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

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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.

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Acknowledgements

This study was supported by a Grant-in-Aid for Scientific Research, Grant no. 24791461, from the Japan Society for the Promotion of Science and JSPS Fujita Memorial Fund for Medical Research.

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Authors and Affiliations

  1. Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Yutaka Hirano, Sumiharu Yamamoto, Masanori Okada, Masaomi Yamane & Shinichi Toyooka

  2. Department of General Thoracic Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Seiichiro Sugimoto

  3. Department of Organ Transplant Center, Okayama University Hospital, Okayama, Japan

    Shinji Otani & Takahiro Oto

  4. Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Toshiaki Ohara & Akihiro Matsukawa

Authors
  1. Yutaka Hirano
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  2. Seiichiro Sugimoto
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  3. Sumiharu Yamamoto
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  4. Masanori Okada
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  5. Shinji Otani
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  7. Masaomi Yamane
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  8. Akihiro Matsukawa
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  9. Takahiro Oto
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Correspondence to Seiichiro Sugimoto.

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Yutaka Hirano and his co-authors have no conflicts of interest.

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Hirano, Y., Sugimoto, S., Yamamoto, S. et al. Prolonged warm ischemia exacerbated acute rejection after lung transplantation from donation after cardiac death in a mouse. Gen Thorac Cardiovasc Surg 68, 57–62 (2020). https://doi.org/10.1007/s11748-019-01181-9

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  • DOI: https://doi.org/10.1007/s11748-019-01181-9

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