Elsevier

Surgery

Volume 137, Issue 1, January 2005, Pages 56-65
Surgery

Original communication
Sex hormones modulate distant organ injury in both a trauma/hemorrhagic shock model and a burn model

https://doi.org/10.1016/j.surg.2004.04.037Get rights and content

Background

Emerging data suggest a gender dimorphism in resistance and susceptibility to distant organ injury after mechanical and thermal trauma. The aim of this study was to determine the role that testosterone and estradiol play in modulating resistance or susceptibility to distant organ injury, and whether their effects were associated with differences in the production of nitric oxide.

Methods

Adult male, female, castrated male, and ovariectomized female Sprague-Dawley rats were given intraperitoneal pentobarbital sodium anesthesia and subjected to trauma/sham shock or trauma/hemorrhagic shock (T/HS). A second set of animals were subjected to a 40% total body surface area, third-degree burn or sham burn. At 3 hours after resuscitation, plasma levels of nitrite/nitrate were measured, and the extent of lung injury (permeability to Evans Blue dye and neutrophil sequestration by myeloperoxidase) and intestinal injury (morphology) were determined.

Results

Proestrus females showed resistance to lung and gut injury after both T/HS and burns, and had low levels of nitrite/nitrate production. This resistance to injury was abrogated by ovariectomy with an associated increase in nitric oxide production. Males showed increased lung and gut injury after both T/HS and burns associated with increased production of nitrite/nitrate. Castration decreased susceptibility to both lung and gut injury, and decreased production of nitrite/nitrate. A correlation was noted between intestinal and lung injury, and both intestinal and lung injury correlated with plasma nitrite/nitrate levels.

Conclusions

Male sex hormones potentiate, while female hormones reduce T/HS and burn-induced lung and gut injury. Production of nitric oxide is associated with increased lung and gut injury after T/HS and burns.

Section snippets

Experimental design

The overall aim of this study was to determine the role that male (testosterone) and female (β-estradiol) sex hormones play in the resistance and/or susceptibility to T/HS-induced and burn-induced intestinal or lung injury. To isolate the effects of sex hormones from other gender-related factors, we compared castrated and ovariectomized rats to normal male and proestrus female rats in 2 separate models: T/HS and burns. The T/HS model consisted of a laparotomy (trauma) and hemorrhage (30 mm Hg ×

Results

The preburn or sham-burn sex hormone plasma levels summarized in Table I validate the vaginal cytologic determination that the female rats were in the proestrus stage of the cycle. They also documented that the sex hormones were reduced as expected in the castrated and ovariectomized animals.

As previously reported,14 T/HS caused an increase in lung permeability and pulmonary neutrophil sequestration in male but not proestrus female rats (Fig 1). The increased susceptibility of the male rats to

Discussion

Since castration decreased and ovariectomy increased both T/HS- and burn-induced lung and gut injury, one major observation of the current study is that both male and female sex hormones modulate the extent of gut and lung injury, with testosterone contributing to injury and estradiol being protective. This was most apparent in the magnitude of T/HS-induced or burn-induced lung injury since the levels of lung permeability and neutrophil sequestration were similar between the castrated male and

Conclusion

The results of the current study demonstrate that male sex hormones potentiate, while female sex hormones reduce lung and gut injury in rats subjected to T/HS or burn injury. The results are also consistent with the concept that both T/HS-induced and burn-induced gut injuries contribute to lung injury and that increased nitric oxide production is associated with increased susceptibility to organ injury. The clinical implications of these observations utilizing the nonlethal T/HS and burn models

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    Supported by NIH grant GM59841.

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