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.
Department of Trauma, Hand and Reconstructive Surgery, Saarland University Hospital, Kirrberger Strasse, 66421 Homburg/Saar, Germany. chmbur@uniklinik-saarland.de
M
M
Burkhardt
J E
JE
Slotta
P
P
Garcia
A
A
Seekamp
M D
MD
Menger
T
T
Pohlemann
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