The mechanism for the high incidence of gastroesophageal reflux (GER) reported in a wide variety of chronic respiratory disorders in children is unknown. To examine the mechanisms of GER in pulmonary disease, we have utilized and validated an anesthetized animal model in cats which permits simultaneous measurements of cardiopulmonary and esophageal function. Initial studies suggest that two separate components of the respiratory system may be factors in the control of the anti-reflux barrier at the gastroesophageal (GE) junction: 1) contraction of the crural diaphragm during inspiration may augment the strength of the intrinsic lower esophageal sphincter (LES), and 2) stimulation of lung and airway receptors may induce transient relaxation of the LES.
The specific aims are to use established methods in cats to evaluate diaphragmatic contraction and stimulate pulmonary afferent receptors to study the affects of these two respiratory components on the gastroesophageal junction. In the diaphragm studies, we first will determine the isolated contributions of costal and crural diaphragm to the intraluminal pressure measured within the LES and the strength of the anti-reflux barrier. Force output of diaphragmatic contraction will be measured by transdiaphragmatic pressure, intraluminal pressure by esophageal manomnetry, and the strength of the anti-reflux barrier by a validated test of gastrointestinal sphincter resistance. Similar techniques will be used to determine the relative magnitude of the contributions of the intrinsic LES and the combined diaphragms to the anti-reflux barrier during spontaneous respiration. In receptor studies, in phrenicotomized animals, the change in LES pressure measured by intraluminal manometry will be determined following stimulation of pulmonary stretch receptors by lung inflation, and pulmonary C-fibers by intra-atrial phenyldiguanide. The effect of selected pulmonary vagal denervation on the observed responses will be studied during hyperinflation induced by continuous positive pressure breathing, and of receptor evoked responses during histamine induced bronchoconstriction. These studies will evaluate, therefore, the role of new mechanisms that we are proposing to explain the known association between GER and pulmonary disease. Results of these studies will not only lead to an understanding of the pathophysiological mechanisms involved, but also to improved therapeutic approaches to this problem in children with chronic respiratory disease.
