Blood histamine levels and arteriovenous concentration differences after the intravenous administration of the basic compounds l-3 and 48/80 in the anaesthetized dog

Abstract

The effects of the i.v. administration of inulin trinicotinate-monomethochloride (L-3) on haemodynamics, airway pressure and blood histamine levels were studied in chloralose-anaesthetized dogs and compared with the effects of compound 48/80. The control arterial histamine level was 0.041 plus or minus 0.002 mug/ml (mean plus or minus SEM) as determined by a fluorometric assay. L-3 (0.15 mg/kg) released high amounts of histamine, as indicated by a peak level in arterial histamine of 0.212 plus or minus 0.027 mug/ml within 3 min, which was not futher enhanced on increasing the dosage of L-3 to 1 mg/kg. After the i.v. injection of 0.15 mg/kg of 48/80 the peak level in arterial histamine was 0.146 plus or minus 0.008 mug/ml, and the level was further markedly elevated to 0.918 plus or minus 0.068 mug/ml after the administration of 1 mg/kg of 48/80. The concomitant fall in systemic blood pressure and the rise in airway pressure can be satisfactorily explained on the basis of histamine liberation. Whereas these parameters as well as the blood histamine concentration gradually returned to control values, the heart rate remained elevated during the observation period of 2 h. The arteriovenous differences in blood histamine across various tissues and organs following L-3 and 48/80 administration indicated histamine release mainly from skin and muscle and histamine uptake by the kidney, the digestive tract and to a lesser extent the lungs. The portal-hepatic vein differences revealed no consistent changes in liver histamine balance. As regards the lungs and liver, the present results suggest a dynamic equilibrium between histamine release and uptake in these organs in the intact animal. Both, L-3 and 48/80 elicited a similar pattern of histamine release and uptake. The extreme histamine releasing capacity of 1 mg/kg of 48/80 may be explained by an additional non-selective mechanism of histamine liberation.