Histamine and N^t-methylhistamine in the circulation during intravenous infusion of histamine in normal volunteers

Abstract

Plasma levels of histamine and N^t-methylhistamine were measured simultaneously by high performance liquid chromatography during the intravenous infusion of histamine acid phosphate in six normal volunteers. Progressive, dose-related increases in plasma histamine were noted, reaching a maximum value of 3.1±0.14 ng ml⁻¹ corresponding to a maximum infusion rate of 180 ng kg⁻¹ min⁻¹ (means±SEM). Increases in plasma histamine were accompanied by a significant dose-related fall in mean diastolic blood pressure (baseline 74.0±4.4 mm Hg falling to 60.0±3.3 mm Hg at maximum infusion rate,p<0.001) and an increase in pulse rate (baseline 76.3±2.8 beats min⁻¹ rising to 89.24 beats min⁻¹ at maximum infusion rate,p<0.05). All subjects exhibited facial flushing, the threshold plasma histamine level for this effect being 1.3±0.15 ng ml⁻¹ corresponding to an infusion rate of 60 ng kg⁻¹ min⁻¹. Elevation of plasma N^t-methylhistamine was seen in only one subject, who exhibited a level of 0.5 ng ml⁻¹ at the highest infusion rate. These results suggest that measurements of plasma N^t-methylhistamine are unlikely to provide a useful index of histamine release into the circulation.