Pathogenesis of Dysentery Intoxication

In the course of studying the mechanism whereby Shiga toxin produces, visceral lesions, it became increasingly clear that the toxin produced its effects indirectly. Direct contact between the toxin and intestinal mucosa in dogs produced no lesions in the exposed loop (1). Certain anatomical peculiarities of the lesions pointed to a vascular component in the development of the structural changes. I t was found that the widely distributed alterations usually associated with the morphological picture of Shiga enteritis occurred in a late, and often terminal, stage of the intoxication. Serial studies timed to investigate the early stages of the lesions revealed that the initial changes were focal in nature, and that the later alterations were the result of the confluence of numerous focal lesions (1). There were no visible alterations in the structure of the vessel walls, but the tissue edema and extravasation of blood cells left no doubt as to changes in permeability of the vascular bed. These "functional" alterations were attributed to the occurrence of vasospasm in the involved areas (2). Subsequent studies were devoted to an analysis of the mechanism of the production of the vasospasm. We were able to show that this occurred in close temporal relationship to the appearance of hemoconcentration and hyperglycemia. As a result, we hypothesized that the vasospasm resulted from a homeostatic reaction on the part of the organism. This diffuse, systemic sympathomimetic reaction produced the hyperglycemia on the one hand and on the other caused the vasospasm. The hemoconcentration which was uniformly found was interpreted as the result of the increased permeability of the capillaries which simultaneously produced the edematous and ulcerative lesions in the alimentary tract. In further studies it was found that by pretreating our animals with ergotamine tartrate we were able to inhibit the hyperglycemia, hemoconcentration, and occurrence of the anatomical lesions (3). This indicated that the point of primary action of the toxin was somewhere proximal to the final common