The quest for an animal model of high altitude pulmonary edema

The understanding of the mechanisms underlying certain human diseases usually requires an animal model which can be manipulated in a way that will allow dissection of the pathophysiologic events which lead to the disease. High altitude pulmonary edema (HAPE) occurs in some healthy individuals who ascend from low to high altitude. The disease is characterized by a high protein leak into the lungs and is associated with accentuated pulmonary hypertension. Attempts to find an animal model for HAPE have been made in a number of animal species, including rats, rabbits, sheep, dogs and ferrets. None has been consistently successful. Utilizing the physiologic characteristic of an accentuated hypoxic pulmonary vascular response, we studied both pigs and rats during the stresses of hypoxia and exercise (rats) and examined the lungs for the cellular, protein, and morphologic changes. Protein and cell contents in the lung lavage of the hypoxic animals were slightly higher than the controls while the presence of von Willebrand factor in the hypoxic animals suggests early epithelial damage. This presentation will review previous attempts to find an animal model of HAPE and will discuss the preliminary results of our studies with their suggestive but not confirmatory results.