The effect of estrogen on hepatic microcirculation after ischemia/reperfusion

Gender dimorphism in clinical manifestation of sepsis, hemorrhage, and trauma is still under investigation. Several experimental studies have indicated a protective effect of estrogen. Nonetheless, the effect of gender on hepatic ischemia/reperfusion remains controversially discussed, and the influence of estrogen is still unclear. In the present study, we investigated whether hepatic ischemia/reperfusion (I/R) injury is gender-dependent and if hepatic microvascular reperfusion injury can be prevented by estrogen.

Eight female and eight male Sprague-Dawley rats were subjected to 90 min left lobar ischemia followed by 60 min reperfusion. Additional six males were pretreated with 17beta-estradiol 24 h before I/R. Six female and six male rats served as nonischemic sham animals. By means of intravital microscopy, sinusoidal perfusion, leukocyte-endothelial cell interaction, and Kupffer cell activity were analyzed. Finally, arterial blood and liver tissue samples were taken for histomorphological analysis and liver enzyme determination.

After hepatic ischemia/reperfusion, animals revealed a significant gender-specific impairment of hepatic microcirculation, whereas Kupffer cell depression, sinusoidal perfusion failure, leukocyte-endothelial cell interaction within post sinusoidal venules, and parenchymal liver cell damage were more pronounced in male animals. Pretreatment with estrogen caused a normalization of Kupffer cell dysfunction and an amelioration of sinusoidal perfusion failure and venular leukocyte-endothelial cell interaction. However, estrogen did not protect from manifestation of post ischemic parenchymal cell damage.

Hepatic ischemia and reperfusion generate a gender-specific occurrence of microvascular injury, which seems to be partially mediated by estrogen. However, additional factors may contribute to the initial post ischemic parenchymal cell damage.