Document Detail

Laparotomy potentiates cytokine release and impairs pulmonary function after hemorrhage and resuscitation in mice.
MedLine Citation:
PMID:  11242288     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The two-hit theory has emerged as a mechanism to explain the development of organ failure after traumatic injury. We evaluated the effects of exploratory laparotomy (EL) as a second hit on mice after hemorrhage and resuscitation (H/R). Our hypothesis was that mice exposed to prior H/R would demonstrate more evidence of acute lung injury (ALI), as well as an augmented cytokine response, than mice exposed to H/R or EL alone. METHODS: Three groups of mice were examined. Mice undergoing H/R alone were labeled as the H/R group. Mice undergoing sham H/R (cannulation but no hemorrhage), followed 5 days later by EL, were labeled as the EL group; and mice undergoing H/R, followed 5 days later by an EL, were labeled as the H/R + EL, or two-hit, group. Respiratory function was determined by using whole-body plethysmography and lung gas diffusion. Serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assayed at 1 and 4 hours after the injury stimuli. RESULTS: Evaluation of the change in pulmonary function after 24 hours demonstrated that EL alone induces a significant decrease in pulmonary function, whereas two-hit mice did not exhibit a potentiated response. Alveolar function was significantly degraded in the EL group compared with all other groups (p < 0.0001). TNF-alpha did not change after any injury at any time. However, evaluation of IL-6 levels demonstrated a substantial increase after H/R, EL, and H/R + EL compared with baseline and at 1 hour. Comparison of the three groups at 4 hours did not demonstrate any differences in serum concentrations of IL-6. Histologic evaluation lungs demonstrated that the most severe lung injury was seen in the EL mice. CONCLUSION: It would appear that serum TNF-alpha has little impact on the pathogenesis of ALI after EL, whereas serum IL-6 may be more important. Exploratory laparotomy resulted in a significant change in pulmonary function. Contrary to our initial hypothesis, two-hit mice did not demonstrate more evidence of ALI and, in fact, demonstrated less lung injury than EL mice.
J A Claridge; A C Weed; R Enelow; J S Young
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of trauma     Volume:  50     ISSN:  0022-5282     ISO Abbreviation:  J Trauma     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-03-12     Completed Date:  2001-04-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376373     Medline TA:  J Trauma     Country:  United States    
Other Details:
Languages:  eng     Pagination:  244-52     Citation Subset:  AIM; IM    
Department of Surgery, Trauma Research Laboratory, University of Virginia Health System, Charlottesville, VA 22908-0709, USA.
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MeSH Terms
Disease Models, Animal*
Interleukin-6 / analysis*
Mice, Inbred Strains
Plethysmography, Whole Body
Pulmonary Alveoli / physiopathology
Respiratory Distress Syndrome, Adult / blood,  pathology,  physiopathology*
Respiratory Function Tests
Respiratory Mechanics
Shock, Hemorrhagic / blood,  pathology,  physiopathology*
Tumor Necrosis Factor-alpha / analysis*
Grant Support
1-F32-GM19960-01A1/GM/NIGMS NIH HHS
Reg. No./Substance:
0/Interleukin-6; 0/Tumor Necrosis Factor-alpha

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