Combined Action of Potassium and Histamine on Mice and Guinea Pigs

¹ From the Naval Medical Research Institute, National Naval Medical Center, Bethesda, Maryland

When body cells are damaged by force, burns, lack of oxygen or decreased blood supply, they release substances which in large enough quantities induce shock often resulting in death. Two of these substances have been identified as histamine and potassium. Either of these when injected into normal intact animals can induce shock and death. The lethal dose curves for each of the two agents when given in solution intraperitoneally to mice and to guinea pigs were determined. Potassium toxicity was quite comparable in both species, but histamine resistance in mice was more than 100 times that of guinea pigs. When both histamine and potassium are combined in a single injection the mortality rate goes up. The addition of a small amount of one will increase the toxicity of a known amount of the other to a point much greater than the sum of each given separately. A variety of combinations of both were tested in about 1600 mice and about 500 guinea pigs. The results suggest that in future studies of traumatic and anaphylactic shock, the simultaneous blood levels of both substances should be determined. Further experiments gave evidence that enhancement of toxicity diminished when the two agents were injected separately and that a plasma potassium rise did not follow histamine injection in all species. Glutathione which has been shown to protect against potassium, also had a protective action in mice against the histamine-potassium combination. An antihistaminic (Chlor-Trimeton) which protected guinea pigs against histamine alone did not protect them or mice against the combination.