Histamine release and pseudoallergic reactions induced by radiographic contrast media: Comparison of Angiographin®, Hexabrix® and Telebrix® using anin vivo canine model

Radiographic contrast media (RCM) in clinical use cause unwanted allergic/pseudoallergic reactions of all grades of severity. They also induce histamine release from a variety of mast cell populations, the extent of the histamine release reaction depending on both the organ and species. In this study 3 RCM, which had been previously shown to be effective histamine releasing agents with canine liver cells, were investigated using anin vivo canine model based on the clinical situation. The dogs (n=36) were randomly allocated to one of 3 treatment groups and received a bolus injection (2 ml/kg body weight) of either Angiographin®, Hexabrix® or Telebrix®. Blood pressure was monitored continuously and blood sampling, for plasma histamine measurements, was performed before and 1, 5, 10, 20 and 30 min after RCM injection. All 3 RCM caused elevated plasma histamine levels in some animals: Angiographin® 9 of 12 dogs, 0.40 ng/ml, (0–1.9 ng/ml) median (range); Hexabrix® 11/12, 0.5 ng/ml (0–3.8 ng/ml); Telebrix® 7/12, 0.4 ng/ml (0–2.0 ng/ml). Cardiovascular reactions were observed in most animals. The hypotensive reactions occurred with a maximum 30 sec after RCM application and recovery was normally observed after 1–1.5 min. The response after Angiographin® or Telebrix® was significantly greater than after Hexabrix®. Hypertensive reactions occurred later (15 min (5–25 min)) and did not differ between the groups. All 3 agents tested were able to elicit histamine release and cardiovascular reactions. In comparison to histamine release occurring after intravenous, administration of other agents, such as hypnotics, the degree of histamine release was small. However, the frequency with which it was observed suggests that histamine acts as a contributory condition in adverse reactions to RCM. The possibility of either a localized histamine release (e.g. from liver cells) or complement activation leading to histamine release must be considered.