Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion
| Autor: | Pamela Rahn, Jean-Francois Pittet, Michel Carles, Carolyn S. Calfee, Marybeth Howard, Brian B. Chesebro, Karim Brohi, Mitchell J. Cohen, Sarah C. Christiaans |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Resuscitation Blood Pressure Critical Care and Intensive Care Medicine Tissue plasminogen activator Gastroenterology Medical and Health Sciences Cohort Studies 0302 clinical medicine Penetrating Trauma Centers Heart Rate Craniocerebral Trauma 2.1 Biological and endogenous factors Prospective Studies Survivors HMGB1 Protein Aetiology Lung Acute Respiratory Distress Syndrome 0303 health sciences biology Respiration Blood Proteins Hematology Middle Aged Hyperfibrinolysis 3. Good health Wounds Artificial Female medicine.symptom medicine.drug Adult medicine.medical_specialty Physical Injury - Accidents and Adverse Effects Inflammation Lung injury HMGB1 03 medical and health sciences Rare Diseases Clinical Research Internal medicine medicine Coagulopathy Humans 030304 developmental biology business.industry Inflammatory and immune system 030208 emergency & critical care medicine medicine.disease Emergency & Critical Care Medicine Surgery biology.protein Prothrombin Time Wounds and Injuries business Protein C |
| Zdroj: | Critical care (London, England), vol 13, iss 6 |
| Popis: | IntroductionHigh mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not known and therefore constitutes the aim of the present study.MethodsOne hundred sixty eight patients were studied as part of a prospective cohort study of severe trauma patients admitted to a single Level 1 Trauma center. Blood was drawn within 10 minutes of arrival to the emergency room before the administration of any fluid resuscitation. HMGB1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, von Willebrand Factor (vWF), angiopoietin-2 (Ang-2), Prothrombin time (PT), prothrombin fragments 1+2 (PF1+2), soluble thrombomodulin (sTM), protein C (PC), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and D-Dimers were measured using standard techniques. Base deficit was used as a measure of tissue hypoperfusion. Measurements were compared to outcome measures obtained from the electronic medical record and trauma registry.ResultsPlasma levels of HMGB1 were increased within 30 minutes after severe trauma in humans and correlated with the severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and hyperfibrinolysis as well with a systemic inflammatory response and activation of complement. Non-survivors had significantly higher plasma levels of HMGB1 than survivors. Finally, patients who later developed organ injury, (acute lung injury and acute renal failure) had also significantly higher plasma levels of HMGB1 early after trauma.ConclusionsThe results of this study demonstrate for the first time that HMGB1 is released into the bloodstream early after severe trauma in humans. The release of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|