Neurogenic Pulmonary Edema Induced by Anterior Hypothalamic Lesions in Rats

Abstract

Head trauma and brain damage have long been associated with the occurrence of acute pulmonary edema. This study explores the possibility that neurogenic pulmonary edema (NPE) is hypothalamic in Qrigin and due to a deficit of control. Rats received bilateral electrolytic lesions in the anterior hypothalamic region of the brain. The lesions were varied intentionally in both size and specific location. The occurrence of behavioral changes associated with pulmonary edema were nQted. The rats were subject to gross autopsy and the appearance of the lungs and lung weights were recorded. The brains were removed, fixed in buffered formalin and frozen serial sections (40 or 80 u thick) were studied. The brain section with the most bilateral cystic damage (by visual inspection) was regarded as the lesion midpoint. The anterior-posterior (A-P) lesion midpoint location and extent of overlapping A-P bilateral brain damage due to the lesions were recorded. With good quality 40 u sections, it was possible to estimate the (A-P) lesion locations to the nearest 0.1 mm. With preparations of poorer quality the lesion coordinates were determined to the nearest 0.2 mm. Of 26 rats, five were found to have developed NPE within 3 hours of lesioning (NPE is defined as having a lung wet weight/body weight ratio over two standard deviations above the mean of the ratios for rats without NPE.) Unlike some earlier reports, a consistent relationship was noted between the size and placement of the brain lesions and the incidence of NPE. Edema-generating brain lesions were found to be a minimum of 1.2 mm long (A-P). In 5 rats with NPE, the bilateral lesion midpoint was within the anterior hypothalamus in the region 8.0-8.4 mm rostral of the interaural line (a region rostral to the optic chiasm). Rats with lesion midpoints between 8.0-8.4 mm and not demonstrating NPE were found to have lesions less than the critical minimum·length of 1.2 mm. Our results clarify some of the paradoxical observations made by previous investigators and suggest that a discrete anterior hypothalamic region is normally responsible for preventing pulmonary vascular hypertension in rats.