Basic mechanisms of contrast media reactions. Theoretical and experimental considerations.

Abstract

In a broad sense the basic mechanisms that underlie reactions to injections of roentgen contrast media can be considered in two major categories: (a) allergic or idiosyncratic and (b) chemotoxic. It is the purpose of this article to examine pertinent features within each of these categories and to highlight the findings of salient studies carried out in this institution. Allergic or Idiosyncratic Considerations The term “allergic response” has been used in conjunction with altered reactions to contrast media for many years. This is unfortunate since it carries with it the connotation that the radiopaque media function as haptens, producing antibodies by combining with body proteins. Evidence against this concept has been cited by Sandström (1), Knoefel (2), and Mann(3). Their arguments include the following: 1. Drug allergy is supposed to be an acquired condition caused by an earlier administration of the same substance. Yet adverse reactions frequently occur in individuals with no previous exposure to the contrast material. 2. The incidence of abnormal reactions is not greater among those with previous exposures. 3. It seems unlikely that the radiopaque agents would function as haptens since they are chemically not very reactive. On the other hand, while conflicting reports may be cited (1, 3–6), the weight of clinical evidence suggests that contrast media reactions are more likely to occur in individuals with a history of clinical allergy. Mann (3), who believes that the contrast media function as histamine-releasing agents, notes that allergic patients have a higher content of histamine than normal in their sensitive organs. We have recently reviewed the available English language literature on this subject. Not a single instance of a demonstrated antibody against contrast media can be found in this literature. Several years ago we undertook an experimental study designed to examine this question in greater detail. White New Zealand rabbits were injected both subcutaneously and intravenously with sodium acetrizoate (Urokon) at appropriate intervals. Other rabbits were injected with an antigen composed of an acetrizoate analog (3-NH2-2,4,6-triiodo-benzoic acid) coupled by diazotization to rabbit serum albumin. For the intra-venous injections the antigen was dissolved in saline, and for the subcutaneous injections it was combined with a suitable adjuvant. The sera of these animals were examined at suitable intervals for evidence of antibody to either Urokon alone or the diazotized compound. Several different technics were utilized (capillary precipitation, Ouchterlony plate, equilibrium dialysis). No antibodies were found in the animals injected with Urokon alone, and only very weak antibodies for the conjugated preparation (7). The literature contains conflicting reports regarding the role that hypersensitivity to iodides per se might play in contrast media reactions (1, 8–10).