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There is increasing evidence that activation of the plasma contact system that results in the production of bradykinin plays an important role in contrast material systemic reactions. The effects of bradykinin in anaphylaxis depend on its rate of destruction and its rate of production. The highest percentage of contrast material reactions occur after intravenous injections, and the major enzyme hydrolyzing bradykinin (kininase II; angiotensin-converting enzyme) is found on pulmonary vascular endothelial surfaces. The inhibitory effects of numerous ionic and nonionic contrast material solutions on the enzyme have been determined. Additionally, the role in this inhibition of the chelators found in all commercial contrast material vials has been studied. In vitro, all such preparations combined with their chelators inhibit angiotensin-converting enzyme. Whether this inhibition plays a role in vivo remains to be established.

Rabbits pretreated with methylprednisolone acquired significant protection against an intravenous challenge of meglumine iodipamide. In comparison to controls, the pretreated rabbits showed moderate elevations of Factor XII, and rather striking elevations of C1-esterase inhibitor. Treated rabbits also showed significantly less granulocytosis. It is believed that the protective effect can be ascribed to the modulation of acute phase reactants by increased concentrations of C1-esterase inhibitor.

Since complement activation is sharply temperature-dependent, we have examined the effects of fever produced by a very small dose of endotoxin on contrast media lethality in rabbits. After the injection of 8.2 ml/kg of 52% methylglucamine iodipamide, a group of rabbits exhibiting an average temperature elevation of 1.5 degrees C had a 100% mortality rate. This was contrasted to a 30% mortality in control rabbits receiving contrast alone, and no mortality in rabbits receiving endotoxin alone. The rabbits with fever and increased mortality exhibited increased activation of serum complement. From this preliminary data it appears that caution should be observed in performing a contrast examination in a patient with endotoxemia and/or a fever.