Prevention of canine anaphylaxis with isoproterenol

Sympathomimetic agents are used to reverse the cardiovascular and respiratory abnormalities that are associated with anaphylactic shock. In addition, in vitro studies have demonstrated that beta-adrenergic stimulation modulates IgE-mediated release of chemical mediators. To separately evaluate the ability of isoproterenol, a beta-adrenergic agonist, to prevent mediator release and anaphylactic shock, as well as to reverse the cardiopulmonary manifestations of systemic anaphylaxis, we administered a continuous infusion of isoproterenol before and during canine anaphylactic shock. An intravenous injection of Ascaris suum antigen was used to produce shock, which was characterized by a 50 ± 15% (mean ± SEM) decrease in mean arterial blood pressure, a 30 ± 8% decrease in cardiac output, and a 122 ± 95% increase in total pulmonary resistance. These changes were associated with significant increases in plasma histamine concentrations from 1.1 ± 0.1 to 158.4 ± 137 ng/ml. Administration of a continuous infusion of isoproterenol during anaphylactic shock did not significantly improve any of these physiologic abnormalities. However, when isoproterenol was administered prior to the injection of antigen, these physiologic changes were prevented and histamine release was inhibited in a significant proportion of animals. In contrast, beta-adrenergic stimulation did not prevent nonimmunologic shock and mediator release induced with compound 48/80. We conclude that the administration of a beta-adrenergic agonist prevented the cardiopulmonary manifestations of anaphylactic shock by inhibiting mediator release and that the physiologic effects of isoproterenol administered during systemic anaphylaxis were minimal.