Douglas Z Liou1, Ara Ko1, Oksana Volod2, Galinos Barmparas1, Megan Y Harada1, Matthew J Martin3, Ali Salim4, Navpreet Dhillon1, Gretchen M Thomsen5, Eric J Ley6. 1. Department of Surgery, Division of Trauma and Critical Care, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Suite 8215N, Los Angeles, CA, 90048, USA. 2. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 3. Department of Surgery, Madigan Army Medical Center, Tacoma, WA, USA. 4. Department of Surgery, Division of Trauma, Burn, and Surgical Critical Care, Brigham and Women's Hospital, Boston, MA, USA. 5. Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 6. Department of Surgery, Division of Trauma and Critical Care, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Suite 8215N, Los Angeles, CA, 90048, USA. Eric.Ley@cshs.org.
Abstract
BACKGROUND: The source of coagulopathy in traumatic brain injury (TBI) is multifactorial and may include adrenergic stimulation. The aim of this study was to assess coagulopathy after TBI using thromboelastography (TEG), and to investigate the implications of β-adrenergic receptor knockout. METHODS: Adult male wild type c57/bl6 (WT) and β1/β2-adrenergic receptor knockout (BKO) mice were assigned to either TBI (WT-TBI, BKO-TBI) or sham injury (WT-sham, BKO-sham). Mice assigned to TBI were subject to controlled cortical impact (CCI). At 24 h post-injury, whole blood samples were obtained and taken immediately for TEG. RESULTS: At 24 h after injury, a trend toward increased fibrinolysis was seen in WT-TBI compared to WT-sham although this did not reach significance (EPL 8.1 vs. 0 %, p = 0.18). No differences were noted in fibrinolysis in BKO-TBI compared to BKO-sham (LY30 2.6 vs. 2.5 %, p = 0.61; EPL 3.4 vs. 2.9 %, p = 0.61). In addition BKO-TBI demonstrated increased clot strength compared to BKO-sham (MA 76.6 vs. 68.6, p = 0.03; G 18.2 vs. 11.3, p = 0.03). CONCLUSIONS: In a mouse TBI model, WT mice sustaining TBI demonstrated a trend toward increased fibrinolysis at 24 h after injury while BKO mice did not. These findings suggest β-blockade may attenuate the coagulopathy of TBI and minimize progression of intracranial hemorrhage by reducing fibrinolysis and increasing clot strength.
BACKGROUND: The source of coagulopathy in traumatic brain injury (TBI) is multifactorial and may include adrenergic stimulation. The aim of this study was to assess coagulopathy after TBI using thromboelastography (TEG), and to investigate the implications of β-adrenergic receptor knockout. METHODS: Adult male wild type c57/bl6 (WT) and β1/β2-adrenergic receptor knockout (BKO) mice were assigned to either TBI (WT-TBI, BKO-TBI) or sham injury (WT-sham, BKO-sham). Mice assigned to TBI were subject to controlled cortical impact (CCI). At 24 h post-injury, whole blood samples were obtained and taken immediately for TEG. RESULTS: At 24 h after injury, a trend toward increased fibrinolysis was seen in WT-TBI compared to WT-sham although this did not reach significance (EPL 8.1 vs. 0 %, p = 0.18). No differences were noted in fibrinolysis in BKO-TBI compared to BKO-sham (LY30 2.6 vs. 2.5 %, p = 0.61; EPL 3.4 vs. 2.9 %, p = 0.61). In addition BKO-TBI demonstrated increased clot strength compared to BKO-sham (MA 76.6 vs. 68.6, p = 0.03; G 18.2 vs. 11.3, p = 0.03). CONCLUSIONS: In a mouse TBI model, WT mice sustaining TBI demonstrated a trend toward increased fibrinolysis at 24 h after injury while BKOmice did not. These findings suggest β-blockade may attenuate the coagulopathy of TBI and minimize progression of intracranial hemorrhage by reducing fibrinolysis and increasing clot strength.
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