(RSS) Karim's Weblog
Random snippets and thoughts - hopefully mostly trauma related!
Authors
- Karim Brohi
- trauma.org; London
(RSS) Trauma Research Blog
Selected new & juicy research papers, with editorial comment.
Authors
- Karim Brohi
- trauma.org; London
Recent Posts:
So, just in time for this year's London Trauma Conference, we've uploaded the presentations from the 'Trauma Massive Transfusion & Coagulopathy State of the Art Symposium' held at the London Trauma Conference in 2008. This set of lectures presents an overview of the current state of knowledge in the exploding field of Trauma Induced Coagulopathy (TIC) and transfusion practice. At this year's conference we'll be holding a complementary Scientific Symposium on Trauma Haemostasis & Transfusion. The programme is just being finalized and will be available in the next few days. Meanwhile, enjoy the presentations from last year - and TRAUMA.ORG's new video channel on Vimeo.
PubMed ID: 19628092
Surgery. 2009 Aug;146(2):325-33.
Authors: Alam HB, Shuja F, Butt MU, Duggan M, Li Y, Zacharias N, Fukudome EY, Liu B, Demoya M, Velmahos GC.
Abstract:
BACKGROUND: We have demonstrated previously that valproic acid (VPA), a histone deacetylase inhibitor, can improve survival in lethal models of hemorrhagic shock. This study investigated whether VPA treatment would improve survival in a clinically relevant large animal model of poly-trauma/hemorrhagic shock, and whether the protective effects are executed through the Akt survival pathway. METHODS: Yorkshire swine were subjected to a poly-trauma protocol including: (1) Pre-hospital phase- Femur fracture, 60% hemorrhage, 30 min of shock (mean arterial pressure [MAP]: 25-30 mmHg), and infusion of 154mM NaCl (3 x shed blood); (2) Early hospital phase A Grade V liver injury (simulating rupture of a previously contained hematoma) followed by liver packing; (3) Treatment/monitoring phase randomization to 3 treatment groups (n = 6-8/group): no treatment (control), fresh whole blood (FWB), and intravenous VPA (400 mg/kg, given during the pre-hospital phase). Animals were monitored for 4 h, with survival being the primary endpoint. Liver tissue was subjected to Western blot analysis. RESULTS: FWB (n = 6) and VPA treatments (n = 7) significantly increased survival (100% and 86%, respectively) compared to control group (n = 8) (25%). The protocol produced significant anemia (Hb<6 g/dL) and lactic acidosis (lactate 3-5 mmol/L). Acidosis improved after blood transfusion and worsened in the other two groups. VPA treatment increased phospho-Akt (activated), phospho-GSK-3beta (Glycogen synthase kinase 3beta), beta-catenin and Bcl-2 (B-cell leukemia/lymphoma 2) protein levels compared to control group (P = .01, .01, .03, and .02, respectively). There was no significant difference in the level of these proteins between the control and FWB groups. CONCLUSION: Treatment with VPA without blood transfusion improves early survival in a highly lethal poly-trauma and hemorrhagic shock model. The survival advantage is due not to improvement in resuscitation but to better tolerance of shock by the cells, in part due to the preservation of the Akt survival pathway.Notes & Commentary:
Sodium valproate protects cells from ischaemic damage in this haemorrhagic shock model. There are a number of potential therapeutics options for both ischaemia protection and ischaemia rescue ready for translational trials now.
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