This project will explore the nature and etiology of basic physiologic responses that may protect the distal esophageal mucosa against noxious chemical stimuli. The investigators propose to determine the effects of noxious chemical stimuli (capsaicin or acid) applied to the distal esophageal mucosa. Capsaicin is considered to selectively activate primary sensory neurons while acid is a common endogenous noxious chemical stimulus. The effects of stimulation on distal esophageal motility, lower esophageal sphincter activity, mucus secretion and local esophageal blood flow will be monitored. Systemic effects on the cardiovascular, respiratory and gastrointestinal systems will also be determined. Selective procedures will be used to determine the neurophysiologic pathways involved in these responses. All tests will be performed on anesthetized adult dogs. Reflex activity vill be studied following the topical application of capsaicin (2 ml, 0.5%) or acid (5 ml, O.lN-lN HCL) onto the distal esophageal mucosa. Studies will be repeated after denervation procedures or administration of antagonists. Nerve stimulation will be done to delineate neural pathways of conduction. Immunohistochemical studies and radio- immunoassays of tachykinin content in gastroesophageal junctional tissues and in regional blood will also be performed to determine the anatomic distribution and release of Substance P, neurokinin A or neurokinin B. The action of the tachykinins on smooth muscle, blood flow and mucous secretion in this region will be examined. The role that tachykinins might play as nociceptive neurotransmitters in the distal esophagus will be assessed. Chronic acid reflux preparations will be used to study the effects of chronic exposure of the esophageal mucosa to acid on tachykinin content of the distal esophagus. Determining the biological reflexes produced by a nociceptive chemical stimulus in the distal esophagus may have important implications in understanding the entities of non-cardiac chest pain and gastroesophageal reflux.
| Sandler, A D; Schmidt, C; Richardson, K et al. (1993) Regulation of distal esophageal mucosal blood flow: the roles of nitric oxide and substance P. Surgery 114:285-93;discussion 293-4 |
| Sandler, A D; Schlegel, J F; DeSautel, M G et al. (1993) Neuroregulation of a chemosensitive afferent system in the canine distal esophagus. J Surg Res 55:364-71 |
| Sandler, A D; Maher, J W; Weinstock, J V et al. (1993) Functional and morphological characteristics of neuronal substance P in the canine gastroesophageal junction. J Surg Res 55:372-81 |
