Laparotomy potentiates cytokine release and impairs pulmonary function after hemorrhage and resuscitation in mice.
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.


CONCLUSIONS
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.
Department of Surgery, Trauma Research Laboratory, University of Virginia Health System, Charlottesville, VA 22908-0709, USA.
J A
JA
Claridge
A C
AC
Weed
R
R
Enelow
J S
JS
Young
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015850:Interleukin-6 / Q000032:analysis*; D007813:Laparotomy; D051379:Mice; D008815:Mice, Inbred Strains; D010993:Plethysmography, Whole Body; D011650:Pulmonary Alveoli / Q000503:physiopathology; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics; D012771:Shock, Hemorrhagic / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha