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.
Claridge
J A
JA
Department of Surgery, Trauma Research Laboratory, University of Virginia Health System, Charlottesville, VA 22908-0709, USA.
Weed
A C
AC
Enelow
R
R
Young
J S
JS
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