Therapeutic Effects and Anti‐inflammatory Mechanisms of Heparin on Acute Lung Injury in Rabbits

Objectives:  The objectives were to investigate the potential beneficial effects and molecular mechanisms of heparin and low‐molecular‐weight heparin (LMWH) on acute lung injury (ALI). Methods:  Forty‐eight rabbits were randomized into four groups: normal control group (Group A), lipopolysaccharide (LPS) group (Group B), LPS + heparin group (Group C), and LPS + LMWH group (Group D). The rabbit ALI model was established by intravenous (IV) injection with LPS. Alveolar–arterial O 2 difference (P A‐a O 2 ), serum tumor necrosis factor α (TNF‐α), circulating p38 mitogen‐activated protein kinase (p38 MAPK) levels, lung nuclear factor (NF)‐κB levels, and lung dry/wet (D/W) ratio were measured, and the lung injury scores were calculated. Results:  Lipopolysaccharide caused significant increases in P A‐a O 2 , serum TNF‐α, expression of p38 MAPK in polymorphonuclear neutrophils (PMNs), the lung injury scores, and nuclear factor‐κB (NF‐κB) activity in the lung tissue and caused a decrease in lung D/W ratio. A positive linear correlation was found between p38 MAPK and TNF‐α at 1, 2, 4, and 6 hours ( r  = 0.68, 0.92, 0.93, and 0.93, respectively) and between NF‐κB and p38 MAPK and TNF‐α at 6 hours (r = 0.94 and 0.83, respectively). IV heparin or LMWH given after LPS treatment attenuated these changes in inflammatory response, oxygenation, p38 MAPK expression, and NF‐κB activation. Conclusions:  The anti‐inflammatory mechanisms of heparin in ALI may be inhibiting p38 MAPK and NF‐κB activities, and then TNF‐α overexpression, thus alleviating the inflammatory reaction. ACADEMIC EMERGENCY MEDICINE 2008; 15:1–8 © 2008 by the Society for Academic Emergency Medicine