A COMPARISON AMONG ANIMAL-MODELS OF ACUTE LUNG INJURY

Objectives: To compare four widely used animal models of acute lung in jury and to determine the changes in physiologic variables associated with each model.Design: A prospective, controlled animal study. Settin g: An animal laboratory of a university-affiliated children's hospital . Subjects: Four groups of anesthetized, paralyzed, and ventilated you ng Yorkshire pigs, weighing 35 to 45 kg. Interventions: Acute lung inj ury was generated by four different methods: a) intrapulmonary arteria l infusion of endotoxin of Escherichia coli; b) bronchoalveolar instil lation of 0.05N of hydrochloric acid; c) repeated bronchoalveolar warm saline lavage; and d) intrapulmonary arterial infusion of oleic acid. After each acute lung injury procedure, the temporal changes in vario us physiologic variables were measured, starting at 60 mins and at 15- min intervals thereafter for a total of 165 mins. Systemic and mixed v enous serum immunoreactive tumor necrosis factor (TNF)-alpha concentra tions were also measured at the same time points. Analysis of variance for repeated measures was employed to determine the absolute and rela tive significance of the changes observed. Measurements and Main Resul ts: Systemic and mixed venous immunoreactive TNF-alpha did not change following any of the acute lung injury procedures. The animals' heart rates and systemic vascular resistances also did not change. Hydrochlo ric acid instillation as well as bronchoalveolar lavage resulted in si gnificant hypoxemia with no other hemodynamic effects. Endotoxin infus ion did not result in hypoxemia but caused significant increases in me an pulmonary arterial pressure and pulmonary vascular resistance and d ecreases in mean arterial pressure and cardiac output. Oleic acid infu sion resulted in a marked hypoxemia with a pronounced increase in mean pulmonary arterial pressure and pulmonary vascular resistance. It als o markedly reduced the mean arterial pressure, cardiac output, and the mixed venous Po-2. Conclusions: The surfactant depletion and hydrochl oric acid instillation models produce acute hypoxemia in an otherwise hemodynamically stable animal. A brief endotoxin infusion provides a m odel for cardiovascular instability and pulmonary hypertension but fai ls to produce hypoxemia in the pig. The oleic acid infusion creates a model of marked cardiovascular instability, pulmonary hypertension, an d profound hypoxemia. However, none of the acute lung injury models de scribed was associated with the production of tumor necrosis factor.