Evaluation of the effects of gender and estradiol treatment on the intestinal microcirculation during experimental sepsis

Abstract

Intestinal barrier dysfunction plays an important role in sepsis. Females may tolerate sepsis better than males, which could be due to the relative resistance of the female intestine to gut injury and inflammation when subjected to sepsis.In this study the intestinal microcirculation was investigated in 50 female and 40 male rats divided in to 9 groups of 10 animals. Male and female rats were subjected to sham CASP (colon ascendens stent peritonitis). We induced experimental sepsis (CASP) in another two groups of male and female rats. The role of the estradiol treatment was evaluated both in male and ovariectomized female rats. Female rats were subjected to sham ovariectomy 3weeks before sham CASP. Male and ovariectomized female rats were treated with estradiol (10mg/kg estradiol in rizinus oil immediately and 12h following CASP). Another two groups of male and ovariectomized female rats received placebo oil treatment. To evaluate the effects of gender and estradiol treatment on the microvascular perfusion during sepsis, intravital microscopy was performed twenty-four hours after sham CASP or CASP surgery, which permits the in vivo determination of leukocyte–endothelial cell interaction (rolling leukocytes and adherent leukocytes) and the measurement of functional capillary density (FCD), which served as the measure of quality of microvascular perfusion.We found that there was gender difference mainly in the leukocyte endothelial interaction rather than the functional capillary density (FCD), in which male showed significant increases (P<0.05) both in the leukocyte adhesion and rolling leukocytes in submucosal venules (V1 and V3) in comparison to female rats. (Leukocyte adhesion: V1 107.1±49.2n/mm2; V3 112.3±68.1n/mm2) (Rolling leukocytes:V1 16.2±10.3n/min; V3 8.4±8.2n/min). In addition estradiol replacement in ovariectomized female and male rats induced significant decreases (P<0.05) in the leukocyte adhesion and rolling (V1 and V3) with a significant increase in the muscular FCD in comparison to the corresponding placebo treated groups. (Leukocyte adhesion: V1 60±31n/mm2; V3 78.11±37.6n/mm2) (Rolling leukocytes: V1 13.4±8.9n/min; V3 5.8±7.4n/min) (Longitudinal muscular FCD (cm/cm2): in ovariectomized female rats 107.1±12.2; in male rats 106.2±15.3) (Circular muscular FCD (cm/cm2): in ovariectomized female rats: 84.8±14.2; in male rats: 86.1±15.3).We conclude that gender difference in the leukocyte endothelial interaction could explain the resistance of female intestine to injury, and that estradiol treatment could improve the intestinal microcirculation through its effects on the leukocyte endothelial interaction and the FCD both in male and ovariectomized female rats.