Vidal-Dos-Santos Marina, Armstrong-Jr Roberto, van Zil Maryna, Ricardo-da-Silva Fernanda Yamamoto, da Anunciação Lucas Ferreira, de Assis Ramos Mayara Munhoz, Correia Cristiano de Jesus, Ottens Petra J, Moreira Luiz Felipe Pinho, Leuvenink Henri G D, Breithaupt-Faloppa Ana Cristina
Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil; Department of Surgery, University Medical Centre Groningen, University of Groningen, The Netherlands.
Department of Surgery, University Medical Centre Groningen, University of Groningen, The Netherlands.
Clinics (Sao Paulo). 2025 Mar 26;80:100623. doi: 10.1016/j.clinsp.2025.100623. eCollection 2025.
In transplantation, sex-mismatched procedures correlate with poorer outcomes. Previous research has indicated that females respond worst to Brain Death (BD) and that organ damage varies with the speed of BD induction. The authors aimed to investigate the effects of slow BD-induction on lung and kidney responses in male and female rats.
Males and female rats were subjected to slow induction of BD and kept for 4h. Blood gas samples were taken at 0 h and 4h. At 4 h, blood, urine and tissue samples were collected. IL-1β was measured in plasma, lung homogenate and lung culture. IL-6 was quantified in plasma, lung culture, and kidney homogenate. Leukocyte infiltration/activation was evaluated. Biochemical analyses of creatinine were performed in the plasma. Naïve animals were used as controls.
Males presented reduced testosterone levels after 4h. Females presented reduced progesterone, whereas estradiol remained similar at 0 h and 4h. Compared with Naive, BD-groups presented increased plasma IL-1β and IL-6. Males and females presented reduced pO after BD, with females presenting even lower values at 4h. In lung tissue, males presented increased expression of IL-1β, whereas IL-1β was elevated in females in lung culture. Females presented increased cell infiltration/activation. In the kidney, males presented increased plasma creatinine, increased expression of caspase-3, and increased leukocyte migration to renal tissue than females.
The authors observed an organ and sex-dependent response to the slow-induction of BD. These results suggest that management strategies should consider the sex of the donor to achieve the best treatment, improving graft quality.
在移植手术中,性别不匹配的手术与较差的预后相关。先前的研究表明,女性对脑死亡(BD)的反应最差,并且器官损伤随BD诱导速度的不同而变化。作者旨在研究缓慢诱导BD对雄性和雌性大鼠肺和肾反应的影响。
对雄性和雌性大鼠进行缓慢的BD诱导,并维持4小时。在0小时和4小时采集血气样本。在4小时时,收集血液、尿液和组织样本。检测血浆、肺匀浆和肺培养物中的白细胞介素-1β(IL-1β)。定量检测血浆、肺培养物和肾匀浆中的白细胞介素-6(IL-6)。评估白细胞浸润/活化情况。对血浆中的肌酐进行生化分析。以未处理的动物作为对照。
4小时后,雄性大鼠的睾酮水平降低。雌性大鼠的孕酮水平降低,而雌二醇在0小时和4小时保持相似。与未处理组相比,BD组的血浆IL-1β和IL-6升高。BD后,雄性和雌性大鼠的动脉血氧分压(pO)均降低,雌性大鼠在4小时时的值更低。在肺组织中,雄性大鼠的IL-1β表达增加,而雌性大鼠在肺培养物中的IL-1β升高。雌性大鼠的细胞浸润/活化增加。在肾脏中,雄性大鼠的血浆肌酐升高,半胱天冬酶-3(caspase-3)的表达增加,白细胞向肾组织的迁移比雌性大鼠更多。
作者观察到对缓慢诱导BD存在器官和性别依赖性反应。这些结果表明,管理策略应考虑供体的性别以实现最佳治疗效果,提高移植物质量。