Aerosolized Heparin Mitigates Chlorine-Induced Lung Injury

Chlorine (Cl 2 ) is a toxic oxidative gas that can cause acute lung injury (ALI) and death when inhaled at high concentrations for extended periods of time. Used in the production of pharmaceuticals, Cl 2 exposure can occur in industrial or transportation accidents, which are common enough to pose a serious health risk. Cl 2 insult results in coagulatory dysfunction, inflammatory damage and increased lung permeability. Thus we hypothesized that delivery of aerosolized heparin, which is an anticoagulant that decreases fibrin deposition and does not cause significant systemic bleeding when administered intranasally, may decrease lung injury. C57BL/6 mice were exposed to 400ppm Cl 2 for 30min in environmental chambers and returned to room air . Immediately following Cl 2 exposure , they were connected to a nebulizer and breathed heparin or vehicle for 20 min. At 1hr post aerosol, blood and bronchoalveolar lavage fluid (BALF) were taken for native rotational thromboelastometry (NATEM) and thrombin antithrombin (TAT) formation measurements (an index of clotting). At 6hrs post aerosol, BALF from a second group of mice was taken for measurements of total protein (an index of increased blood‐gas permeability) and white blood cell (WBC) numbers (an index of inflammation). Mice that received heparin had significantly faster coagulatory times and significantly lower levels of total protein and number of inflammatory cells in the BALF. These results suggest that heparin mitigates Cl 2 induced lung damage, especially in the reduction of lung permeability, WBC inflammatory responses and post injury hypocoagulation. Grant Funding Source : Supported by: NIEHS grants 5U54ES017218, 5U01ES015676 and a European Respiratory Society Fellowship