Rapid ascent to high altitude may be associated with the development of high-altitude pulmonary edema (HAPE) in susceptible individuals. Because lung lavage fluid obtained from such patients can be rich in protein and neutrophils, we considered that an element of lung injury and inflammation contributed to the pathogenesis of some forms of HAPE. On the basis of such a likely contribution of inflammatory mechanisms, we induced pulmonary lung injury and inflammation by priming rats with Salmonella enteritidis endotoxin (ETX) (0.1 or 0.5 mg/kg body wt ip) and examined the influence of added exposure to simulated hypobaric hypoxia (24 h, 4,300 m). The animals that were primed with ETX and exposed to hypoxia, but not those that received either ETX or hypoxia alone, developed lung vascular damage. This vascular damage manifested itself histologically and by increases in the lung vascular permeability-surface area product and the lung bloodless wet weight-to-dry weight ratio. The bronchoalveolar lavage fluid of ETX-primed hypoxia-exposed rats contained a greater number of white blood cells and a higher concentration of protein compared with that of the ETX-primed rats. Hearts of ETX + hypoxia-treated rats showed an increased ratio of right ventricular weight divided by body weight (RV/BW). Neutropenia prevented the development of pulmonary edema and the increase in ETX + hypoxia rats with a Ca2+ entry blocker inhibited lung injury and RV hypertrophy, these results indicate that ETX priming causes pulmonary edema at high altitude and suggest a role for neutrophils and Ca2+ in this rat model of lung injury.
- Copyright © 1993 the American Physiological Society