INFLUENCE OF GENDER ON ALLOGRAFT-REJECTION IN A RAT-HEART TRANSPLANT MODEL

Background: Clinical studies have reported increased rejection in fema le heart transplant recipients. Conflicting data exist as to whether r ejection is increased with male donors or female donors in these femal e recipients. Methods: We investigated in this study allograft rejecti on in four sets of gender combinations with and without immunosuppress ion with the use of a heterotopic rat heart transplant model: male don or heart to female recipient, female donor heart to female recipient, male donor to male recipient, and female donor to male recipient. To e xamine the possible effect of androgens as an immunosuppressant, we or chiectomized a group of male recipient rats before transplantation. Th e rats that were not immunosuppressed were evaluated for length of gra ft survival (palpation). In the immunosuppressed rats (cyclosporine, 1 0 mg/kg x 7 days) in each gender combination half of the grafts were e valuated for length of survival (palpation) and half for cellular reje ction grade at day 14 (microscopy). Results: When rats that underwent transplantation were not immunosuppressed, no difference in graft surv ival time was found among the four sets of gender combinations. With i mmunosuppression, median graft survival time was 23 days in female rec ipients versus 32 days in male recipients (p < 0.05). Mean cellular re jection grade at day 14 was 2.95 +/- 0.7 in female recipients and 0.8 +/- 0.4 in male recipients (p < 0.01). No significant difference was f ound in graft survival time or cellular rejection grade with respect t o donor gender. The graft survival times and cellular rejection grades of the male rats undergoing orchiectomy were not different from those of normal male recipients (p = NS). Cyclosporine levels on day 7 in b oth male and female recipients were high, female levels (1039 +/- 411 ng/ml) were less than male levels (2029 +/- 379 ng/ml) (p < 0.01). Con clusions: Female recipients of heterotopic rat heart transplants had s horter graft survival time and increased Cellular rejection as compare d with male recipients. Donor gender had no influence on graft surviva l or cellular rejection grade. Orchiectomy had no influence on graft s urvival time or grade of rejection. Results of this model suggest that female recipients may require increased immunosuppression and rejecti on surveillance, regardless of donor gender.