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

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 inve...

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Main Authors: 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
Format: Article
Language:English
Published: BMC 2024-01-01
Series:Biology of Sex Differences
Subjects:
Online Access:https://doi.org/10.1186/s13293-024-00581-8
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author 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
author_facet 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
author_sort Fernanda Yamamoto Ricardo-da-Silva
collection DOAJ
description 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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spelling doaj.art-63a6ac079b8340ee8222e94aca304d7c2024-03-05T17:26:22ZengBMCBiology of Sex Differences2042-64102024-01-0115111310.1186/s13293-024-00581-8Male versus female inflammatory response after brain death model followed by ex vivo lung perfusionFernanda Yamamoto Ricardo-da-Silva0Roberto Armstrong-Jr1Mayara Munhoz de Assis Ramos2Marina Vidal-dos-Santos3Cristiano Jesus Correia4Petra J. Ottens5Luiz Felipe Pinho Moreira6Henri G. D. Leuvenink7Ana Cristina Breithaupt-Faloppa8Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), HC-FMUSP, Instituto Do Coração (InCor), Faculdade de Medicina da Universidade de São PauloLaboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), HC-FMUSP, Instituto Do Coração (InCor), Faculdade de Medicina da Universidade de São PauloLaboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), HC-FMUSP, Instituto Do Coração (InCor), Faculdade de Medicina da Universidade de São PauloLaboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), HC-FMUSP, Instituto Do Coração (InCor), Faculdade de Medicina da Universidade de São PauloLaboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), HC-FMUSP, Instituto Do Coração (InCor), Faculdade de Medicina da Universidade de São PauloDepartment of Surgery, University Medical Centre Groningen, University of GroningenLaboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), HC-FMUSP, Instituto Do Coração (InCor), Faculdade de Medicina da Universidade de São PauloDepartment of Surgery, University Medical Centre Groningen, University of GroningenLaboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), HC-FMUSP, Instituto Do Coração (InCor), Faculdade de Medicina da Universidade de São PauloAbstract 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.https://doi.org/10.1186/s13293-024-00581-8Brain deathDonorEx vivo lung perfusionLungRatSex
spellingShingle 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
Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion
Biology of Sex Differences
Brain death
Donor
Ex vivo lung perfusion
Lung
Rat
Sex
title Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion
title_full Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion
title_fullStr Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion
title_full_unstemmed Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion
title_short Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion
title_sort male versus female inflammatory response after brain death model followed by ex vivo lung perfusion
topic Brain death
Donor
Ex vivo lung perfusion
Lung
Rat
Sex
url https://doi.org/10.1186/s13293-024-00581-8
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