TRAUMA-INDUCED COAGULOPATHY IS ASSOCIATED WITH A COMPLEX INFLAMMATORY RESPONSE IN THE RAT

Severe trauma can lead to a coagulopathy in patients, which is associated with increased mortality. We developed a rat polytrauma model that demonstrates a similar progression of coagulopathy. Because coagulation is influenced by changes in inflammation, and this interrelationship is poorly understood, we have studied the progression of inflammation, and its correlation with coagulation, in this rat model of severe polytrauma. Sprague-Dawley rats were anesthetized with isoflurane. Polytrauma was induced by damaging 10 cm of small intestines, right and medial liver lobes, right leg skeletal muscle, femur fracture, and hemorrhaging 40% of blood volume. No resuscitation was given. Polytrauma and hemorrhage resulted in a significant decrease in the number of lymphocytes and an increase in monocytes and granulocytes. There was an increase in plasma proinflammatory cytokines: tumor necrosis factor alpha(40x), interleukin (IL)-6 (20x), IL-1 beta (16x), IL-17 (15x), interferon gamma (10x), IL-1 alpha (8x) and IL-12p70 (5x); anti-inflammatory cytokines: IL-10 (100x), IL-13 (16x), and IL-4 (5x); chemokines: growth-regulated protein/keratinocyte chemoattractant (30x), macrophage inflammatory protein 3 alpha (10x), regulated and normal T-cell expressed and secreted (3x); and growth factors: vascular endothelial growth factor (5x), granulocyte macrophage colony-stimulating factor (6x), macrophage colony-stimulating factor (3x), granulocyte colony-stimulating factor (2x), and IL-5 (3x). There was a strong and significant correlation between prothrombin time, activated partial thromboplastin time, fibrinogen, and fibrin monomer concentration, and many cytokines. Polytrauma with hemorrhage is associated with a coagulopathy and a complex inflammatory response consisting of a concurrent rise in both proinflammatory and anti-inflammatory cytokines. The rise in plasma concentrations of chemokines and growth factors likely contribute to the mobilization of monocytes and granulocytes. There is strong correlation between prothrombin time, activated partial thromboplastin time, and IL-10 and IL-1". This relationship could be exploited for the development of resuscitation strategies that attenuate these cytokines and allow for better outcomes in patients with trauma through concomitant modulation of inflammation and coagulopathy.