TY - JOUR
T1 - Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion
AU - Ricardo-da-Silva, Fernanda Yamamoto
AU - Armstrong-Jr, Roberto
AU - Ramos, Mayara Munhoz de Assis
AU - Vidal-Dos-Santos, Marina
AU - Jesus Correia, Cristiano
AU - Ottens, Petra J.
AU - Moreira, Luiz Felipe Pinho
AU - Leuvenink, Henri G.D.
AU - Breithaupt-Faloppa, Ana Cristina
N1 - Publisher Copyright:
© 2024. The Author(s).
PY - 2024/1/29
Y1 - 2024/1/29
N2 - 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.
AB - 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.
KW - Brain death
KW - Donor
KW - Ex vivo lung perfusion
KW - Lung
KW - Rat
KW - Sex
UR - http://www.scopus.com/inward/record.url?scp=85184344656&partnerID=8YFLogxK
U2 - 10.1186/s13293-024-00581-8
DO - 10.1186/s13293-024-00581-8
M3 - Article
C2 - 38287395
AN - SCOPUS:85184344656
SN - 2042-6410
VL - 15
JO - Biology of Sex Differences
JF - Biology of Sex Differences
M1 - 11
ER -