Gut injury and gut-induced lung injury after trauma hemorrhagic shock is gender and estrus cycle specific in the rat

Background: The purpose of this study was to test the hypothesis that trauma-hemorrhagic shock (T/HS)-induced gut and lung injury is modulated by gender and the stage of the estrus cycle at the time of injury. Methods: We compared the incidence and magnitude of gut and lung injury in male and female rats subjected to a laparotomy (trauma) followed by 90 minutes of shock (mean arterial pressure, 30 mm Hg) (T/HS) or sham shock. Results: Lung injury and pulmonary neutrophil sequestration as well as gut injury were increased after T/HS in the diestrus female and the male rats, but not in the estrus or proestrus female rats. Although T/HS caused gut and lung injury in the male and the female diestrus rats, the magnitude of injury was less in the female diestrus than in the male rats (p < 0.05). A strong correlation was found between intestinal villous injury and lung injury as well as between gut injury and pulmonary leukosequestration in the female rats subjected to T/HS (p < 0.0001). Plasma nitric oxide levels were approximately two- to threefold higher in the male and the diestrus female rats subjected to T/HS than in other groups (p < 0.05), and a high degree of correlation (r(2) = 0.68, p < 0.0001) was found between villous injury and plasma nitric oxide levels. Ileal constitutive nitric oxide synthase (NOS) and inducible NOS (iNOS) activity was measured. Ileal constitutive NOS activity was similar between the groups, but iNOS activity was three- to fourfold higher in the T/HS male rats than in the sham shock or the T/HS proestrus groups (P < 0.01). Conclusion: Gender and estrus cycle stage influence susceptibility to T/HS-induced gut and lung injury. This difference in susceptibility to organ injury was associated with increased plasma nitric oxide levels and increased ileal iNOS activity.