Circulatory Collapse in Anaphylaxis and Histamine Toxicity in Mice

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Abstract
Summary: Active anaphylaxis, passive anaphylaxis and histamine were all found to cause a highly significant rise in hematocrit values over prechallenge levels in Swiss-Webster strain (CFW) mice. The rise in hematocrit values indicated a loss of intravascular fluid sufficient to lower the average blood volumes of these groups 23 to 38% within 5 min after challenge. Injecting plasma extenders, i.e., physiologic saline or 6% dextranphysiologic saline, into mice during the first hour after challenge protected them from death, except for normal mice challenged with 24.0 mg of histamine. Injection of plasma extenders into mice receiving this massive histamine challenge gave no beneficial effects whatsoever and even seemed to be deleterious. This study strongly indicates that anaphylactic and histamine death in hypersensitive mice is due to circulatory collapse which is brought about by loss of blood volume into the extravascular space and for which the animal is unable to compensate. The histamine-sensitizing factor (HSF) from B. pertussis appears either to augment the blood volume-depleting effects of anaphylactic and histamine shock or to interfere with the vascular compensatory mechanism. The increase of histamine sensitivity produced by dichloroisoproterenol (DCI) seems to have similar mechanisms.