Neurogenic pulmonary edema (NPE) is a form of edema that may develop after CNA trauma that intensely activates the sympathetic nervous system. Although NPE has generally been considered to be a hemodynamic form of edema caused by the translocation of a volume overload of blood from the systemic to the pulmonary circuit, important questions remain regarding the role that vascular barotraums (which may, in turn, result in increased protein permeability) and pulmonary vasoconstriction may play in the development of NPE. The purpose of this study will be to test the possibility that these mechanisms may be involved in the development of this disorder. The studies that will be conducted in this invesigation are aimed at the long-term objective of understanding the pathogenesis of this disorder. In Part One of this study, it will be detemrined if vascular damage occurs at pulmonary vascular pressures known to develop in patients with NPE. This will be done by mechanically raising vascular pressure to various levels in a canine isolated perfused lung lobe preparation and determining if the permeability (as evaluated by the hematocrit-protein double-indicator technique) to both total proteins and selected individual proteins (albumin, IgG, and IgM) is increased under these conditions and if it remains so after pressure is returned to control levels. In Part Two of the study, it will be determined if pumonary edema may continue to develop (due to increased permeability) after normal vascular pressures are reattained in a canine model of NPE, by making serial measurements of lung extravascular thermal water (thermal-dye double indicator technique). In these experiments, NPE will be produced by the intracisternal injection of veratrine. In Part Three of the study, it will be determined if pulmonary vasoconstriction occurs in veratrine-induced NPE, if the increase in vascular tone is mediated by adrenal catecholamines, and if there are changes in the pulmonary vascular resistance distribution (as evaluated by the double-occlusion technique) that may favor the development of edema. This will be done by studying the responses of a canine in situ perfused lung lobe preparation when the adrenals are intact and after adrenalectomy.
