Vasoactive Mediators as the "trigger Mechanism" of Endotoxin Shock.

The mechanisms by which endotoxin induces a profound shock state have not been clearly established. Several neurohumoral agents have been implicated as mediators of endotoxin shock. These include histamine (1-4), catecholamines (5-7), and serotonin (7-9). Inferences of the role played by any of these mediators have been derived from four types of evidence: a) the hemodynamic alterations observed in endotoxemia are simulated by vascular effects of the naturally occurring substance (4, 5), b) plasma concentrations of the neurohumoral agent undergo changes in endotoxin shock (7, 10-13), c) vascular reactivity to the agent is altered in endotoxemia (5, 6, 14), and d) pharmacological antagonists to the substance in question prevent certain responses to endotoxin (4, 15-17). That a primary role could be assigned to any single substance in endotoxin shock is doubtful, however, because of the complexity of endotoxemia and the frequently conflicting and occasionally inconclusive nature of the evidence (18). Our investigation was prompted by the uncertainties concerning the relative importance of several proposed intermediaries in the early phase of endotoxin shock. Experiments were designed to utilize some of the approaches mentioned above.