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PubMed1991

Selective injection of contrast media: inflammatory effects on rabbit fallopian tubes.

The inflammatory effects of fallopian tube catheterization and selective injection of seven contrast agents (ethiodized oil, diatrizoate meglumine 52%, diatrizoate meglumine 66%, iothalamate meglumine 60%, iopamidol, ioxitol, and ioxaglate) were evaluated in 88 rabbits. The contrast agent used was randomly selected and selectively injected after unilateral catheterization; the contralateral side was used for control. Pathologic inspection of right and left uteri with attached fallopian tubes and ovaries was done without knowledge of side of catheterization or duration of time since catheterization. The degree and location of inflammation were noted. Inflammation disappeared by 4 days in five of seven contrast agents. Iothalamate meglumine 60% and iopamidol required 2 weeks for disappearance of inflammation. Essentially no inflammation was associated at any time with ioxaglate. These findings suggest that all of these contrast agents would be clinically acceptable for direct injection into the human fallopian tube.

Animals↗
PubMed1992

Diagnostic efficacy of excretory urography with low-dose, nonionic contrast media.

A prospective, randomized, physician-blinded study was conducted to determine whether a smaller dose of low-osmolar, nonionic contrast medium can provide diagnostic information on excretory urograms equivalent to that obtained with higher doses of ionic and nonionic contrast agents. One hundred fifty adult patients who underwent excretory urography received a high-dose ionic contrast medium (diatrizoate sodium), high-dose nonionic contrast medium (iohexol), or low-dose nonionic contrast medium (iohexol). All urograms were scored for diagnostic quality. No difference in urographic quality was detected among the different doses of contrast media. The lower dose of low-osmolar nonionic contrast medium provided equivalent diagnostic information. The quality of the nephrotomograms, ureteral image, and overall image was slightly greater with diatrizoate than with a small dose of iohexol, but the difference was not significant. This study suggests that excretory urograms obtained in relatively healthy, well-prepared patients with smaller, less expensive doses of a nonionic contrast agent are at least diagnostically equivalent to those obtained with typical higher doses of ionic and nonionic agents.

Contrast Media↗
PubMed1995

Nephrotoxicity from contrast media: attenuation with theophylline.

PURPOSE: To determine if depression of creatinine clearance after administration of contrast medium may be prevented with theophylline. MATERIALS AND METHODS: A nonionic, low-osmolality contrast medium (iopamidol) or an ionic, high-osmolality contrast medium (sodium diatrizoate) was administered to 93 patients. Before the examination, these patients were given theophylline or a placebo orally. There were also 30 patients who received an adenosine-uptake inhibitor (dipyridamole). Creatinine clearance and urinary adenosine levels were measured before and after angiography. RESULTS: Creatinine clearance decreased 18% +/- 4 in the placebo-iopamidol group but did not decrease in the theophylline group; urinary adenosine increased 67% +/- 7. Creatinine clearance decreased 42% +/- 5 in the placebo-sodium diatrizoate group and decreased 24% +/- 3 in the theophylline group; urinary adenosine increased 119% +/- 8. In the dipyridamole group in which iopamidol was given, urinary adenosine increased 96% +/- 7 and creatinine clearance decreased 37% +/- 5. CONCLUSION: Intrarenal adenosine can be implicated in the pathogenesis of hypertonic contrast medium nephrotoxicity.

Adenosine↗
PubMed1995

Bosentan, an orally active endothelin antagonist: effect on the renal response to contrast media.

PURPOSE: To examine the effect of bosentan, an orally active endothelin-receptor antagonist, on the renal response to contrast media in the isolated perfused rat kidney (IPRK) and to establish whether bosentan can inhibit contrast media-induced nephrotoxicity in a multiple-insult model in the conscious rat. MATERIALS AND METHODS: Renal function was measured in the IPRK (n = 24) and in the rats that had undergone unilateral nephrectomy, were maintained on a salt-free diet, and were receiving indomethacin (10 mg/kg/d; n = 60). RESULTS: In the IPRK, diatrizoate and iotrolan reduced the glomerular filtration rate and renal perfusate flow, an effect markedly inhibited by bosentan (n = 6 per group). In the multiple-insult rat model, the fall in creatinine clearance produced by diatrizoate was also markedly inhibited by bosentan (n = 15 per group). CONCLUSION: Endothelin antagonists such as bosentan may be used to reduce the prevalence of contrast-induced nephrotoxicity.

Administration, Oral↗
PubMed1984

Role of ischemia in contrast-induced renal damage: an experimental study.

Total and regional cortical blood flow was measured in dogs by the radioactive microsphere technique after renal damage of varying severity had been induced by combining selective injection of diatrizoate, iopamidol, or normal saline with a 10 min occlusion of the renal artery. There was extensive tubular and glomerular damage in the kidneys exposed to diatrizoate, but not in the kidneys exposed to saline. Iopamidol caused intermediate changes. Average cortical blood flow was reduced from baseline levels in all groups 5 min after perfusion was restored. After 1 hr the flow had returned to the baseline level. Analysis of variance did not show a statistically significant difference among the groups. A tendency for redistribution of flow from outer to inner cortical layers was seen, but this was present in all groups. The flow changes detected in this study cannot explain the varying severity of renal damage.

Animals↗
PubMed1985

Transluminal, subselective measurement of coronary artery blood flow velocity and vasodilator reserve in man.

Assessment of coronary blood flow and the vasodilator reserve capacity of individual coronary arteries in the catheterization laboratory has been hampered by methodologic limitations. We have developed and validated a small Doppler catheter that can subselectively measure phasic coronary blood flow velocity (CBFV). In seven anesthetized calves, CBFV was varied from 0.1 to 5.7 times control CBFV. Changes in mean CBFV measured intraluminally by catheter in the left anterior descending and left circumflex arteries were similar to those measured simultaneously with an epicardial Doppler probe on the surface of the same vessel (n = 85, r = .95, slope = 1.04) and to changes in coronary sinus flow (n = 69, r = .97, slope = 1.06) measured with timed venous collections. Identical maximal coronary reactive hyperemic responses with the catheter present and absent in the artery being studied demonstrated that coronary obstruction by the catheter was minimal. Safety studies in six additional calves demonstrated that the catheter caused small changes in coronary endothelial permeability. Histologic studies revealed no endothelial denudation or thrombus formation. Stable phasic recordings of coronary blood flow velocity have been obtained in 58 of 70 patients studied. One of the 70 patients studied had abrupt coronary occlusion probably related to catheter-induced vasospasm. In 10 normal patients, intracoronary meglumine diatrizoate increased CBFV to 3.5 times that at rest (range 2.8 to 5.0). CBFV rose 5.0-fold after an intravenous infusion of dipyridamole (range 3.8 to 7.0). In each patient, dipyridamole produced greater vasodilation than meglumine diatrizoate. The time- and dose-response characteristics to dipyridamole infusion were heterogeneous, underscoring the advantage of continuous on-line measurement of CBFV in the measurement of vasodilator reserve. This method of measuring CBFV and assessing vasodilator reserve in the catheterization laboratory should facilitate studies of the coronary circulation in man.

Animals↗
PubMed1994

A comparison of low- with high-osmolality contrast agents in cardiac angiography. Identification of criteria for selective use.

BACKGROUND: Controversy exists as to whether low-osmolality radiographic contrast agents, which have less detrimental pharmacological effects but are considerably more expensive than high-osmolality agents, should be used universally or only for selected high-risk patients. METHODS AND RESULTS: A randomized, double-blind study was used to compare the frequency and severity of adverse events in 2245 consecutive patients undergoing diagnostic cardiac angiography. Two thousand one hundred sixty-six patients were successfully randomized to either iohexol, a low-osmolality contrast agent, or diatrizoate (as Hypaque 76), a high-osmolality agent. The end point event included clinically important adverse events (which jeopardized the patient or required aggressive treatment), contrast agent-related procedure abbreviations, and conversion to open-label contrast agent. Clinically important end point events were associated with increased age, New York Heart Association functional class, left ventricular end-diastolic pressure, arteriovenous oxygen difference, severity of coronary artery disease, and history of a previous reaction to contrast agent. End point events were less frequent in patients receiving iohexol (2.6% versus 4.6%; adjusted odds ratio, 1.59; 95% confidence interval, 0.97-2.60; P = .07). The difference in event frequency between iohexol and diatrizoate was confined to the highest-risk quartile of the patient population. An algorithm was developed to classify patients as being at high or low risk for an event based on patient age, New York Heart Association class, history of a prior contrast reaction, and left ventricular end-diastolic pressure. Application of this algorithm for selective use of low-osmolality agents only for high-risk patients to a theoretical population of 1000 patients reduced contrast agent costs 66% without increasing the frequency of contrast agent-related adverse events. CONCLUSIONS: The advantages of low-osmolality contrast agents are clinically important in patients with severe heart disease but are not in less ill patients. Universal use of low-osmolality agents for cardiac angiography in an unselected population is not necessary. Appropriately guided selective use of low-osmolality contrast agents is feasible and has the potential to reduce cost substantially without compromising safety or effectiveness.

Algorithms↗
PubMedDate not supplied

Acute effect of angiographic contrast medium on cortical specific gravity after middle cerebral artery occlusion in rats.

Early angiography after cerebral arterial occlusion has been cited as potentially detrimental. This investigation evaluates the effect of acute angiographic contrast medium administration on the cortical edema induced by middle cerebral artery (MCA) occlusion. Sixteen rats underwent MCA occlusion, and after 1 hour half the rats underwent ipsilateral internal carotid injection of meglumine diatrizoate, whereas the remainder underwent cervical internal carotid exposure only. Six rats had only sham operations on the MCA and internal carotid, and 4 other rats served as normal controls. Cortical specific gravity was measured to reflect cerebral edema 4 hours after occlusion or sham operation. Specific gravity of the lateral frontal cortex in the hemisphere ipsilateral to occlusion was 1.0396 +/- 0.0011 (mean +/- SEM) when no angiographic contrast medium was administered, significantly less (p less than 0.01) than in rats exposed to contrast medium (specific gravity 1.0442 +/- 0.0005). The latter value was not significantly different from normal. Other cortical areas on the side of the contrast medium injection were also relatively dehydrated compared with normal controls. Early meglumine diatrizoate administration after MCA occlusion results in a decrease in cerebral cortical edema, possible by inducing an osmotic gradient that draws water from the extravascular space.

Animals↗
PubMed1991

The use of ionic and nonionic contrast agents and the effects of hydration in the post cardiac transplant patient with moderate renal insufficiency.

To determine the effects of ionic (diatrizoate) and nonionic (iopamidol) contrast and of hydration, 90 asymptomatic cyclosporine-treated cardiac transplant patients with moderate renal insufficiency (serum creatinine greater than or equal to 1.5 mg/dL) undergoing cardiac catheterization were evaluated. All patients were hydrated with intravenous fluid (5% dextrose and 0.5 normal saline) over a twelve-hour period prior to catheterization and with oral fluids thereafter. Thirty patients received iopamidol (Group I) and 60 were given diatrizoate (Group II). Renal function was determined the day before and after catheterization in all patients of Group I and in 30 patients of Group II (Group IIa). In the remaining 30 patients of Group II renal function was also determined before contrast administration (Group IIb). The dose of dye was similar in all groups (I: 139 +/- 55 mL, IIa: 140 +/- 58 mL, IIb: 128 +/- 38 mL). There was a significant decrease in BUN (I: 41 +/- 10 to 33 +/- 8 mg/dL [p less than 0.005], IIa: 42 +/- 9 to 33 +/- 8 mg/dL mg/dL [p less than 0.001], IIb: (44 +/- 12 to 34 +/- 10 mg/dL [p less than 0.005]) and a small decrease in serum cratinine after catheterization (I: 2.0 +/- 0.3 to 1.9 +/- 0.3 mg/dL, IId: 2.0 +/- 0.3 to 1.9 +/- 0.3 mg/dL, IIb: 2.1 +/- 0.4 to 1.8 +/- 0.4 mg/dL [p less than 0.005].(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Urea Nitrogen↗
PubMed1978

Effect of ionic and non-ionic contrast media on morphology of human erythrocytes.

The effects of solutions of the ionic contrast media diatrizoate, iocarmate and metrizoate and the non-ionic metrizamide on red cell morphology were compared by interference contrast optics in vitro. All the media produced changes, in solutions both isotonic and hypertonic to blood. The changes increased with increasing volume ratio (contrast medium/blood). At low volume ratio the cells were transformed into crenated cells (echinocytes) in ionic solutions both hypertonic and isotonic to blood. At high volume ratio the hypertonic ionic media caused the red cells to become shrunken (desiccocytes), corresponding to the shrinkage caused by hypertonic saline. The low osmotic non-ionic metrizamide never produced desiccocytes but echinocytes also in high volume ratio. In solutions isotonic with blood metrizoate and metrizamide transformed more cells into echinocytes than the diatrizoate and iocarmate solutions.

Contrast Media↗
PubMed1978

Effect of metrizamide on whole blood oxygen affinity.

The effects on whole blood oxygen affinity following addition to human blood of either ionic (diatrizoate) or non-ionic (metrizamide) contrast medium were investigated in vitro. No medium changed whole blood oxygen affinity. Solutions of metrizamide produced less changes in plasma pH than solutions of diatrizoate. This difference is explained by lower buffer capacity and lower osmolality of metrizamide solutions. Low osmolality gives less redistribution of anions between plasma and red cells and therefore less decrease in plasma pH.

Diatrizoate↗
PubMed1978

Effect of ionic and non-ionic contrast media on red cell aggregation in vitro.

The effect of solutions of the ionic contrast media diatrizoate, iocarmate, and metrizoate and the non-ionic metrizamide on red cell aggregation in vitro was examined. The aggregation was recorded by both microphotography and photometry in a counter-rotating rheoscope chamber. All the contrast media decreased the formation of red cell aggregates. This desaggregating ability increased with both increasing volume ratio (contrast media/blood) and with increasing osmolality of the contrast media. The desaggregating effect was also obtained with the contrast media solutions isotonic with blood. The iocarmate and diatrizoate solutions induced less reduction in red cell aggregation than the metrizoate and metrizamide solutions.

Contrast Media↗
PubMed1983

Effects of ioxaglic acid on cardiac functions during coronary arteriography in canines.

The new monoacid dimer ioxaglic acid (P286), The non-ionic metrizamide (Amipaque) and diatrizoate (Renografin 76) were compared regarding their effects on left ventricular pressure, the first derivative of left ventricular pressure, aortic pressures and on ECG changes during left and right coronary angiography in dogs. Ioxaglate was found to affect most of these parameters less than diatrizoate probably due to its lower osmolality. Ioxaglate should be regarded suitable for coronary angiography. However, ioxaglate was found to have greater effects on the cardiac function than the equiosmolar metrizamide. This is probably due to the chemotoxicity of the anion or possibly to the sodium content of the ioxaglic acid solution.

Angiography↗
PubMedDate not supplied

Renal function following nephroangiography with metrizamide and iohexol. Effects on renal blood flow, glomerular permeability and filtration rate and diuresis in dogs.

The non-ionic ratio 3.0 contrast media metrizamide and iohexol used in high-dose unilateral nephroangiography in dogs produce homogeneous nephrograms and no marked effects on renal blood flow, glomerular filtration rate, and osmotic diuresis, in contrast to previously reported results using the same technique with iodine-equivalent doses of the ionic ratio 1.5 contrast medium diatrizoate (25). Iohexol affected glomerular permeability significantly less than metrizamide and diatrizoate.

Albuminuria↗
PubMedDate not supplied

Effect of contrast media on the formation of prostacyclin in isolated rat lungs.

The synthesis of prostacyclin (PGI2) was studied in isolated perfused rat lungs during the infusion of radiographic contrast media into the pulmonary circulation. At the same molar concentration, diatrizoate, iopamidol, and NaCl fairly equally stimulated the generation of PGI2. A bolus injection of histamine also enhanced the formation of PGI2. A high dose of ionic diatrizoate and hypertonic saline (0.4 mol/l) caused considerable pulmonary edema, which was less marked with non-ionic iopamidol. Experiments with 125I-labeled contrast media indicated rapid efflux of contrast media from the lungs. The present investigation indicates that different contrast media stimulate the synthesis of prostacyclin mainly because of chemical irritation of the pulmonary endothelium. The enhanced formation of endothelium-derived prostacyclin may mediate some systemic and local side effects seen temporarily during intravascular contrast medium examinations.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Studies on the in vitro cytotoxic effect of amiodarone.

Amiodarone, a potent antiarrhythmic drug, contains 37.2% iodine by weight and may induce either hypo- or hyperthyroidism. The high iodine content of amiodarone may be responsible for both complications, but a cytotoxic effect of the drug on the thyroid resulting in thyroiditis has been reported. In the present study the cytotoxic effect of amiodarone was evaluated in three culture systems with different biological properties: 1) a strain of rat thyroid cells (FRTL-5 cells) that maintains most differentiated functions of normal thyroid cells, including an active iodide pump, but an inability to organify iodide; 2) a line of Chinese hamster ovary (CHO) fibroblasts; and 3) freshly prepared primary cultures of human thyroid follicles (hTF) that trap and organify iodide. Cells were radiolabeled with 51Cr and incubated for 24 h with medium alone, medium plus amiodarone (3.75-200 microM), medium plus an iodinated radiographic contrast agent (sodium diatrizoate; 7.5-200 microM), or medium plus potassium iodide (7.5-300 microM). At concentrations ranging from 75-200 microM, amiodarone induced a significant and dose-dependent release of 51Cr in FRTL-5 cells. In contrast, diatrizoate or KI had no cytotoxic effect on FRTL-5 cells. In the same molar concentrations, amiodarone was also cytotoxic in CHO cells. In hTF, the release of 51Cr produced by amiodarone occurred at a lower concentration (37.5 vs. 75 microM) and was significantly greater than that in FRTL-5 cells. The cytotoxic effect of amiodarone in hTF was partially, but significantly, reduced by methimazole, an inhibitor of iodide organification. In the FRTL-5 cell culture system, amiodarone also produced a dramatic inhibition of TSH-stimulated cell growth. This growth-inhibiting effect of amiodarone was evident at low concentrations (3.75-7.5 mumol/liter) of the drug, which did not produce significant cytotoxicity. In conclusion, 1) amiodarone had a cytotoxic effect in CHO fibroblasts, a nonthyroid cell line; 2) this cytotoxic effect occurred in thyroid cells independent of their ability to organify iodide; 3) however, the toxic effect of amiodarone was greater and occurred at a lower molar concentration in freshly prepared human thyroid follicles that trap and organify iodide; and 4) in the latter culture system, methimazole, an inhibitor of iodide organification, partially, but significantly, reduced the cytotoxic effect of amiodarone. These data suggest that thyroid cytotoxicity produced by amiodarone is mainly due to a direct effect of the drug on thyroid cells, but excess iodide released from the drug may contribute to its toxic action.

Amiodarone↗
PubMed1985

Comparative neurotoxicity of angiographic contrast media.

The neurotoxic effects in cerebral angiography of three iodinated ionic contrast media, nonionic iopamidol, 25% mannitol, and saline controls were compared in 25 rabbits. Diatrizoate sodium meglumine was the most toxic agent, followed by diatrizoate and meglumine, iothalamate meglumine, and mannitol in terms of blood-brain barrier (BBB) disruption and coupled perfusion decline. HIPDm distribution was more sensitive than trypan blue extravasation for monitoring brain dysfunction. Iopamidol and saline controls exhibited no visual BBB breakdown or alteration in regional uptake of I-125 HIPDm, confirming the safety of nonionic iopamidol as compared with presently used ionic contrast media.

Animals↗
PubMed1992

Vasoconstriction by angiographic contrast media in isolated canine arteries.

To study the mechanism of the pain produced by contrast media (CM) in peripheral arteriography, we examined the direct effects of low concentrations (1.85-100 mg I/ml) of CM (diatrizoate, iopamidol, ioxaglate, and iotrolan) on helically cut strips of canine blood vessels taken from six different regions. We found that: (a) low concentrations of CM induced vasoconstriction. (b) This occurred immediately after the application of CM and produced sustained constriction. (c) The constriction produced in arteries was dose-dependent. (d) The production and intensity of constriction in the arterial strips differed as follows: cranial mesenteric artery > renal artery > femoral artery > common carotid artery > thoracic aorta > coronary artery. The effects of the CM were, in order of magnitude: diatrizoate > iopamidol > ioxaglate > iotrolan. Differences between CM corresponded with the differences in osmolality of the CM solutions. (e) Low concentrations of meglumine and mannitol also produced vasoconstriction. (f) Constriction caused by all drug samples used was reversible, but the process of relaxation to the original tension was much slower in CM-treated arterial strips than in the other strips. From these results, we confirmed that the incidence and degree of vasoconstriction produced by all drug samples used in this experiment depended on solution osmolality, rather than on chemotoxicity or ionicity. We discuss the physiological mechanism of these results and stress the importance of CM hyperosmolality in vasoconstriction and vascular pain production.

Animals↗