As many as 500 children undergo liver transplantation in the US each year. Data on pediatric liver transplantation shows that the outcomes are worse for children who receive organs from female donors.
Clinical studies have shown that, compared to males receiving male livers, males receiving female livers experience a higher incidence of early complications and almost twice the amount of graft losses.
During liver transplantation, the organ undergoes a period of no-flow ischemia, or complete lack of blood flow, and therefore must rely in part on internal nutrient stores to produce energy anaerobically (without oxygen). The end-products of this process (anaerobic metabolism) are lactate and hydrogen ions (H+) which can accumulate in the liver cells during ischemia leading to detrimental affects.
Thus, to better understand the gender effects of infant liver transplantation, the researchers examined anaerobic end-product accumulation in newborn male and female livers during no-flow ischemia. Baseline liver biopsies were harvested from anesthetized three-day-old male (n=4) and female (n=6) piglets and immediately afterward the liver was excised and placed in a normothermic bath for 45 minutes. Biopsies were then taken at 15, 30, and 45 minutes of ischemia. All biopsies were analyzed for anaerobic end-products lactate and hydrogen ion (H+) content.
The research team found that both male and female livers showed similar low levels of both lactate and H+ at baseline. But during ischemia, newborn female livers accumulated a greater amount of H+ compared to males. This difference persisted throughout the entire ischemic period. The results were paralleled by a similar greater and more rapid accumulation of lactate in newborn female livers, a difference that was sustained throughout the ischemic period.
Based on these findings and other considerations, the researchers concluded that:
* the newborn female liver developed a greater and more rapid tissue acidosis compared to males during normothermic ischemia, which may be due in part to greater anaerobic glycolysis in females; and
* more rapid lactic acidosis in newborn female livers may result in greater metabolic damage during ischemia.
According to Quaglietta, the lead researcher, ?These findings may offer a potential explanation for pediatric studies reporting worse outcome of recipients receiving livers from female donors.?