Concentration effect relationships of infused histamine in normal volunteers

Histamine was infused in six normal volunteers at rates of 16, 32, 64 and 96 ng/kg/min increasing at 5-min intervals followed by 128 ng/kg/min for 45 min. Heart rate increased, diastolic blood pressure decreased and skin temperature increased in a dose-dependent fashion. Mean heart rate increased by 15.6 +/- 5.7 beats/min, mean diastolic pressure fell by 8.8 +/- e.2 mmHg and mean skin temperature increased by 1.2 +/- 0.3 degrees C at the highest infusion rate. Mean plasma histamine rose from a basal level of 0.20 +/- 0.03 ng/ml to 1.97 +/- 0.25 ng/ml at the end of the highest infusion rate. The threshold infusion rate for physiological effects was 64-96 ng/kg/min corresponding to 0.77-0.97 ng/ml. Salivary flow was stimulated by 21% after 30 min at the highest dose infusion (P = 0.05). Plasma adrenaline increased 132% but plasma noradrenaline was unchanged. There was a linear decline in heart rate after terminating the histamine infusion with a half time of 82 sec. The half life of infused histamine in the plasma was 102 sec. The clearance of histamine from the plasma was 6.1 %/- 0.2 l/min or 83 ml/kg/min. These concentration effect relationships in normals throw doubt on some of the high endogenous plasma histamine values in the literature.