Smoke-induced Acute Lung Injury Research Articles

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

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. Randomized, controlled study. Research laboratory. Anesthetized, paralyzed, and artificially ventilated rats (n = 100) were used. 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 1 (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. 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-alpha and interleukin-1beta 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. 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.

Cyclooxygenase and lipoxygenase inhibition by BW-755C reduces acrolein smoke-induced acute lung injury.

Inhalation of smoke containing acrolein, the most common toxin in urban fires after carbon monoxide, causes vascular injury with non-cardiogenic pulmonary edema containing potentially edematogenic eicosanoids such as thromboxane (Tx) B2, leukotriene (LT) B4, and the sulfidopeptide LTs (LTC4, LTD4, and LTE4). To determine which eicosanoids are important in the acute lung injury, we pretreated sheep with BW-755C (a combined cyclooxygenase and lipoxygenase inhibitor), U-63557A (a specific Tx synthetase inhibitor), or indomethacin (a cyclooxygenase inhibitor) before a 10-min exposure to a synthetic smoke containing carbon particles (4 microns) with acrolein and compared the results with those from control sheep that received only carbon smoke. Acrolein smoke induced a fall in arterial PO2 and rises in peak inspiratory pressure, main pulmonary arterial pressure, pulmonary vascular resistance, lung lymph flow, and the blood-free wet-to-dry weight ratio. BW-755C delayed the rise in peak inspiratory pressure and prevented the fall in arterial PO2, the rise in lymph flow, and the rise in wet-to-dry weight ratio. Neither indomethacin nor U-63557A prevented the increase in lymph flow or wet-to-dry weight ratio, although they did blunt and delay the rise in airway pressure and did prevent the rises in pulmonary arterial pressure and pulmonary vascular resistance. Thus, cyclooxygenase products, probably Tx, are responsible for the pulmonary hypertension after acrolein smoke and to some extent for the increased airway resistance but not the pulmonary edema. Prevention of high-permeability pulmonary edema after smoke with BW-755C suggests that LTB4, may be etiologic, as previous work has eliminated LTC4, LTD4, and LTE4.