Chronic Histamine Action. ∗

Abstract

Histamine placed in the body in watery solution rapidly produces acute effects of relatively short duration (Dale and Laidlaw 1 ). During the past 2 years studies have been undertaken to develop a procedure by which injected histamine would act over prolonged periods and produce chronic effects. The ultimate aim of the investigation was the study of chronic histamine poisoning.

Experimental Procedure. Histamine was administered by subcutaneous or intramuscular injection. All doses mentioned are in terms of histamine base. Two tests were employed to determine the efficacy of the methods used to slow the rate of absorption of histamine from the sites of injection. The first was a comparison in normal guinea pigs of the effects of large doses of histamine in saline solution with the effects of the same dose of histamine in other substances. While this method was satisfactory for the preliminary experiments it was inadequate for the quantitative determination of the extent and degree of prolonged histamine action. The second test was the measurement of the amount and quality of the secretion from gastric pouches of dogs made according to the method of Heidenhain. This test provided a quantitative basis for studying the extended action of histamine. The pouches were prepared under ether or nembutal anaesthesia using the usual surgical technic and sufficient time for recovery was allowed before tests were commenced.

Histamine was first ground with glycol stearate and then suspended in mineral oil. In guinea pigs, injection of this material was quickly followed by typical symptoms and fatalities. Similar results were obtained when histamine particles were covered with paraffin and suspended in oil. Definite protection was obtained with a mixture of finely powdered histamine, pure beeswax or beeswax containing resin and mineral oil.