Pulmonary complications are the major cause of death in the fire related injuries. The pulmonary injury may be due to smoke inhalation, circulating factors released by burned skin or organs, or the combination of these. The chemical toxins in smoke and not heat are the injurious agents. In this proposal the hypothesis is that smoke induced lung injury is not by the same pathways that produce lung injury in skin burn injury, i.e. complement activation, leukostasis and aggregation, O2 free radical release and arachidonic acid activation. To address this hypothesis, we have developed a synthetic smoke in which only one chemical toxin at a time is added to a charcoal soot instead of the multiple toxins usually present in smoke. The pulmonary injury we have chosen to follow is pulmonary edema which is the usual acute lethal complication of smoke inhalation. Extravascular lung water (EVLW) is monitored serially with a locally developed double-indicator dilution technique which has an r of .93 with wet/dry blood corrected lung weights (n=87) in diffuse lung injury as occurs with smoke inhalation. This technique allows us not only to precisely quantitate the EVLW but determine the time from smoke exposure that edema first develops. We have found that the aldehyde acrolein, the most common toxin in smoke after carbon monoxide, is able to produce a delayed onset pulmonary edema similar to that seen in fire victims. The delay is 40 minutes to 8 hours depending on the dose of acrolein. In this proposal we will seek to determine how acrolein produces pulmonary edema, how acrolein interacts with skin burns to produce lung injury, whether other aldehydes (formaldehyde) also produce pulmonary edema and what role the bronchial artery circulation plays in pulmonary injuries via the airways rather than the blood vessels. These experiments will entail infusion or aerosolization of pharmacologic agents known to inhibit acrolein induced injury in organs other than lung. Infusions of inhibitors of the arachidonic acid cascade and of 02 radicals will also be done to determine the similarity of acrolein lung toxicity to many other lung toxins. We will pursue our studies showing bronchial artery ligation eliminates or diminishes acrolein-smoke induced pulmonary edema and will use monastral blue B to locate which bronchial vessels leak and if bronchial vessels are the only systemic vessels to leak. Finally, we will compare our results on synthetic smoke with real smoke from burning towels (high acrolein) or from burning nylon (low acrolein) to see if acrolein or other aldehydes may be the major edemagenic toxins in smoke.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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Massachusetts General Hospital
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