Nebulization with Gamma-Tocopherol Ameliorates Acute Lung Injury after Burn and Smoke Inhalation in the Ovine Model

摘要

We hypothesize that the nebulization of gamma-tocopherol (g-T) in the airway of our ovine model of acute respiratory distress syndrome (ARDS) will effectively improve pulmonary function following burn and smoke inhalation after 96 hours. Adult ewes (n=14) were subjected to 40% total body surface area burn and were insufflated with 48 breaths of cotton smoke under deep anesthesia, in a double-blind comparative study. A customized aerosolization device continuously delivered g-T in ethanol with each breath from 3 to 48 hours after the injury (g-T group, n=6), while the control group (n=5) was nebulized with only ethanol. Animals were weaned from the ventilator when possible. All animals were sacrificed after 96 hours, with the exception of one untreated animal that was euthanized after 64 hours. Lung g-T concentration significantly increased after g-T nebulization compared to the control group (38.5±16.8 nmol/g vs. 0.39±0.46, p<0.01). The PaO2/FiO2 ratio was significantly higher after treatment with g-T compared to the control group (310±152 vs 150±27.0, p<0.05). The following clinical parameters were improved with g-T treatment: pulmonary shunt fraction, peak and pause pressures, lung bloodless wet-to-dry weight ratios (2.9±0.87 vs 4.6±1.4, p<0.05), and bronchiolar obstruction (2.0±1.1% vs 4.6±1.7%, p<0.05). Nebulization of g-T, carried by ethanol, improved pulmonary oxygenation and markedly reduced the time necessary for assisted ventilation in burn and smoke injured sheep. Delivery of g-T into the lungs may be a safe, novel, and efficient approach for management of ALI patients who have sustained oxidative damage to the airway.