In vitro histamine release induced by radiocontrast media and various chemical analogs in reactor and control subjects

The factors governing in vitro basophil histamine release induced by radiocontrast material (RCM) were evaluated by the use of two RCMs (diatrizoate and metrizamide) and three structural analogs of RCM (benzoic acid, diaminobenzoic acid, and 3-acetamidobenzoic acid) in basophil histamine-release studies. Diatrizoate was chosen because it is a commonly used RCM and is routinely administered as a hypertonic drug (958 mOsm/kg or greater). Metrizamide is a newly synthesized RCM and is routinely administered in isotonic form (approximately 280 mOsm/kg). The analogs were used in hope of identifying any structure-function relationship that might exist between RCMs and the activation of a proposed basophil membrane receptor responsible for the induction of de granulation. In addition, results in a control group of normal subjects were compared with those in a group of patients who had experienced anaphylactoid reactions to intravenous RCM. Basophils from both groups were incubated with diatrizoate and metrizamide to assess their relative sensitivity to these drugs. Both metrizamide and diatrizoate induced in vitro histamine release. Therefore hypertonicity is not an absolute requirement for RCM-induced in vitro basophil de granulation. Although there was a trend far reagents without a prosthetic group at position 5 on the benzene ring (especially 3-acetamidobenzoic acid) to induce more release of histamine than reagents with such a prosthetic group, differences between these reagents did not reach statistical significance. Therefore no clearcut structure-function relationship could be demonstrated. “Reactor” subjects released significantly-larger percents of their intracellular histamine than did “nonreactors” (p < 0.05). Degranulated cells retained their ability to exclude trypan blue, an observation suggesting that RCM-induced histamine release does not involve cell death.