We hypothesize that the nebulization of γ-
tocopherol (g-T) in the airway of our ovine model of
acute respiratory distress syndrome will effectively improve pulmonary function following
burn and
smoke inhalation after 96 h. 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 h after the injury (g-T group, n = 6), whereas the control group (n = 5) was nebulized with only
ethanol. Animals were weaned from the
ventilator when possible. All animals were killed after 96 h, with the exception of one untreated animal that was killed after 64 h. Lung g-T concentration significantly increased after g-T nebulization compared with the control group (38.5 ± 16.8 vs. 0.39 ± 0.46 nmol/g, P < 0.01). The PaO(2)/FIO(2) ratio was significantly higher
after treatment with g-T compared with 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
acute lung injury patients who have sustained oxidative damage to the airway.