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 de velopment of organ failure after traumatic injury. We evaluated the effects of exploratory laparotomy (EL) as a second hit on mice after hemorrhage an d resuscitation (H/R), Our hypothesis was that mice exposed to prior Hm mou ld demonstrate more evidence of acute lung injury (ALI), as well as an augm ented cytokine response, than mice exposed to WR 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 hem orrhage), followed 5 days later by EL, were labeled as the EL group; and mi ce 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) an d tumor necrosis factor-alpha (TNF-alpha) were assayed at 1 and 4 hours aft er the injury stimuli. Results: Evaluation of the change in pulmonary function after 24 hours demo nstrated that EL alone induces a significant decrease in pulmonary function , whereas two-hit mice did not exhibit a potentiated response. Alveolar fun ction was significantly degraded in the EL group compared with all other gr oups (p < 0.0001), TNF-<alpha> did not change after any injury at any time. However, evaluation of IL-6 levels demonstrated a substantial increase aft er H/R, EL, and H/R + EL compared with baseline and at 1 hour. Comparison o f the three groups at 4 hours did not demonstrate any differences in serum concentrations of IL-6. Histologic evaluation lungs demonstrated that the m ost severe lung injury was seen in the EL mice. Conclusion: It would appear that serum TNF-alpha has little impact on the p athogenesis of ALI after El,, whereas serum IL-6 may be more important. Exp loratory 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.