Effects of nebulized heparin in a rat-model of endotoxemia-induced lung injury

BACKGROUND. Sepsis is a mayor cause of acute lung injury (ALI) and pulmonary coagulopathy is intrinsic to ALI. In sepsis, anticoagulant system is impaired, due to consumption and downregulation by inflammatory mediators. Several studies, in ALI patients and in ALI experimental models, inconsistently suggest beneficial effects of systemic anticoagulants which affect systemic coagulation. Nebulization of anticoagulants might allow for higher pulmonary concentration and reduce the risk of systemic bleeding. METHODS. Adult male Sprague-Dawley rats (250-300 g; n=6/group) were anesthetized with isofluorane and subjected to intratracheal administration (IA) of LPS (10 μg/g b.w.) and IA of saline in control animals. Saline or heparin (1000 IU/kg) were nebulized at 4 and 8h after LPS instillation. Animals were sacrificed 24h after the injury. Inflammatory cells and total proteins were assessed in bronchoalveaolar lavage fluid (BALF). Data are reported as mean±SD. One-way ANOVA was used for multigroup comparisons. RESULTS. Total neutrophil counts were significantly higher in rats instilled with LPS (18.1±6.1x10 7 cells/ml, p 7 cells/ml). Nebulized heparin significantly reduced neutrophils in animals instilled with LPS (12.4±4.3x10 7 cells/ml, p Grant acknowledgment: FIS-PI12/02548, CIBERES and Fundacio Parc Tauli.