Pathogenesis of acute gastric stress ulcers.

AcuTE ULCEATIONS of the stomach and of the duodenum have been recognized since the nineteenth century when they were described in association with severe body burns 1 and lesions of the brain.2 It has become apparent that the ulcers may follow a variety of stress conditions in man, including multiple injuries and sepsis, but the pathway by which the various disease states lead to acute ulceration remains unsolved. There have been numerous attempts to reproduce these lesions experimentally, including stimulation or ablation of different parts of the brain,' the administration of various pharmacologic agents,7-9 and the employment of restraint stress.10-16 Stimulation of the anterior hypothalamus3'4'17 and destruction of the posterior portion 5'6 have been shown to result in increased gastric acidity and the production of ulcers. Also, restraintinduced ulcers are prevented in part or totally by prior vagotomy 10,14.16 or by the administration of anticholinergic 15'18,19 and sympathomimetic 20 drugs, whereas adrenalectomy 1145 or cholinergic and sympatholytic agents19'20 afford no protection. These observations all tend to indict vagal overactivity as the principal effector in the induction of stress ulcers. In a separate study employing restraint stress, we observed that bacterial products of intestinal origin may play an important role in the central stimulation of the hypothalamus and vagal nuclei and that the prior oral administration of a nonabsorbable antibiotic affords significant protection against the development of the ulcers.19 However, the parts played by the various motor and secretory effects of the vagal action, and the relative importance of vascular changes and the gastric epithelial mucin in the development of the mucosal lesions have not been clarified. A correlative histologic, ultrastructural, and mucin histochemical study of the gastric mucosa in immobilized rats was undertaken, therefore, in an effort to delineate the various factors involved in the pathogenesis of the stress lesion.