Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion.

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Biology of Sex Differences Pub Date : 2024-01-29 DOI:10.1186/s13293-024-00581-8
Fernanda Yamamoto Ricardo-da-Silva, Roberto Armstrong-Jr, Mayara Munhoz de Assis Ramos, Marina Vidal-Dos-Santos, Cristiano Jesus Correia, Petra J Ottens, Luiz Felipe Pinho Moreira, Henri G D Leuvenink, Ana Cristina Breithaupt-Faloppa
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Abstract

Background: Ex vivo lung perfusion (EVLP) is a useful tool for assessing lung grafts quality before transplantation. Studies indicate that donor sex is as an important factor for transplant outcome, as females present higher inflammatory response to brain death (BD) than males. Here, we investigated sex differences in the lungs of rats subjected to BD followed by EVLP.

Methods: Male and female Wistar rats were subjected to BD, and as controls sham animals. Arterial blood was sampled for gas analysis. Heart-lung blocks were kept in cold storage (1 h) and normothermic EVLP carried out (4 h), meanwhile ventilation parameters were recorded. Perfusate was sampled for gas analysis and IL-1β levels. Leukocyte infiltration, myeloperoxidase presence, IL-1β gene expression, and long-term release in lung culture (explant) were evaluated.

Results: Brain dead females presented a low lung function after BD, compared to BD-males; however, at the end of the EVLP period oxygenation capacity decreased in all BD groups. Overall, ventilation parameters were maintained in all groups. After EVLP lung infiltrate was higher in brain dead females, with higher neutrophil content, and accompanied by high IL-1β levels, with increased gene expression and concentration in the culture medium (explant) 24 h after EVLP. Female rats presented higher lung inflammation after BD than male rats. Despite maintaining lung function and ventilation mechanics parameters for 4 h, EVLP was not able to alter this profile.

Conclusion: In this context, further studies should focus on therapeutic measures to control inflammation in donor or during EVLP to increase lung quality.

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男性与女性在脑死亡模型后的炎症反应,然后进行体外肺灌注。
背景:体外肺灌注(EVLP)是移植前评估肺移植物质量的有效工具。研究表明,供体性别是影响移植结果的一个重要因素,因为雌性大鼠对脑死亡(BD)的炎症反应高于雄性大鼠。在此,我们研究了接受脑死亡后EVLP的大鼠肺部的性别差异:方法:雄性和雌性 Wistar 大鼠均接受脑死亡治疗,假大鼠作为对照组。抽取动脉血进行气体分析。将心肺块冷藏(1 小时)并进行常温 EVLP(4 小时),同时记录通气参数。抽取灌注液进行气体分析和检测 IL-1β 水平。对白细胞浸润、髓过氧化物酶的存在、IL-1β基因表达以及肺培养(外植体)中的长期释放进行了评估:结果:与脑死亡男性相比,脑死亡女性在BD后肺功能较低;然而,在EVLP期结束时,所有BD组的氧合能力都下降了。总体而言,所有组的通气参数都保持不变。EVLP后,脑死亡雌性大鼠的肺浸润程度更高,中性粒细胞含量更高,同时IL-1β水平也很高,EVLP 24小时后,培养基(外植体)中的基因表达和浓度都有所增加。与雄性大鼠相比,雌性大鼠在 BD 后的肺部炎症程度更高。尽管肺功能和通气力学参数维持了 4 小时,但 EVLP 无法改变这种情况:结论:在这种情况下,进一步的研究应侧重于控制供体或 EVLP 期间炎症的治疗措施,以提高肺的质量。
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来源期刊
Biology of Sex Differences
Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY
CiteScore
12.10
自引率
1.30%
发文量
69
审稿时长
14 weeks
期刊介绍: Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.
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