Lung function, permeability, and surfactant composition in oleic acid-induced acute lung injury in rats

Abstract

Although acute lung injury (ALI) is associated with inflammation and surfactant dysfunction, the precise sequence of these changes remains poorly described. We used oleic acid to study the pathogenesis of ALI in spontaneously breathing anesthetized rats. We found that lung pathology can occur far more rapidly than previously appreciated. Lung neutrophils were increased approximately threefold within 5 min, and surfactant composition was dramatically altered within 15 min. Alveolar cholesterol increased by approximately 200%, and even though disaturated phospholipids increased by approximately 30% over 4 h, the disaturated phospholipid-to-total phospholipid ratio fell. Although the alveolocapillary barrier was profoundly disrupted after just 15 min, with marked elevations in lung fluid ((99m)Tc-labeled diethylenetriamine pentaacetic acid) and (125)I-labeled albumin flux, the lung rapidly began to regain its sieving properties. Despite the restoration in lung permeability, the animals remained hypoxic even though minute ventilation was increased approximately twofold and static compliance progressively deteriorated. This study highlights that ALI can set in motion a sequence of events continuing the respiratory failure irrespective of the alveolar surfactant pool size and the status of the alveolocapillary barrier.

Analysis of Bronchoalveolar Lavage Fluid Adhering to Lung Surfactant

“…Schmidt et al pointed out changes in the ratio of saturated fatty acid and unsaturated fatty acid in the BALF of 39 patients with acute respiratory distress syndrome (ARDS) and reported a decrease in the patients' lung surface tension with administration of phosphatidylcholine, the main component of saturated fatty acid 22) . In addition, Davidson et al pointed out reduced lung compliance in rats with acute lung obstructions and reported a difference in unsaturated fatty acid concentration 23) . We could not find any experiments like ours that assessed surfactant function by BALF surface tension.…”

Neither fibrin nor plasminogen activator inhibitor-1 deficiency protects lung function in a mouse model of acute lung injury

“…However, it is also important to note that more recent evidence suggests that plasma proteins may have less effect on the surface tension lowering capacity of surfactant (35,41) than originally believed. In fact cholesterols, elevated to the levels measured in the airways of subjects with ALI (14,44), more prominently inhibit the surface tension lowering effects of surfactant in vitro than do serum proteins (21), a disparity that could also apply in vivo. With this in mind, it is curious to note that most studies reporting improved lung function with the use of fibrinolytic agents in ALI have focused predominantly on ventilationperfusion matching and oxygenation (2,16,50,57), with limited reporting on changes in lung mechanical function.…”

Regulatory effects of hydrogen sulfide on alveolar epithelial cell endoplasmic reticulum stress in rats with acute lung injury

“…At the termination of the experiment, rats were anesthetized by intraperitoneal injection with 0.25% pentobarbital sodium at 40 mg/kg at each time point. [18] …”