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Estradiol Modulation of Brain Death Effects on Heart Tissue in Female Rats
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A4733 - Estradiol Modulation of Brain Death Effects on Heart Tissue in Female Rats
Author Block: R. Armstrong Junior, F. Y. Ricardo-da-Silva, L. J. L. Basilio, M. S. Vidal, P. Sannomiya, L. F. P. Moreira, A. C. Breithaupt-Faloppa; Laboratório Cirúrgico de Pesquisa Cardiovascular, Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
Rationale: Clinical evidence indicates that female donor hearts lead to higher early mortality in male recipients. In a previous study we showed that female rats submitted to brain death (BD) present higher inflammatory response in the heart in comparison to male. In this study, we aimed to investigate the estradiol influence in the heart inflammatory mediators release and cell apoptosis in female rats.Methods: Female Wistar Rats (8 weeks) were submitted to BD by intracranial balloon rapid inflation and maintained for 6h. The treated group received 17β-estradiol (E2 50μ/mL i.v 2mL/h immediately after BD induction). Sham-operated (S) rats were used as controls. Heart myeloperoxidase activity (MPO) and vascular permeability (HVP) were assessed. IL-1β was quantified in serum using multiplex. The expression of BCL-2 and Caspase-3 were evaluated on heart sections using immunohistochemistry. Besides, heart fragments were maintained for 24h in culture and IL-1 β release were assessed in medium samples by ELISA. Results: BD induced a significant increase of Caspase-3 expression which was reduced by E2 treatment (S: 9.97 ±2.88, BD: 40.76 ±10.4, E2: 9.23 ±2.64 stained area/total area x10-3; p=0.002). In parallel, E2 was be able to significantly increase BCL-2 expression (S: 100.6±27.15, BD: 100.5 ±19.37, E2: 158.3 ±14.12 stained area/total area x10-3; p=0.034). Regarding inflammatory parameters, heart MPO activity was not altered by either BD or E2 (S: 0.946±0.073, BD: 0.894±0.078, E2: 0.989±0.128 D.O.; p=0.779). HVP was found augmented after BD and no effect of E2 was observed (S: 738±80, BD: 1099±92, E2: 1057±186 pg/mL/mg dry weight; p=0.099). IL-1β concentration was found elevated in serum and in medium with a tendency of reduction by estradiol treatment (Serum - S: 58.13±14, BD: 124±31, E2: 65±19 pg/mL, p=0.087; Medium - S: 14±3, BD: 34±12, E2: 17±4.66 pg/mL/mg dry weight, p=0.69).Conclusion: Our data show that estradiol reduces heart cell apoptosis and modulate the local and systemic release of IL-1β on brain dead female rats. Further investigation on estradiol effects after BD may provide clues for therapies aiming the improvement of donor organ preservation.
Author Block: R. Armstrong Junior, F. Y. Ricardo-da-Silva, L. J. L. Basilio, M. S. Vidal, P. Sannomiya, L. F. P. Moreira, A. C. Breithaupt-Faloppa; Laboratório Cirúrgico de Pesquisa Cardiovascular, Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
Rationale: Clinical evidence indicates that female donor hearts lead to higher early mortality in male recipients. In a previous study we showed that female rats submitted to brain death (BD) present higher inflammatory response in the heart in comparison to male. In this study, we aimed to investigate the estradiol influence in the heart inflammatory mediators release and cell apoptosis in female rats.Methods: Female Wistar Rats (8 weeks) were submitted to BD by intracranial balloon rapid inflation and maintained for 6h. The treated group received 17β-estradiol (E2 50μ/mL i.v 2mL/h immediately after BD induction). Sham-operated (S) rats were used as controls. Heart myeloperoxidase activity (MPO) and vascular permeability (HVP) were assessed. IL-1β was quantified in serum using multiplex. The expression of BCL-2 and Caspase-3 were evaluated on heart sections using immunohistochemistry. Besides, heart fragments were maintained for 24h in culture and IL-1 β release were assessed in medium samples by ELISA. Results: BD induced a significant increase of Caspase-3 expression which was reduced by E2 treatment (S: 9.97 ±2.88, BD: 40.76 ±10.4, E2: 9.23 ±2.64 stained area/total area x10-3; p=0.002). In parallel, E2 was be able to significantly increase BCL-2 expression (S: 100.6±27.15, BD: 100.5 ±19.37, E2: 158.3 ±14.12 stained area/total area x10-3; p=0.034). Regarding inflammatory parameters, heart MPO activity was not altered by either BD or E2 (S: 0.946±0.073, BD: 0.894±0.078, E2: 0.989±0.128 D.O.; p=0.779). HVP was found augmented after BD and no effect of E2 was observed (S: 738±80, BD: 1099±92, E2: 1057±186 pg/mL/mg dry weight; p=0.099). IL-1β concentration was found elevated in serum and in medium with a tendency of reduction by estradiol treatment (Serum - S: 58.13±14, BD: 124±31, E2: 65±19 pg/mL, p=0.087; Medium - S: 14±3, BD: 34±12, E2: 17±4.66 pg/mL/mg dry weight, p=0.69).Conclusion: Our data show that estradiol reduces heart cell apoptosis and modulate the local and systemic release of IL-1β on brain dead female rats. Further investigation on estradiol effects after BD may provide clues for therapies aiming the improvement of donor organ preservation.
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