Therapeutic efficacy of combined -receptor-antagonists on severe histamine-induced cardiovascular reactions in humans

Abstract

Histamine is a well known causal factor in a variety of clinical events and complications, especially in allergic and anaphylactoid reactions. We therefore investigated whether a dose-dependent therapeutic effect of H1+H2-antagonists (dimethindene maleate+cimetidine) could be shown in the treatment of a histamine-induced cardiovascular reactions in humans. 6 healthy male volunteers participated in a randomized single-blind crossover-study. A histamine dosage leading to a decrease of the mean arterial pressure to 60 mmHg within 2 min was continuously infused over a period of 15 min on two occasions. The volunteers received either histamine+saline or histamine+treatment first. Treatment started 3 min after the start of the histamine infusion (4 mg dimethindene maleate+200 mg cimetidine i.v.) and was repeated every 2 min until the cardiovascular baseline values were reached or 15 min were completed. Statistical analysis of the treatment effect was performed on an intraindividual basis (ANOVA) withp<0.05 In both treatment courses mean MAP decreased to about 60 mmHg. While in the saline group MAP remained at this low level during the time of histamine infusion, all volunteers quickly responded to treatment with dimethindene maleate+cimetidine. After 8 mg dimethindene maleate+400 mg cimetidine MAP reached baseline values in all volunteers (p<0.01). Mean HR increased to 119 bpm in the saline group after 3 min. Treatment with dimethindene maleate+cimetidine showed similar efficacy against histamine-induced tachycardia (p<0.01). It may thus be concluded that usual dosages of H1- and H2-receptor-antagonists are effective in the treatment of histamine-induced cardiovascular reactions.