title: Differential effects of fresh frozen plasma and normal saline on secondary brain damage in a large animal model of polytrauma, hemorrhage and traumatic brain injury.
abstract: BACKGROUND
  We have previously shown that the extent of traumatic brain injury (TBI) in large animal models can be reduced with early infusion of fresh frozen plasma (FFP), but the precise mechanisms remain unclear. In this study, we investigated whether resuscitation with FFP or normal saline differed in their effects on cerebral metabolism and excitotoxic secondary brain injury in a model of polytrauma, TBI, and hemorrhagic shock.
  
  
  METHODS
  Yorkshire swine (n = 10) underwent Grade III liver injury, rib fracture, standardized TBI, and volume-controlled hemorrhage, (40% ± 5%) and were randomly resuscitated with either FFP or normal saline. Hemodynamic parameters and brain oxygenation were continuously monitored, while microdialysis was used to measure the brain concentrations of pyruvate, lactate, glutamate, and glycerol at baseline; 1 hour and 2 hours after shock; immediate postresuscitation (PR); as well as 2, 4, and 6 hours PR. Cells from the injured hemisphere were separated into mitochondrial and cytosolic fractions and analyzed for activity of the pyruvate dehydrogenase complex (PDH).
  
  
  RESULTS
  There were no baseline differences in cerebral perfusion pressure, brain oxygenation, as well as concentrations of pyruvate, lactate, glutamate, and glycerol between the groups. At 2 hours and 4 hours PR, the FFP group had significantly higher cerebral perfusion pressures (52 [5] mm Hg vs. 43 [2] mm Hg, p = 0.016; and 50 [7] mm Hg vs. 37 [1] mm Hg, p = 0.008, respectively). There was a sustained and significant (p < 0.05) drop in the glutamate and glycerol levels in the FFP group, implying a decrease in excitotoxicity and brain damage, respectively. Mitochondrial PDH activity was significantly higher (2,666.2 [638.2] adjusted volume INT × mm vs. 1,293.4 [88.8] adjusted volume INT × mm, p = 0.008), and cytosolic PDH activity was correspondingly lower (671.4 [209.2] adjusted volume INT × mm vs. 3070.7 [484.3] adjusted volume INT × mm, p < 0.001) in the FFP group, suggesting an attenuation of mitochondrial dysfunction and permeability.
  
  
  CONCLUSIONS
  In this model of TBI, polytrauma, and hemorrhage, FFP resuscitation confers neuroprotection by improving cerebral perfusion, diminishing glutamate-mediated excitotoxic secondary brain injury and reducing mitochondrial dysfunction.
authors.affiliation: From the Division of Trauma, Emergency Surgery and Surgical Critical Care (J.O.H., A.M.I., G.J., B.L., Y.L., M.S., C.H.J., J.L., M.A.D., H.B.A.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; and the Department of Surgery (G.J., B.L., H.B.A.), University of Michigan Hospital, Ann Arbor, Michigan.
authors.forename: John O
authors.initials: JO
authors.lastname: Hwabejire
authors.forename: Ayesha M
authors.initials: AM
authors.lastname: Imam
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Baoling
authors.initials: B
authors.lastname: Liu
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Li
authors.forename: Martin
authors.initials: M
authors.lastname: Sillesen
authors.forename: Cecilie H
authors.initials: CH
authors.lastname: Jepsen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lu
authors.forename: Marc A
authors.initials: MA
authors.lastname: deMoya
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics; D007427:Intracranial Pressure; D007552:Isotonic Solutions / Q000627:therapeutic use*; D009104:Multiple Trauma / Q000150:complications / Q000628:therapy*; D010949:Plasma; D011379:Prognosis; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000097:blood / Q000209:etiology / Q000628:therapy*; D013552:Swine
chemical_list: D007552:Isotonic Solutions