Left ventricular dysfunction (LVD) is a syndrome which presents as dyspnea on exertion, wheezing, a rapid respiratory rate, and increased secretion of mucus. These features are the result of pulmonary venous congestion (PVC) which activates reflexes originating from the airways. Renal functions are also altered. As LVD progresses, PVC evolves into pulmonary edema. This application addresses two issues: (1) the activity of sensory receptors in the lung when the pulmonary circulation is altered chronically by LVD and (2) the reflex effects of activating these receptors on renal function. The majority of these sensory receptors transmit in the cervical vagi and they are classified into myelinated and non-myelinated afferents. The former are composed of pulmonary stretch receptors (PSR) and rapidly adapting receptors (RAR) and the latter of C fiber afferents. Discussions of reflex mechanisms in disease states such as chronic PVC are based on the unsubstantiated assumption that observations made in intact acutely anesthetized animals can be extrapolated directly to animals with chronic disturbances of the circulation. The following hypotheses will be tested in rabbits in a state of chronic pulmonary venous congestion: a) acute pulmonary edema activates pulmonary C fiber afferents, b) acute pulmonary edema increases tone of airway smooth muscle by activation of C fibers and/or RAR, c) acute pulmonary edema increases phrenic nerve activity by activation of C fibers and/or RAR, d) acute pulmonary edema causes a reflex increase in renal blood flow by activation of renal C fiber afferents, and e) the diuresis is associated with obstruction of pulmonary lymph drainage is absent. The following hypotheses will be tested in intact, anesthetized rabbits: a) the diuretic response to pulmonary lymphatic obstruction is not mediated by a change in renal cortico-medullary blood flow and b) the renal response to pulmonary lymphatic obstruction is mediated by nitric oxide related mechanisms.
| Ma, Amy; Bravo, Milo; Kappagoda, C Tissa (2003) Responses of bronchial C-fiber afferents of the rabbit to changes in lung compliance. Respir Physiol Neurobiol 138:155-63 |
