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Effects of a new nonionic and a conventional ionic contrast agent on coronary sinus ionized calcium and left ventricular hemodynamics in dogs.

Transient myocardial depression associated with intracoronary injections of contrast medium has been attributed to hypertonicity and to calcium binding. To further assess the importance of calcium binding, a new technique for continuous monitoring of coronary sinus ionized calcium with an intravascular calcium-selective electrode was used. With this calcium-selective electrode the effects of intracoronary injection in dogs of a conventional ionic contrast agent, sodium meglumine diatrizoate (Renografin-76), and a new nonionic agent, iohexol, were assessed and compared. Left ventricular pressure was measured with a micromanometer catheter. After bolus injection of 0.2 ml/kg body weight of Renografin-76 (n = 10), coronary sinus pCa increased by 0.27 from 2.98 +/- 0.02 to 3.25 +/- 0.03, indicating a decrease in ionized calcium from 2.0 to 1.1 mEq/liter. With iohexol (n = 9), pCa increased by only 0.05 +/- 0.01 (p less than 0.001), indicating a decrease in ionized calcium from 2.0 to 1.8 mEq/liter. Peak changes occurred approximately 6 seconds after injection. Renografin-76 caused a marked decrease in left ventricular systolic pressure (140 +/- 7 to 106 +/- 8 mm Hg) and in heart rate (122 +/- 7 to 101 +/- 5 beats/min) with an increase in end-diastolic pressure (5 +/- 1 to 12 +/- 1 mm Hg), whereas iohexol did not significantly alter these variables. Using Renografin-76 with calcium added to achieve an ionized calcium level of 2 (n = 4), 4 (n = 4) or 6 (n = 4) mEq/liter, the changes in coronary sinus pCa were abolished and the hemodynamic changes attenuated. These findings indicate that Renografin-76 results in greater myocardial depression than the new nonionic agent iohexol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of reperfusion hyperemia with myocardial contrast echocardiography.

In this study we used myocardial contrast echocardiography to evaluate reperfusion hyperemia in an open-chest canine model of temporary coronary artery occlusion. Eight dogs had coronary occluders and electromagnetic flow probes on the left circumflex coronary artery. Aortic root injections of agitated sodium diatrizoate and saline solution were used for myocardial contrast. Data were collected at baseline (n = 16), during coronary occlusion (n = 18), immediately after coronary release (n = 18), and 5 minutes after coronary artery release (n = 12). Baseline coronary flow was 23.8 +/- 5.9 ml/min, decreasing to 0 ml/min during coronary occlusion. Immediately after coronary release flow was 96.6 +/- 41 ml/min (p less than 0.001 compared with baseline), and 5 minutes after coronary release flow was 68.2 +/- 27.9 ml/min (p less than 0.001 compared with baseline). The myocardial image intensity change after injection of contrast material was 74.25 +/- 30.6 ml/min at baseline and declined to 10.4 +/- 10.9 ml/min during coronary occlusion (p less than 0.001 compared with baseline). During reperfusion hyperemia image intensity change was 102.3 +/- 33.3 ml/min (p less than 0.001 compared with occlusion, p less than 0.02 compared with baseline, p less than 0.001 compared with remote regions). Considering all observations, myocardial image intensity change after contrast injection correlated positively with coronary flow (r = 0.67, p less than 0.001). Correlations within individual dogs ranged from r = 0.70 to 0.98. We conclude that image intensity change after aortic root injection of echocardiographic contrast correlates with coronary blood flow. Objective measurements of contrast intensity reflect increases in coronary flow associated with reactive hyperemia after coronary occlusion and release.

Animals↗

Quantifying changes in regional myocardial perfusion with aortic contrast echocardiography.

We developed a technique to assess regional myocardial perfusion by quantifying echocardiographic myocardial contrast appearance and intensity after aortic root injection of an agitated diatrizoate meglumine solution. The technique was validated by comparing digitized echocardiographic contrast parameters to regional perfusion in the circumflex bed determined by calibrated Doppler flow probe and antemortem monastral blue staining. Regional perfusion was altered by circumflex stenosis, occlusion, and reactive hyperemia. Contrast effects were measured in an initial subset of six dogs by peak intensity change, time to peak intensity, maximal rate of intensity rise, and mean intensity change integrated over 1, 2, or 3 seconds after contrast appearance (MI1, MI2, MI3). MI2 and MI3 best predicted regional perfusion (r = 0.93, standard error of the estimate [SEE] 0.38 ml/gm/min for each). These findings were confirmed in a second subset of six dogs (r = 0.84, SEE = 0.70 ml/gm/min). Although there was a relatively broad standard error for the prediction of absolute perfusion for the pooled data, for individual dogs data were internally consistent so that each had r greater than 0.88 for its varied flow states. The hyperemic ratio calculated by contrast echocardiography correlated well with the Doppler value (r = 0.85). Observer and study-to-study predictive variabilities were small (SEE 0.19 to 0.32 ml/gm/min). No alterations were seen in hemodynamics or reactive hyperemia after 25 consecutive injections over a 90-minute period. Contrast echocardiography with aortic root contrast injection tracks changes in regional blood flow. This approach can assess regional coronary reserve and detect changes in regional myocardial perfusion during acute ischemia and drug intervention.

Animals↗

Injection characteristics and downstream contrast material distribution of flush aortography catheters: in vitro study.

Performance of 11 commercially available 4- and 5-F aortic flush catheters was evaluated with respect to the extent of upstream injection, catheter motion, and downstream homogeneity of a 10-, 15-, and 20-mL/sec bolus of 76% meglumine sodium diatrizoate at room temperature. Tests were made in a pulsatile aortic flow model containing circulating fluid isoviscous to blood. The injection process was recorded on videotape. Homogeneity of the contrast material bolus was determined spectrophotometrically from samples collected from the center and each of the four quadrants of the vessel lumen. Upstream contrast material injection between 1.5 and 7 cm in length emerged from all catheters; it was lowest with one of the "tennis racket" designs from one and a new spiral end-loop design (Halo) from another manufacturer. All catheters, except the most rigid and largest-caliber catheter (5.8 F) showed considerable shaft motion at the higher injection rates. Downstream contrast material mixing homogeneity was always best at the highest injection rate but altogether was better for the Halo catheter than for any other catheter tested. It is concluded that all tested 4- and 5-F aortic flush catheters show some undesirable features, but certain design modifications improve performance and comparative testing is helpful to distinguish such features.

Aortography↗

Changes in the fibrinolytic system during angiography with ionic and with nonionic contrast media.

RATIONALE AND OBJECTIVES: The purpose of the study was to evaluate and compare changes in some parameters of the fibrinolytic system caused by the use of ionic and nonionic contrast media during angiography in certain groups of patients. MATERIALS AND METHODS: Angiographic diagnostic procedures were performed in 126 patients (male and female) clinically suspected of having kidney cancer (38 patients), arteriosclerotic occlusive disease of lower extremities (44 patients), or dissection of cerebral artery (44 patients). The control group included 12 patients with clinical symptoms of the disease in whom angiographic examination excluded the presence of cerebral artery dissection or kidney cancer. Patients were randomly assigned to receive either an ionic (diatrizoate sodium) or a nonionic (iopromide) contrast medium. Immediately before and 30 minutes after administration, venous blood samples were obtained to determine select parameters of the hemostatic system. RESULTS: There were no significant differences in the fibrinolytic parameters within the control group after contrast medium administration. The nonionic contrast medium (iopromide) caused a decrease in fibrinolytic activity in the patients, unlike the controls, which was particularly pronounced among the patients undergoing renal angiography. CONCLUSION: The use of contrast media in some groups of patients led to transient changes in the fibrinolytic system. These results indicate that ionic contrast media should be used during angiographic procedures in patients at increased risk for thrombotic complications.

Angiography↗

Comparison of patient reactions and diagnostic quality for hysterosalpingography using ionic and nonionic contrast media.

RATIONALE AND OBJECTIVES: We compared adverse reactions and image quality for hysterosalpingography (HSG) performed with ionic (diatrizoate meglumine combined with iodipamide meglumine [DM + IM]) and nonionic (iohexol) contrast media. METHODS: We performed a study of 95 patients who had HSG and were randomly selected to receive DM + IM or iohexol. Patients reported episodes of abdominal pain and other adverse reactions immediately and 24 hr after the procedure and categorized severity of symptoms on a subjective scale. Two radiologists evaluated image quality for diagnosis. RESULTS: Prevalence of abdominal pain and other reactions both immediately and 24 hr after HSG was lower in patients who received iohexol than in patients who received DM + IM. Moderate or severe abdominal pain was significantly lower in the iohexol group than in the DM + IM group (p < .05). Visualization of the uterine cavity and ampullary rugae was judged excellent with both contrast media (87% with iohexol and 92% with DM + IM). CONCLUSION: Iohexol and DM + IM are excellent contrast media for use during HSG; iohexol 300 may cause fewer episodes of more severe and prolonged abdominal pain.

Abdominal Pain↗

Spiral computed tomography of the liver: contrast agent pharmacokinetics and the potential for improved hepatic enhancement.

RATIONALE AND OBJECTIVES: We conducted a prospective study of 131 patients to evaluate the contrast agent dose-response relationship for liver spiral computed tomography (CT) and to test the hypothesis that spiral CT scanning provides greater enhancement than does dynamic CT scanning. METHODS: Patients were assigned to one of two control groups (dynamic CT) or to one of five experimental groups (spiral CT). Dynamic CT patients received 150 ml and spiral CT patients received either 75, 100, or 150 ml of diatrizoate meglumine. All groups had a monophasic injection rate of 2.5 ml/sec. Hepatic enhancement was compared among experimental and control groups. RESULTS: In the experimental groups, there was a linear dose-response relationship (p < .0001) among the enhancements achieved for the three dosages. The enhancement of the last slice of liver for the spiral CT versus dynamic CT groups receiving 150 ml was significantly greater (p = .002). Peak, first liver slice, and average liver enhancement values were higher with spiral CT scanning, but the difference was not statistically significant (power > .55). CONCLUSION: Using uniphasic injection rates and identical doses of contrast agent, spiral CT scanning has the advantage of improved enhancement of the last part of the liver to be imaged.

Adult↗

Hepatic imaging with iodinated nanoparticles: a comparison with iohexol in rabbits.

RATIONALE AND OBJECTIVES: We evaluated the efficacy of a particulate computed tomography (CT) contrast agent in an animal model of focal liver disease. METHODS: Ethyl ester of diatrizoic acid (EEDA) is an iodinated (89 mg I/ml) nanoparticulate (200 nm) contrast agent intended for intravenous use that is currently undergoing preclinical testing in our laboratory. Focal liver abscesses were created in 11 New Zealand White rabbits. Iohexol and EEDA were administered to each animal on different days. CT scanning was performed at intervals following contrast agent administration. Liver and abscess enhancement were measured and compared. Dynamic imaging experiments in normal animals were also performed using both agents. RESULTS: EEDA resulted in significantly greater enhancement of the liver and liver-to-abscess contrast than did iohexol at all time points beyond 5 min at approximately 25% of the total iodine load. During dynamic imaging, liver and aortic enhancement were greater with EEDA than with iohexol, except during a 20- to 40-sec period immediately following contrast agent administration. CONCLUSION: EEDA is superior to iohexol for imaging liver abscesses. Our results suggest that liver-directed agents such as EEDA may prove to be more efficacious than currently available extracellular agents designed for liver CT scanning.

Animals↗

Contrast nephrotoxicity: predictive value of urinary enzyme markers in a rat model.

RATIONALE AND OBJECTIVES: We tested whether urinary enzymes are an accurate and useful marker of renal damage in a rat model of contrast media nephrotoxicity. METHODS: Thirty rats were pretreated with a combination of salt depletion, indomethacin, and contrast material. Alanine aminopeptidase (AAP), gamma-glutamyltranspeptidase (GGT), and N-acetyl-beta-D-glucosaminidase (NAG) were measured before and 24 hr after injection of contrast material. Enzyme concentrations were correlated with glomerular filtration rate (GFR) and histology. RESULTS: Decreasing GFR and histopathologic changes were found only in rats treated with all three variables. NAG levels increased from baseline for both diatrizoate meglumine- and ioversol-treated animals (from 83.9 +/- 48.6 to 145.5 +/- 55.4 and from 69.41 +/- 43.6 to 123.1 +/- 50.7, respectively; P < 0.05 from baseline for ioversol) and declined in other groups. GGT and AAP levels did not correlate well with structural and functional changes. CONCLUSIONS: In this model of contrast nephrotoxicity, NAG concentration appears to correlate with structural and functional changes associated with contrast media nephrotoxicity. However, the large range of baseline values makes this of dubious clinical use. AAP and GGT levels appear less helpful in detecting renal damage.

Acetylglucosaminidase↗

Urine profiles and kidney histology after intravenous injection of ionic and nonionic radiologic and magnetic resonance contrast media in normal rats.

RATIONALE AND OBJECTIVES: Previous studies showed that both high-osmolality and low-osmolality iodinated contrast media cause temporary albuminuria and enzymuria (presence of enzymes in urine) in normal rats. Whether the same is true with ionic high-osmolality and nonionic low-osmolality magnetic resonance (MR) contrast media is unknown. We studied urine profiles and histology after intravenous injection of four types of contrast media in rats with normal kidneys. METHODS: Urine profiles were monitored 4, 24, 48, and 72 hr after intravenous injection of saline, diatrizoate, iohexol, gadopentetate dimeglumine, and gadodiamide (4.59 mmol/kg of body weight) in normal rats. Each group included 20 male rats. After sacrifice, both kidneys were removed for examination by light microscopy (LM) and electron microscopy (EM). RESULTS: All four contrast agents caused a temporary (< 22 hr) increase in the excretion of albumin (2-5 times) and of cytoplasmic (30-100 times) and brush border (10-100 times) renal enzymes when compared with saline. The degree of albuminuria correlated well (r = 0.90) with the osmolality of the injected media, whereas the increased level of enzymuria was unrelated to the osmolality. No major differences in the enzymuric effects of the four agents were noted. LM revealed vacuoles in all kidneys exposed to radiologic contrast media but not in kidneys exposed to MR contrast media or saline. Slight vacuolation was revealed by EM after the use of MR contrast media, and significant vacuolation was evident via EM after the use of radiologic contrast media. No difference between ionic and nonionic media within each drug group was detected by either LM or EM. CONCLUSIONS: Transient renal effects are induced by both ionic and nonionic high-osmolality and low-osmolality radiologic and MR contrast media in normal rats. Both osmotic (e.g., albuminuria) and chemotoxic (e.g., enzymuria) mechanisms seem to be involved. From a morphologic point of view, the chemotoxic mechanisms seem to be of major importance.

Animals↗

Time-lapse quantitative computed tomography lymphography: assessing lymphatic function in vivo.

RATIONALE AND OBJECTIVES: Immobility and massage produce different local limb lymph flow rates. We studied their influence on accumulation of radiopaque nanoparticulates in regional lymph nodes of normal rabbits. METHODS: Quantitative lymphography at 10-min intervals was used to follow the transport of subcutaneous (s.c.) nanoparticulates produced from insoluble esters of diatrizoic acid. In one design, both hindpaws received 0.5 ml of nanoparticulate s.c., and one hindpaw was massaged. In a second design, one hindpaw was injected and massaged while imaging the popliteal, presacral, and paraaortic nodes every 10 min. RESULTS: Gentle massage rapidly increased popliteal node accumulation in comparison with the immobile limb. On the massaged side, mean Hounsfield (HU) units, maximum Hounsfield units, and calculated iodine were significantly greater at 10 min and all subsequent times. In the node transfer experiments, it took 12, 30, and 45 min, respectively, to obtain 100-HU mean attenuation; 200-HU maximum attenuation thresholds were achieved at 20, 47, and 69 min, respectively. CONCLUSION: Quantitative computed tomography lymphography reflects local lymph physiology. Gentle massage of the s.c. injection site is a powerful lymphotropic stimulus.

Analysis of Variance↗

Assay of radiographic contrast agents in mice plasma and testes by high-performance liquid chromatography.

A new buffer system is reported for the analysis of radiographic contrast agents (RCAs) sodium meglumine diatrizoate, iohexol, and iopamidol in mice plasma and testes, on a reversed-phase HPLC with UV detection. The buffer consisting of 0.1 M NaH2PO4, 0.2 mM Na2EDTA adjusted to pH 3.1 with orthophosphoric acid and 2.5-5.0% acetonitrile (v/v) resolved RCA peaks for clear quantitation. The main advantages of this system are the ambient temperature of operation and direct sample injection without prior sample purification as required in the earlier procedures. Using this procedure, uptake and clearance kinetics of these RCAs were studied in mice plasma and testes, following iv injections via tail veins. The plasma levels of all the RCAs reached maxima between 5 and 15 min and dropped down sharply. At the end of 12 h they were virtually undetected (detection limits 0.64-0.71 micrograms/mL). The testicular levels also showed a similar trend and reached undetectable levels after 4 h. There were no signs of metabolism of these RCAs in plasma or testes. The present clearance kinetics in plasma compares very well with earlier reports of non-HPLC methods of assay.

Animals↗

Measurement of GFR with non-radioisotopic radio contrast agents.

The clearance of creatinine has been shown to overestimate GFR in patients with renal disease and in kidney transplant recipients. Alternate means for measuring GFR involve the use of constant infusion and, frequently, of radioisotopes. We report herein the measurement of GFR with the use of a radiocontrast agent (diatrizoate meglumine) injected subcutaneously with a small amount of epinephrine (0.05 ml of 1:1000). The concentrations of this marker of glomerular filtration in blood and in urine were measured with high-performance liquid chromatography. The results demonstrate that with this method of administration stable blood levels are observed for at least three hours. Furthermore, creatinine clearance overestimated GFR by 50% and by 68% in patients with renal disease and in renal transplant recipients, respectively. This method offers several advantages: 1) the use of commonly available and inexpensive materials; 2) obviates the need for the use of constant infusions; and 3) avoids the use of radioisotopes.

Adult↗

Reduced activity of antioxidant enzymes underlies contrast media-induced renal injury in volume depletion.

Oxidant-mediated renal injury has been suggested as an important mechanism of acute renal failure induced by contrast media. Since volume depletion has been recognized as a predisposing factor for contrast media nephropathy, the present study was designed to characterize host-defense mechanisms against oxidant-mediated renal injury during volume depletion. Antioxidant enzyme activities in renal cortex were compared between acutely water deprived (WD, 72 hours) and non-WD rats. WD rats had reduced activities of catalase and superoxide dismutase activities (on average, 48% and 60% of values in non-WD, respectively). In separate groups of WD rats, saline or one of three different contrast media, namely diatrizoate meglumine/diatrizoate sodium (DTZ), ioxaglate meglumine/ioxaglate sodium (IXG), and iohexol (IHX) was injected. Both GFR and renal plasma flow rate, measured 24 hours later, was some 50% less in DTZ-injected than saline-injected WD rats. WD rats treated with IXG and IHX had similar GFR to saline-treated rats. In DTZ-treated WD rats, specific products of membrane lipid peroxidation, phosphatidylcholine and phosphatidylethanolamine hydroperoxide, determined by chemiluminescent HPLC, were more than two-fold higher than saline, IXG, or IHX-treated WD rats. DTZ did not induce renal dysfunction and enhance lipid peroxidation in non-WD rats. Therefore, DTZ appeared to induce oxidant-mediated injury only in WD rats. When WD rats were pretreated with polyethylene glycol-coupled catalase (1.4 mg x 2 days), renal cortical catalase activity remained at a level similar to that of non-WD rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The use of dilute Calogen as a fat density oral contrast medium in upper abdominal computed tomography, compared with the use of water and positive oral contrast media.

AIM: Oral contrast media are commonly given prior to computed tomography (CT) examination of the upper abdomen. Although positive oral contrast media are normally used, there is increasing interest in using negative agents such as water and less commonly fat density products. The aim of this study was to compare a positive oral contrast medium, water, and a diluted emulsion of arachis oil Calogen, a fat density food supplement) for assessment of the upper abdomen. MATERIALS AND METHODS: Seventy-one patients referred for upper abdominal CT were randomized to receive either 500 ml water, 2% sodium diatrizoate or a dilute suspension of Calogen. The CT images were scored independently by three radiologists. Distension and anatomical identification was assessed for the stomach, duodenum and jejunum; with anatomical identification recorded for the pancreas, retroperitoneum, liver, gallbladder and spleen. RESULTS: Dilute Calogen produced a significant improvement (P < 0.01) in distension and anatomical visualization of the stomach and proximal duodenum. Only minimal differences were demonstrated between the three contrast media for visualization of more distal small bowel or identification of the other upper abdominal viscera. Significantly more artifacts were caused by positive contrast media than with the Calogen mixture. CONCLUSION: A dilute suspension of Calogen as an oral contrast medium is recommended when disease is suspected within the stomach or proximal duodenum.

Artifacts↗

[Selective renal angiography with fractionated contrast medium injection. An experimental study in the dog (author's transl)].

Fractionated contrast medium was compared with the conventional technique in 96 selective renal angiograms in the dog. The only possible clinical significance might be that improved visualisation of the renal vein was obtained with this technique without increasing the total administered dose. The overall best result in this regard was obtained with 2 and 6 ml. diatrizoate 60% injected with an interval of five seconds. Compared with other vasodilators, contrast material reflux into the aorta was not reduced and the vasodilator effect on the main renal, segmental and interlobar arteries was not constant and less marked.

Angiography↗

A randomised, prospective study comparing two contrast media in ERCP.

A randomised, prospective, stratified, double blind study comparing two contrast media in endoscopic retrograde cholangio-pancreatography (ERCP) was undertaken. Forty-six patients received Meglumine/Sodium Ioxaglate (Hexabrix 320) and forty-eight received Meglumine/Sodium Diatrizoate (Urografin 310). The two groups were evenly matched for age, sex and diagnosis. Radiographs were examined independently by two radiologists. There were no differences in radiograph quality with either type of contrast medium. More patients developed pancreatitis following Urografin, suggesting that Hexabrix is a safer contrast medium for ERCP.

Adult↗

[Determination of hematocrit and iodine concentrations following intravenous bolus administration of ionic and nonionic monomeric and dimeric contrast media--an animal experimental study].

A monomeric ionic (meglumine diatrizoate), a monomeric non-ionic (iopromide) and a dimeric non-ionic contrast medium were intravenously administered (V. jugularis) to 15 rabbits. Blood iodine concentration as well as haematocrit were determined from blood samples taken from the femoral artery immediately after injection until the 90th second p.i. The contrast media showed clear differences concerning the haematocrit, i.e. the isotonic non-ionic dimer induced its lowest decrease. The direct determination of the blood iodine concentration revealed no significant deviations between the contrast media studied. Only non-ionic dimers are iso-osmolar with plasma at the iodine concentrations employed in diagnostic radiology. Compared with monomeric compounds this study provides fundamental evidence that isotonic, non-ionic dimeric contrast media cause only slight effects on blood cells. This confirms experimentally the clinically reported good tolerance of dimeric contrast media in patients.

Animals↗