Anemia Recovery After Lung Contusion, Hemorrhagic Shock and Chronic Stress is Sex-Specific

Gwendolyn Gillies; Jennifer Munley; Lauren Kelly; Preston Coldwell; Kolenkode Kannan; Letitia Bible; Philip Efron; Alicia Mohr

Severe trauma and hemorrhagic shock lead to anemia that persists despite resuscitation and cessation of bleeding. Biologic sex is known to modulate inflammatory responses following trauma and hemorrhagic shock, however, the impact of sex on anemia recovery after injury remains unknown. The aim of this study was to identify sex-specific differences in anemia recovery following injury, hemorrhagic shock, and chronic stress.

We hypothesized that female sex, in a rodent model of polytrauma, is associated with improved anemia recovery following injury, hemorrhagic shock, and chronic stress.

Male and proestrus female Sprague-Dawley rats (n=8/group) aged 9-11 weeks were subjected to lung contusion and hemorrhagic shock (LCHS) or LCHS with daily chronic stress (LCHS/CS) and compared to naïve controls. Weight change, serum iron, bone marrow erythroid progenitor (CFU-GEMM and BFU-E) colony growth and liver transcription of bone morphogenic protein (BMP)4 and BMP6 were measured on day 7. ANOVA comparisons between male and female groups and between naïve, LCHS, and LCHS/CS within each sex were performed with GraphPad. Significance was defined as *p<0.05 vs. naïve; **p<0.05 vs. male counterpart.

Males lost more weight following LCHS and LCHS/CS compared to naïve (-1.338%* and -3.446%* vs. +7.228%), while female LCHS rats started to recover weight by day 7 compared to naïve. Hemoglobin levels in male LCHS and LCHS/CS rats remained lower at day 7 compared to naïve males and females following LCHS and LCHS/CS. Male LCHS and LCHS/CS rats had reduced CFU-GEMM and BFU-E when compared to naïve and females following LCHS and LCHS/CS. Females had higher serum iron than males in naïve, LCHS and LCHS/CS groups (387** vs. 190 ug/dL, 328* vs. 245 ug/dL, 272** vs. 186 ug/dL). Liver transcription of BMP4 and BMP6 was significantly lower in female LCHS and LCHS/CS groups compared to male LCHS and LCHS/CS.

Following trauma with or without chronic stress, females demonstrate improved recovery from anemia, reduced weight loss, and reduced suppression of bone marrow erythroid progenitor growth compared to males. These findings suggest that sex is an important variable that may influence outcomes after severe trauma and critical illness.