03.16 Resuscitation of Hemorrhagic Shock Using Fresh Frozen Plasma Prevents Lung ICAM-1 Expression

L. M. Bond1, P. J. Matheson1,2, V. S. Graham1, M. A. Eid1,2, C. N. Kapsalis1,2, A. J. Matheson1,2, C. D. Downard1,2, J. W. Smith1,2  1University Of Louisville,Department Of Surgery,Louisville, KY, USA 2Robley Rex Veterans Affairs Medical Center,Research,Louisville, KY, USA

Introduction:  Hemorrhagic shock (HS) impairs vital organ perfusion to cause tissue hypoxia, compartmental fluid shifts, hypercoagulability, and inflammation. This increases lung neutrophil sequestration, which is partially mediated by altered ICAM-1 expression.  Resuscitation (RES) with blood and i.v. fluids (conventional resuscitation, CR) restores central hemodynamic parameters, but can progress to multiple organ failure and death.  Adding Fresh Frozen Plasma (FFP) to blood RES maintains arterial oxygen delivery to prevent these changes.  We hypothesized that RES using FFP might restore liver blood flow (LBF) and prevent increased ICAM-1 expression to minimize lung neutrophil infiltration.

Methods:  Anesthetized male Sprague-Dawley rats were randomized to groups (n=8/gp): 1) Sham, 2) Sham+FFP, 3) HS/CR, or 4) HS+FFP.  Sham animals underwent surgery, but no HS/CR.  HS was 40% MAP (60 min) and CR was return of shed blood + 2 volumes of i.v. normal saline.  HS+FFP received shed blood plus one volume of pre-warmed FFP.  Liver blood flow was by galactose clearance.  After 4 hours, samples were harvested. Lung pathology was graded by pathologist blinded to groups in H&E and lung ICAM-1 immunohistochemistry (IHC).  

Results: LBF was decreased in HS/CR compared to Sham (*P<0.05), but HS+FFP restored LBF to Sham levels (*P<0.05).  Lung pathology showed increased neutrophil infiltration in the HS/CR group compared to Sham, which was largely prevented in the HS+FFP group. Lung ICAM-1 expression was increased in HS/CR (*P<0.05) but decreased in HS+FFP (*P<0.05). Hematuria was noted in 4 out of 8 HS/CR rats that received FFP. 

Conclusion: Resuscitation with FFP when used with blood RES minimized inflammatory changes in the lung.  Liver blood flow was also improved by resuscitation with FFP, which might support improved lung status.  These results suggest that FFP can be used in place of aggressive intravenous saline resuscitation in hemorrhagic shock.  The use of FFP has found favor in human patients and these studies support that use.