All analysis of the mechanisms involved in the pathogenesis of the visceral lesions produced by Shiga toxin in the dog has indicated that the structural changes are produced by a vascular mechanism which is under control of the sympathetic nervous system. Paralysis of the latter at the myoneural junction or in the ganglia by means of drugs served to prevent the tissue changes as well as the hyperglycemia and hemoconcentration characteristic of the sympathomimetic response. The observations indicated that the toxin acted via a mechanism located in the central nervous system.
Further studies of the action of Shiga toxin by means of cerebral cross-circulation are reported here. In these the cerebral blood flow of one dog derived from the circulation of the trunk and limbs of another. Injection of the toxin into the femoral vein of this latter dog resulted in the appearance of visceral lesions, hemoconcentration, and hyperglycemia in the former whose brain only received blood containing the toxin. The resulting visceral changes were identical with those observed in the intact unanesthetized dog which had received the toxin directly. The observations indicate that, in dogs, Shiga toxin produces its characteristic visceral lesions via the central nervous system. Possible mechanisms are discussed.