The purpose of the proposed studies is to examine the pathophysiological mechanisms involved in the development of neurogenic pulmonary edema. We will examine the effects of activation of sympathetic nervous system on pulmonary transvascular fluid and protein exchange in sheep and dogs to assess the basis for increase in the transvascular fluid and protein fluxes, and the apparent species differences. The role of the Alpha- and Beta-adrenoceptors in mediating the increases in transvascular fluid and protein fluxes will also be examined. In other studies, we will assess the hypothesis that marked transient increases in pulmonary microvascular pressure induce increase in lung vascular permeability. We will determine the duration and degree of pressure rise required to increase lung vascular permeability. We will test the hypothesis that transient pulmonary capillary hypertension associated with increased sympathetic stimulation can result in fulminant neurogenic pulmonary edema. We will describe the ultrastructural morphological alterations occurring following the pressure-induced development of pulmonary edema. In other studies, we will examine the modulatory influence of Beta-adrenergic receptors in regulating pulmonary vascular permeability in both the normal lung and after increased lung vascular permeability. We will characterize the generation of arachidonic acid end-products following the sympathetic nerve stimulation and their role in mediating the alterations in lung fluid balance. The final series of studies will examine the development of neurogenic pulmonary edema in cats with respect to the hemodynamic and morphological alteration occurring during edema formation. The intent of the studies in the proposal is to provide a clearer and in-depth picture of the physical and neurohumoral factors involved in he development of pulmonary edema. With a better description of the pathophysiology of neurogenic pulmonary edema, more appropriate therapies can be directed at only the etiologic factors.
Showing the most recent 10 out of 102 publications
