Inactivation of Histamine in Vivo

Abstract

One of us with Gebauer-Fuelnegg 1 has previously reported on the appearance of a physiologically active substance in the blood and lymph of dogs during anaphylactic shock and on the basis of a pharmacological and chemical study 2 concluded that the active substance was apparently histamine. It was noted in this study that this active substance may be only temporarily detectable and it was concluded that it disappeared rapidly from the blood as it circulates. Various workers have noted the inactivation or detoxication of histamine in intact animals, organ perfusions, etc. (see Best and McHenry 3 , 4 for discussion and literature). None of these studies, however, provide the necessary data to enable us to compare the fate of intravenously injected histamine with that liberated during shock. We were interested, therefore, in inducing shock of varying degrees of severity by intravenous injection of histamine at different dosage levels into dogs and of studying the blood and thoracic duct lymph for its presence and disappearance and of correlating these findings with our observations in anaphylactic shock.

Dogs were anesthetized with ether and sodium barbital and freshly prepared solutions of histamine acid phosphate (1-500) injected into the femoral vein. Samples of blood and thoracic duct lymph were collected at various time intervals thereafter. These samples were kept from clotting by means of heparin, the bloods in addition were centrifuged to obtain the plasma, and then assayed for their histamine activity by intravenous injection into cats (under ether or ether and barbital anesthesia and after the preliminary administration of atropine). The essential data of these experiments are outlined in Table I.

The degree of sensitivity of the cats used was always such that samples of blood or lymph recorded as negative contained a concentration of histamine less than 1-200,000. It is therefore apparent that injected histamine disappears very rapidly from the blood stream.