Sex differences in kidney and lung status in an animal model of brain death

Background

In transplantation, sex-mismatched procedures correlate with poorer outcomes. Previous research has indicated that females respond worst to Brain Death (BD) and that organ damage varies with the speed of BD induction. The authors aimed to investigate the effects of slow BD-induction on lung and kidney responses in male and female rats.

Methods

Males and female rats were subjected to slow induction of BD and kept for 4h. Blood gas samples were taken at 0 h and 4h. At 4 h, blood, urine and tissue samples were collected. IL-1β was measured in plasma, lung homogenate and lung culture. IL-6 was quantified in plasma, lung culture, and kidney homogenate. Leukocyte infiltration/activation was evaluated. Biochemical analyses of creatinine were performed in the plasma. Naïve animals were used as controls.

Results

Males presented reduced testosterone levels after 4h. Females presented reduced progesterone, whereas estradiol remained similar at 0 h and 4h. Compared with Naive, BD-groups presented increased plasma IL-1β and IL-6. Males and females presented reduced pO₂ after BD, with females presenting even lower values at 4h. In lung tissue, males presented increased expression of IL-1β, whereas IL-1β was elevated in females in lung culture. Females presented increased cell infiltration/activation. In the kidney, males presented increased plasma creatinine, increased expression of caspase-3, and increased leukocyte migration to renal tissue than females.

Conclusions

The authors observed an organ and sex-dependent response to the slow-induction of BD. These results suggest that management strategies should consider the sex of the donor to achieve the best treatment, improving graft quality.