Whole-body moderate hypothermia confers protection from wood smoke-induced acute lung injury in rats: The therapeutic window

objective: Toxic smoke inhalation causes acute lung injury. We studied the efficacy and therapeutic window of whole-body hypothermia in rats with wood smoke-induced acute lung injury. Design: Randomized, controlled study. Setting. Research laboratory. Subjects: Anesthetized, paralyzed, and artificially ventilated rats (n = 100) were used. Interventions. Air or wood smoke (30 breaths) was delivered into the lung using a respirator. Immediately after challenge, the rat's colonic temperature was kept a) 37 degrees C (normothermia, NT) for I (NT-1-Air and NT-1-Smoke), 2.5 (NT-2.5-Air and NT-2.5-Smoke), or 5 hrs (NT-5-Air and NT-5-Smoke) in six groups; b) 30 degrees C (hypothermia, HT) for 2.5 (HT-2.5-Smoke) or 5 hrs (HT-5-Air and HT-5-Smoke) in three groups; c) 30 degrees C for the first 2.5 hrs followed by 37 degrees C for another 2.5 hrs (HT-NT-5-Smoke) in one group; or d) 37 degrees C for the first 2.5 hrs followed by 30 degrees C for another 2.5 hrs (NT-HT-5-Smoke) in on group. Measurements and Main Results. Various acute lung injury indexes were assessed at 1, 2.5, or 5 hrs after challenge. In the air group, whole-body hypothermia did not affect the level of lung lipid peroxidation and the amount of proteins, total and differential cell counts, and concentrations of tumor necrosis factor-et and interleukin-1 beta in bronchoalveolar lavage fluid. In the smoke groups, these acute lung injury indexes were increased showing that NT-5-Smoke > NT-2.5-Smoke > NT-1-Smoke. Whole-body hypothermia prevented increases in these acute lung injury indexes in the HT-2.5-Smoke and HT-5-Smoke groups. The efficacy of whole-body hypothermia in the HT-NT-5-Smoke group was superior to that in the NT-HT-5-Smoke group and similar to that in the HT-5-Smoke group. Whole-body hypothermia also alleviated smoke-induced poor gas exchange, pulmonary edema, and pathohistologic injurious signs. Conclusions: Whole-body hypothermia confers protection from wood smoke-induced acute lung injury in rats by suppressing oxidant bronchoalveolar damage and pulmonary inflammation. Early and short-period (2 hrs) application of whole-body hypothermia provides favorable therapeutic effects.