Lower liver transplant success in females: gender differences in metabolic response to global ischemia

Impact of Female Sex Hormones on Liver Tissue Lactic Acidosis During Ischemia

“…Mechanisms for the previously described sex differences in liver lactic acidosis during ischemia (14) have been clarified in this study. Specifically, 17 ␤-estradiol resulted in the accumulation of significantly more lactate and H ϩ , which was blunted in the presence of progesterone.…”

“…4) (14). By 10 min of ischemia H ϩ levels had significantly increased (PϽ0.001) similarly in all groups except EϩP, which displayed a trend to higher H ϩ (Pϭ0.054).…”

“…Thus the current safe limits of tolerance of the liver to warm ischemia are unclear and warrant further investigation. Recently identified sex differences in the metabolic responses to warm ischemia in rat livers (14) suggest that sex should be taken into account when constructing guidelines on acceptable warm ischemia times. Whether sex hormones underlie these sex differences has not been explored and may provide additional insight into the metabolic contributions to the length of time that the liver can safely be exposed to warm ischemia.…”

“…Recent experimental evidence has shown that female rats develop a greater degree of hepatic tissue lactic acidosis during warm ischemia than males (14), which may provide a potential metabolic explanation for the worse outcome in recipients of livers from female donors, by suggesting that female livers sustain a greater degree of injury from the increased acidosis. It also suggests that the safe limits of tolerance of the liver to warm ischemia in DCD donors may be less in females than in males.…”

Improved renal ischemia tolerance in females influences kidney transplantation outcomes

“…Generally, there is consensus that female sex conveys greater tolerance of, or protection from, IRI relative to the male sex. Investigations have focused on the effects of estrogen and testosterone on the intrinsic tissue tolerance of ischemia through differential expression of oxidative scavengers, HSPs, or other mediators (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Moreover, a number of reports describe sex differences in the development of chronic injury patterns in animal transplant models (15,24,25).…”