixanol were studied both with and without increasing concentrations of the histamine H1 and H2 blockers diphenhydramine and cimetidine. Histamine concentrations after contrast medium application were determined. RESULTS: Contrast-induced, dose-dependent, reversible renal artery contractions of 27%, 4.5%, and 5% of the control KCl contraction were found for diatrizoate, iodixanol, and iomeprol respectively. Those induced by the ionic contrast medium were statistically significantly higher (P < .01). Contractions were partially inhibited by diphenhydramine (49%) but not by cimetidine. Significant elevation of histamine concentrations (P < .05) was detected only after stimulation with diatrizoate but not with nonionic agents. CONCLUSION: Ionic contrast medium induces histamine release leading to renal vasoconstriction, which can be partly blocked by H1 blockers. Histamine has no effect on renal vasospasm induced by nonionic contrast media.

Animals↗

Systemic platelet effects of contrast media: implications for cardiologic research and clinical practice.

BACKGROUND: Angiographic contrast media cause platelet activation and decrease aggregability in vitro. We have previously shown in vitro a significant antiplatelet effect of contrast media at the concentrations obtained locally in the coronary artery during angioplasty. It is not known, however, whether a systemic effect is present. METHOD: Thirty patients undergoing diagnostic coronary angiography were prospectively randomized to receive the nonionic medium iohexol, ionic low-molecular-weight medium ioxaglate, or ionic high-molecular-weight medium diatrizoate. Platelet aggregability was measured before and after the investigation with whole blood electrical impedance aggregometry (WBEA) with collagen agonist and the PFA-100 (Dade, Miami, Fla) platelet function analyzer with combined shear, collagen, and adenosine diphosphate as agonists. RESULTS: With WBEA, with iohexol no difference in impedance change was seen: (medians and ranges) before, 9.8 Omega (4.8-19.2 Omega) versus after, 9.6 Omega (2-19.2 Omega) (P not significant [NS]). With ioxaglate a significant fall was seen: before, 8.6 Omega (6.4-15.2 Omega) versus after, 6.6 Omega (0-12.4 Omega) (P =.004). With diatrizoate a significant and greater fall was seen: before, 10.8 Omega (6.4-17.6 Omega) versus after, 6.6 Omega (0-10.8 Omega) (P =.002). With PFA, no difference in closure time was seen with any medium: iohexol before, 99 seconds (79-142 seconds) versus after, 142 seconds (63-128 seconds) (P NS); ioxaglate before, 120 seconds (75-258 seconds) versus after, 95 seconds (74-258 seconds) (P NS); and diatrizoate before, 114.5 seconds (65-250 seconds) versus after, 100.5 seconds (72-300 seconds) (P NS). CONCLUSIONS: Ionic but not nonionic contrast media have a systemic antiplatelet effect at diagnostic angiographic doses when measured with WBEA. Such an effect has not been shown before. This may explain the observed improved clinical outcome with ionic contrast media but also might confound platelet studies in coronary angioplasty.

Adult↗

Toxicity of X-ray contrast media in cell cultures.

Monolayer cell culture techniques for neuronal and glial cells and fibroblasts were used for the investigation of the direct toxicity of x-ray contrast media. The effect of various concentrations of sodium diatrizoate, methylglucamine salts of diatrizoate, iothalamate, iodamide, metrizamide, iocarmate, ioserate, and ioglycamate were studied. The intravenous biliary contrast medium--ioglycamate--was most toxic to all cell types. All the contrast media studied were somewhat toxic to neurons in the concentration of 50 mmol/l and showed variable glial toxicity. In equiosmolar concentrations the contrast media studied showed toxicity on neurons in the following order: iothalamate, diatrizoate, iodamide, ioserate, iocarmate, ioglycamate. Fresh metrizamide solution in equimolar concentrations showed the least toxic effects on neurons but interfered considerably with the growth and survival of glial cells. Metrizamide solution proved to be highly toxic to neurons when refrigerated for two weeks. Methylgucamine iocarmate produced a peculiar swelling of fibroblasts.

Cell Survival↗

Comparison of hot contrast material and hot saline for renal ablation in a canine model.

Renal ablation was performed in eight dogs with either 76% diatrizoate for normal saline. Both fluids were heated to 100 degrees C before injection. Coagulation necrosis and tubular atrophy were seen with both agents, indicating that much of the effectiveness of hot contrast material is due to heat. Diatrizoate also caused glomerular sclerosis, probably due to its inherent nephrotoxicity. Hot diatrizoate is probably more effective for renal ablation, but may not have an advantage over hot normal saline outside the kidney. Because of the risk of infection, prophylactic antibiotics are advised when renal ablation is performed with hot fluids.

Animals↗

Physiologic effects of contrast media in the rabbit.

The intravenous administration of contrast media (CM) is often associated with alterations in blood pressure (BP) and heart rate (HR). Osmolality is thought to play a role, but the magnitude and even the direction of change may vary under similar osmotic conditions indicating the involvement of other mechanisms. Conscious rabbits received sodium-meglumine diatrizoate (76%, 1 mL/kg, ear vein) every 10 minutes for 1 hour. A similar injection protocol was performed with normal saline and mannitol (36%), equiosmotic to the contrast agent. BP and HR were monitored continuously. Blood samples were collected at the midpoint between each injection for determination of hematocrit, serum osmolality, and iodine concentration. Group parameters at each time point were compared with the Student's t-test. The administration of mannitol caused changes in serum osmolality, hematocrit, and HR as great or greater than the changes caused by equiosmotic diatrizoate. However, BP increased significantly in the diatrizoate group but not in the mannitol group, relative to normal saline. These results suggest that osmolality is important for certain physiologic changes induced by CM, but that BP changes involve mechanisms in addition to osmolality.

Animals↗

Cytogenetic interactions of contrast media and antineoplastic drugs.

The cytogenetic interactions of ionic (diatrizoate, ioxaglate) and nonionic (iohexol) contrast media (CM) with antineoplastic drugs cyclophosphamide (CPA) and carmustine (CARM) were evaluated in a rat bone marrow cell model. Male Wistar rats were anesthetized with a 6% chloral hydrate solution and divided into five groups of five rats each. In protocol 1, three groups of rats received diatrizoate, ioxaglate, and iohexol (2.5 mL/kg) intravenously within 30 seconds. The remaining two groups were similarly injected with CPA and CARM (10 mg/kg). Control animals were injected with nonpyrogenic sterile water or saline solution. After 12 and 24 hours, the animals were killed with an overdose of chloral hydrate, and bone marrow smears were prepared for determining chromosomal damage in polychromatic erythrocytes (PCEs) by a micronucleus test. In protocol 2, CPA and CARM were injected, and 15 minutes later, bolus injections of diatrizoate, ioxaglate and iohexol were given through the same route. Both ionic and nonionic CM induced significant numbers of micronuclei in PCEs (P less than .05). CPA caused a severe cytogenetic effect, whereas CARM did not produce a significant number of micronuclei in PCEs compared with control. In protocol 2 experiments, antagonism with CPA and synergism with CARM was demonstrable. Clinical implication of the cytogenetic interactions between CM and antineoplastic drugs remains to be established.

Animals↗

Intravascular contrast media and the blood-brain barrier. Testing the new nonionic agent ioxilan.

The effects of diatrizoate, iohexol, and ioxilan on the blood-brain barrier (BBB) were investigated in normal and hypertensive rats. Anesthetized Wistar rats received 14C-inulin as an indicator for BBB disruption. Diatrizoate, iohexol, or ioxilan (350 and 175 mgI/mL) or normal saline was then injected into the carotid artery (2 mL in 30 seconds). Twenty minutes later, the cardiovascular system was flushed, the brain removed, and each hemisphere was digested. BBB disruption, expressed as counts/minute/mg protein, was compared for each hemisphere in each group by analysis of variance. BBB damage in the diatrizoate-350 group was significantly greater than that in all other groups. No significant BBB damage resulted from iohexol or ioxilan relative to normal saline.

Animals↗

Ioversol. Double-blind study of a new low osmolar contrast agent for peripheral and visceral arteriography.

The new low-osmolar contrast agent ioversol was compared with the conventional ionic contrast agent diatrizoate in 60 patients undergoing routine abdominal (21 patients) and peripheral (39 patients) arteriography. The effects on hemodynamics, various laboratory parameters, and patient comfort were evaluated. In peripheral arteriography, there was less discomfort with ioversol as well as decreased magnitude and incidence of hypotension (P less than .001) after injection. In visceral arteriography, there was no significant difference between the two agents. Overall, the incidence of ECG changes was small in both groups (ioversol 2%, diatrizoate 8%). The two media were equivalent in incidence of adverse reactions (eg, nausea, vomiting, urticaria), the effect on laboratory parameters, and in the diagnostic adequacy of the radiographs. We conclude that ioversol is safe and efficacious for peripheral and visceral arteriography. In peripheral arteriography it causes less patient discomfort and, perhaps more importantly, fewer hemodynamic alterations than diatrizoate. These differences in hemodynamic effects may be important in patients with hemodynamic instability or limited cardiovascular reserve.

Angiography↗

Contrast media-induced lipid peroxidation in the rat kidney.

Lipid peroxidation of biological membranes is often implicated in tissue injury. The authors compared the effects of ionic and nonionic contrast media (CM) on the induction of lipid peroxidation in rat kidney and its impact on renal function. Male Wistar rats weighing 200 to 230 grams were dehydrated for 24 hours and divided into 6 groups (n = 15/group). On day 0, groups 1 through 3 were injected with 25% glycerol (10 mL/kg, im) and rats from groups 4 through 6 received an equivalent amount of intramuscular saline. The next day, rats from groups 1 and 4 were injected with normal saline (10 mL/kg, iv); groups 2 and 5 received the ionic CM, diatrizoate, and groups 3 and 6 received the nonionic CM, iopromide. Each CM was tested at 10 mL/kg BW. At 24-hour intervals, 5 rats from each group were sacrificed. In rats injected with CM (diatrizoate or iopromide) alone, no changes in serum creatinine or kidney structure were demonstrated. In glycerol treated rats, a peak in serum creatinine was seen on day 2 which returned to normal level by day 4. Histologic changes included focal tubular damage and intraluminal debris. Malondialdehyde (MDA), a marker of lipid peroxidation concentration was higher than in controls (P less than 0.05). In diatrizoate-injected rats, increase in serum creatinine on day 4 was ten times higher than glycerol; severe morphological alterations in proximal tubules were noted and significant increases in renal MDA concentration were obtained (P less than .05). Iopromide (on day 4), caused a five-fold increase in serum creatinine compared with glycerol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of iopamidol and iohexol in rat lungs following experimental aspiration.

Experimental aspiration of water soluble contrast agents was performed on rats via transoral endotracheal injection. Iopamidol, iohexol and diatrizoate were the contrast agents tested. One group of rats received normal saline as a control. Adjusted lung weights were measured at 2 and 24 hours post aspiration. Radiographs were taken at 2 and 24 hours post aspiration and scored for abnormal pulmonary air space density. Diatrizoate alone demonstrated an increase in adjusted lung weights. Diatrizoate, iopamidol and iohexol showed abnormal pulmonary air space disease on radiographs at 2 hours but not at 24 hours. Histopathologic examination of rat lungs following aspiration of all three contrasts showed pulmonary vascular congestion and perivascular edema. Iopamidol showed evidence of acute cellular inflammation. Iohexol provoked a pulmonary alveolar macrophage response.

Animals↗

Assays for plasma complement activation by x-ray contrast media.

Hemolytic complement activity and a C3a radioimmunoassay (RIA) were investigated for their ability to characterize contrast media (CM) with respect to complement activation. The CM tested were commercial formulations of diatrizoate, iodamide, iothalamate, ioxaglate, iohexol, and iopamidol. When plasma was exposed to CM, the hemolytic complement activity decreased and the C3a concentration increased. The C3a assay had a larger dynamic range and therefore more ability to discriminate among the CM. Using C3a data from pooled plasma or from individual donors' plasma, nonionic iopamidol (as Isovue 300) had lower complement-activating potential (P less than .005 and P greater than .05, respectively) than all of the ionic media based on diatrizoate, iothalamate, iodamide, and ioxaglate. The ranges of mean C3a values generated by saline, nonionic CM, and ionic CM were 48 to 60, 65 to 173, and 807 to 3272 ng C3a/50 microL, respectively. Complement activation was found to correlate with osmolality (r = 0.945, all media) and with molarity (r = 0.994, diatrizoates).

Complement Activation↗