The effect of estrogen on hepatic microcirculation after ischemia/reperfusion.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Burkhardt
M
M
Department of Trauma, Hand and Reconstructive Surgery, Saarland University Hospital, Kirrberger Strasse, 66421 Homburg/Saar, Germany. chmbur@uniklinik-saarland.de
Slotta
J E
JE
Garcia
P
P
Seekamp
A
A
Menger
M D
MD
Pohlemann
T
T
D000818:Animals; D002448:Cell Adhesion; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D007728:Kupffer Cells / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D008102:Liver Circulation; D008297:Male; D008833:Microcirculation; D010587:Phagocytosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012737:Sex Factors
D004958:Estradiol