A General and Personal Perspective on Contrast Material Research

Nonionic media have substantially reduced local toxicity in animal and human studies. The impact on systemic toxicity is less clear. In the final analysis, an understanding of the pathophysiologic mechanisms that appear to play a role in the genesis of reactions invoked with ionic media will be important in understanding the reactions invoked by nonionic media. We believe that bradykinin may contribute significantly to contrast media (CM) reactions. An underlying allergic diathesis may "prime" plasmas for potentiated contact system activation with subsequent bradykinin production. Three factors have been identified in increased concentrations in the plasmas of allergics/asthmatics that potentiate contact system activity in vitro. These are: (1) an endogenous heparin-like material having functional heparin properties; (2) an endogenous heparin-like material without functional heparin properties; and (3) a complex of the plasma inhibitor alpha 2-macroglobulin, with kallikrein, a plasma contact system protease. In clinical studies, we have demonstrated that corticosteroids administered as pretreatment will diminish significantly the incidence of reactions, and that similar pretreatment will diminish the plasma concentrations of heparin-like substances without functional heparin properties. Finally, we have shown in preliminary studies that CM can inhibit angiotensin-converting enzyme, the substance having a major responsibility for in vivo bradykinin hydrolysis.