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

Research has shown that gender plays a significant role in the metabolic processes of different organs and that transplanting livers of females into male or female recipients has significantly higher failure rates. To understand why, this study examined whether gender differences exist in various metabolic responses of livers to ischemia. The following metabolic liver parameters in Sprague-Dawley rats (male, n = 14; and female, n = 18) were examined; adenosine triphosphate (ATP) and lactate expressed as μmoles/g dry weight, and hydrogen ion content [H +] expressed as 10 −8 mol/L. In vivo liver biopsy specimens were compared with ischemic biopsy specimens at 3, 10, 15, 30, and 45 minutes (37°C). In vivo female ATP values (9.9 ± 0.8) were similar to males (9.8 ± 0.9) and both had early, rapid decline during ischemia reaching 20% of baseline by 10 minutes of ischemia. In contrast, male liver lactate accumulation peaked by 3 minutes and at much lower levels (35 ± 13), whereas female liver lactate peaked by 10 minutes at 71 ± 11. For the rest of the ischemic period, female livers exhibited significantly ( P < .05) greater lactate accumulation. Female liver H + levels also increased to higher levels (55 ± 10) than the male livers (37 ± 7) and this pattern was significantly ( P < .05) different from 10 minutes onward. Although livers of females ultimately have similar ATP profiles to livers of males, they experienced more rapid and greater degree of tissue lactate and H + accumulation during ischemia. Therefore, female livers have increased acidosis during ischemia, which could adversely affect transplant outcome.