Neurogenic pulmonary edema (NPE) is a form of edema that may develop after CNS trauma that massively activates the sympathetic nervous system (SNS). The long term objectives of this program are to determine (1) the basic mechanisms by which such excessive SNS activity affects lung blood flow and fluid balance and how these mechanisms act in concert to produce NPE, and (2) the mechanisms involved in the resolution of this form of edema. An understanding of both the mechanisms of development and recovery is important for the design of effective preventive and treatment measures. We have recently found that the rate of alveolar fluid reabsorption (AFR) is increased during recovery from NPE in a canine model of NPE in which the SNS is massively activated by the administration of veratrine. This project is designed to determine the mechanisms of the increased AFR and has 3 specific aims. The 1st aim is to determine if the increased AFR is mediated by beta-adrenergic stimulated alveolar epithelial sodium reabsorption, and if so, the role played by endogenous epinephrine in this process. Alveolar liquid clearance will be determined from the increase in protein concentration that occurs as fluid is reabsorbed from autologous plasma that has been instilled into the airways. Experiments will be done in adrenalectomized animals and using appropriate blockers to determine the role of adrenal catecholamines, beta2-adrenergic receptors (ICI 118,551), and active Na+ transport (amiloride) in this process.
The second aim i s designed to determine the dose-response relationship between plasma epinephrine concentration and AFR. This will be accomplished by determining AFR after infusing epinephrine concentrations ranging from those observed during mild to massive SNS activation. The 3rd aim is to determine if the increased AFR observed after massive SNS activation is the maximal attainable in the lung. This will be accomplished by determining if the SNS-induced increased in AFR can be further increased by the administration of drugs that increase intracellular cyclic AMP concentration independently (forskolin, theophylline) of beta2-adrenergic receptor activation.
| Maron, M B (1998) Dose-response relationship between plasma epinephrine concentration and alveolar liquid clearance in dogs. J Appl Physiol 85:1702-7 |
| Lane, S M; Maender, K C; Awender, N E et al. (1998) Adrenal epinephrine increases alveolar liquid clearance in a canine model of neurogenic pulmonary edema. Am J Respir Crit Care Med 158:760-8 |
| Grimme, J D; Lane, S M; Maron, M B (1997) Alveolar liquid clearance in multiple nonperfused canine lung lobes. J Appl Physiol 82:348-53 |
