Histamine has long been considered to be an important chemical mediator in the pathogenesis of immediate hypersensitivity reactions. We evaluated the efficacy of antihistamines to determine the physiological role of histamine in canine anaphylaxis. Either a saline vehicle (control group), an H1 antihistamine (chlorpheniramine, 10 mg/kg), or this H1 antihistamine and an H2 antihistamine (cimetidine, 30 mg/kg) was administered to three separate groups of anesthetized dogs (n = 8). Cardiopulmonary responses and plasma histamine levels were measured after the separate intravenous injection of Ascaris suum antigen and histamine. Results were analyzed only from the animals demonstrating physiological responses or histamine release after antigen injection. In the control group, antigen produced a 43 ± 15% (mean ± SE) decrease in mean arterial blood pressure, a 34 ± 13% fall in cardiac output, and a 19 ± 9% decrease in lung compliance, whereas pulmonary vascular resistance increased 161 ± 87% and airway resistance rose 114 ± 66%. Similar physiological abnormalities were observed with histamine shock. However, peak plasma histamine levels were in most cases, greater after histamine injection than after antigen injection. An H1 antihistamine alone or in combination with an H2 antihistamine did not alter the physiological changes associated with systemic anaphylaxis. In contrast, the combined use of H1 and H2 antihistamines prevented the cardiopulmonary responses associated with the intravenous administration of histamine. These experimental results suggest that the physiological changes associated with canine anaphylaxis are due to either high local tissue levels of histamine that are not blocked by the tissue concentrations achieved by administered antihistamines or the presence of other mediators that are more important than histamine in this acute hypersensitivity reaction.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of applied physiology|
|State||Published - Jan 1 1988|
ASJC Scopus subject areas
- Physiology (medical)