Prolonged warm ischemia exacerbated acute rejection after lung transplantation from donation after cardiac death in a mouse

Research output: Contribution to journalArticle

Abstract

Objective: In lung transplantation (LTx) from donation after cardiac death (DCD), the donor lungs are inevitably exposed to warm ischemic time (WIT) between the cardiac arrest and the initiation of cold preservation. We conducted this study to examine the effect of prolonged WIT on lung allograft rejection in a murine model of LTx from DCD. Methods: Allogeneic BALB/c → B6 LTx from DCD was performed with a WIT of 15 min (WIT15 group, n = 5) or 60 min (WIT60 group, n = 5). Recipients were immunosuppressed by perioperative costimulatory blockade. The lung allografts were analyzed by histology and flow cytometry on day 7 after the LTx. Results: Histologically, the rejection grade in the WIT60 group was significantly higher than that in the WIT15 group (3.4 ± 0.4 vs. 2.2 ± 0.2, P = 0.0278). Moreover, the intragraft CD8+ to CD4+ T cell ratio in the WIT60 group was significantly higher than that in the WIT15 group (2.3 ± 0.12 vs. 1.2 ± 0.11, P < 0.0001). Conclusions: Prolonged WIT could exacerbate the severity of lung allograft rejection after LTx from DCD. Minimization of the WIT could improve the outcomes after LTx from DCD.

Original languageEnglish
JournalGeneral Thoracic and Cardiovascular Surgery
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Warm Ischemia
Lung Transplantation
Allografts
Lung
Heart Arrest
Histology
Flow Cytometry
T-Lymphocytes

Keywords

  • Brain dead donor
  • Donation after cardiac death
  • Lung transplantation
  • Organ preservation
  • Rejection

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

@article{0af47dcd93384cbe9407aa160516fbb4,
title = "Prolonged warm ischemia exacerbated acute rejection after lung transplantation from donation after cardiac death in a mouse",
abstract = "Objective: In lung transplantation (LTx) from donation after cardiac death (DCD), the donor lungs are inevitably exposed to warm ischemic time (WIT) between the cardiac arrest and the initiation of cold preservation. We conducted this study to examine the effect of prolonged WIT on lung allograft rejection in a murine model of LTx from DCD. Methods: Allogeneic BALB/c → B6 LTx from DCD was performed with a WIT of 15 min (WIT15 group, n = 5) or 60 min (WIT60 group, n = 5). Recipients were immunosuppressed by perioperative costimulatory blockade. The lung allografts were analyzed by histology and flow cytometry on day 7 after the LTx. Results: Histologically, the rejection grade in the WIT60 group was significantly higher than that in the WIT15 group (3.4 ± 0.4 vs. 2.2 ± 0.2, P = 0.0278). Moreover, the intragraft CD8+ to CD4+ T cell ratio in the WIT60 group was significantly higher than that in the WIT15 group (2.3 ± 0.12 vs. 1.2 ± 0.11, P < 0.0001). Conclusions: Prolonged WIT could exacerbate the severity of lung allograft rejection after LTx from DCD. Minimization of the WIT could improve the outcomes after LTx from DCD.",
keywords = "Brain dead donor, Donation after cardiac death, Lung transplantation, Organ preservation, Rejection",
author = "Yutaka Hirano and Seiichiro Sugimoto and Sumiharu Yamamoto and Masanori Okada and Shinji Otani and Toshiaki Ohara and Masaomi Yamane and Akihiro Matsukawa and Takahiro Oto and Shinichi Toyooka",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s11748-019-01181-9",
language = "English",
journal = "General Thoracic and Cardiovascular Surgery",
issn = "1863-6705",
publisher = "Springer Japan",

}

TY - JOUR

T1 - Prolonged warm ischemia exacerbated acute rejection after lung transplantation from donation after cardiac death in a mouse

AU - Hirano, Yutaka

AU - Sugimoto, Seiichiro

AU - Yamamoto, Sumiharu

AU - Okada, Masanori

AU - Otani, Shinji

AU - Ohara, Toshiaki

AU - Yamane, Masaomi

AU - Matsukawa, Akihiro

AU - Oto, Takahiro

AU - Toyooka, Shinichi

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: In lung transplantation (LTx) from donation after cardiac death (DCD), the donor lungs are inevitably exposed to warm ischemic time (WIT) between the cardiac arrest and the initiation of cold preservation. We conducted this study to examine the effect of prolonged WIT on lung allograft rejection in a murine model of LTx from DCD. Methods: Allogeneic BALB/c → B6 LTx from DCD was performed with a WIT of 15 min (WIT15 group, n = 5) or 60 min (WIT60 group, n = 5). Recipients were immunosuppressed by perioperative costimulatory blockade. The lung allografts were analyzed by histology and flow cytometry on day 7 after the LTx. Results: Histologically, the rejection grade in the WIT60 group was significantly higher than that in the WIT15 group (3.4 ± 0.4 vs. 2.2 ± 0.2, P = 0.0278). Moreover, the intragraft CD8+ to CD4+ T cell ratio in the WIT60 group was significantly higher than that in the WIT15 group (2.3 ± 0.12 vs. 1.2 ± 0.11, P < 0.0001). Conclusions: Prolonged WIT could exacerbate the severity of lung allograft rejection after LTx from DCD. Minimization of the WIT could improve the outcomes after LTx from DCD.

AB - Objective: In lung transplantation (LTx) from donation after cardiac death (DCD), the donor lungs are inevitably exposed to warm ischemic time (WIT) between the cardiac arrest and the initiation of cold preservation. We conducted this study to examine the effect of prolonged WIT on lung allograft rejection in a murine model of LTx from DCD. Methods: Allogeneic BALB/c → B6 LTx from DCD was performed with a WIT of 15 min (WIT15 group, n = 5) or 60 min (WIT60 group, n = 5). Recipients were immunosuppressed by perioperative costimulatory blockade. The lung allografts were analyzed by histology and flow cytometry on day 7 after the LTx. Results: Histologically, the rejection grade in the WIT60 group was significantly higher than that in the WIT15 group (3.4 ± 0.4 vs. 2.2 ± 0.2, P = 0.0278). Moreover, the intragraft CD8+ to CD4+ T cell ratio in the WIT60 group was significantly higher than that in the WIT15 group (2.3 ± 0.12 vs. 1.2 ± 0.11, P < 0.0001). Conclusions: Prolonged WIT could exacerbate the severity of lung allograft rejection after LTx from DCD. Minimization of the WIT could improve the outcomes after LTx from DCD.

KW - Brain dead donor

KW - Donation after cardiac death

KW - Lung transplantation

KW - Organ preservation

KW - Rejection

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SN - 1863-6705

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