Hoppe, James O.; Duprey, L.P.; Borisenok, W.A.; Bird, Joseph G.
May 1967
Angiology;May1967, Vol. 18 Issue 5, p257
Academic Journal
1. Selective radiopacity was defined as the selective diagnostic x-ray visualization of a soft tissue structure without harming the tissues with which the x-ray contrast medium comes in contact. Selective radiopacity in cardiovascular angiography with particular reference to large vessel angiography was discussed. 2. The radiopaque properties of the x-ray contrast medium in solution of primary importance to selective radiopacity in cardiovascular angiography include; (a) radiopacity, which is a function of the number of milligrams of iodine/ml of solution and determines the density of the x-ray image; (b) viscosity, which determines the ease with which the solution can be introduced into a specific vascular bed; and (c) toxicity at the systemic as well as the local tissue levels. Of these properties, the lowest possible toxicity is of greatest importance to selective radiopacity in cardiovascular angiography. 3. Progress in the search for less toxic cardiovascular angiographic media was illustrated by the more than ten-fold reduction in systemic toxicity as measured in the mouse in going from sodium iodide to the newer x-ray contrast media. 4. The newer media, sodium iothalamate, sodium metrizoate and sodium iodamide are more water soluble than sodium diatrizoate. None of these compounds appear to offer any significant improvement over sodium diatrizoate with respect to systemic toxicity. 5. The currently available cardiovascular contrast media, in solution at the pH of the plasma, dissociate almost completely into a radiopaque anion and a water-solubilizing or non-radiopaque cation. Both ions influence the radiopaque properties of the x-ray contrast medium in solution. The radiopaque moiety of diatrizoic, iothalamic, metrizoic and iodamide acids provide radiopaque anions of low toxicity. Of the sodium and N-methylglucammonium cations which are commonly used to form water soluble salts, the sodium salt is a more efficient radiopaque and provides solutions of higher radiopacity and lower viscosity. Concentrations of the sodium salt above 50% were associated with the appearance of adverse local tissue effects on the blood-brain barrier of the rabbit. The meglumine salt, on the other hand, is better tolerated u])on direct intra-arterial injection into sensitive vascular beds while limitations on its use at concentrations above 60% become apparent because of viscosity. 6. The greater radiopacity of sodium diatrizoate and the greater water solubility of meglumine diatrizoate have long been combined to provide formulations of increased radiopacity for large vessel angiography. A comparison of the acute intravenous toxicity of meglumine diatrizoate and sodium diatrizoate alone, and as a mixture of meglumine and sodium salts in a ratio of 2:1 in Hypaque-M, 75% and Hypaque-M, 90%, in the mouse, rat and rabbit, indicated less variation in toxicity among these species with the mixtures of the two salts than with the individual salts alone. 7. A solution of 75% sodium metrizoate or 80% sodium iothalamate contains the equivalent of some seven to eight times the plasma concentration of sodium. Since this excess of sodium in relation to tho other extracellular cations is reminiscent of the Ringer's solution concept, it was of interest to find that formulation of metrizoic acid as a mixture of the sodium and meglumine salts, along with the addition of calcium and magnesium in proportion to their plasma concentrations, resulted in a reduction in acute systemic toxicity in comparison with that of sodium metrizoate alone. Isopaque 440, a balanced ion formulation containing 47% sodium metrizoate, 2.5% calcium metrizoate, 0.8% magnesium metrizoate and 32% meglumine metrizoate was found to be significantly less toxic than sodium metrizoate by intravenous injection in the mouse, rat and rabbit. 8. The radiopaquo properties of Isopaque 440 indicate a radiopacity similar to that of Hypaque-M, 90% and Angio-Conray, 80%; a viscosity half that of Hypaque-M, 90% and similar to that of Angio-Conray, 80%; and a systemic toxicity in the mouse, rat and rabbit similar to that of Hypaque-M, 90%, and significantly less than that of Angio-Conray, 80%. 9. The data on Isopaque 440 indicate that it is possible to utilize both the sodium and meglumine salts of metrizoic acid with the acid of calcium and magnesium salts to formulate a new balanced ion cardiovascular angiographic x-ray contrast solution with high radiopacity, low viscosity and low toxicity for large vessel angiography and angiocardiography.


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