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Sevoflurane has postconditioning as well as preconditioning properties against hepatic warm ischemia–reperfusion injury in rats

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Abstract

Purpose

Ischemia–reperfusion (IR) injury is inevitable after liver transplantation and liver resection with inflow occlusion. Sevoflurane has been widely used during hepatobiliary surgery and was reported to exhibit preconditioning (PreC) properties against hepatic IR injury; however, its postconditioning (PostC) properties remain unknown. This study examined whether a clinically applicable dose of sevoflurane has PostC and PreC properties against hepatic IR injury and roles of heme oxygenase-1 (HO-1).

Methods

Warm ischemia was induced in male Wistar rats, excluding the sham group, for 1 h, followed by 3 h of reperfusion. Group C received propofol from 60 min before ischemia until the end of the experimental procedure. In the SPreC and SPostC groups, propofol was replaced by 2.5% sevoflurane for 30 min from 35 min before ischemia in the SPreC group and for 30 min from 5 min before reperfusion in the SPostC group. The SPreC+Z and SPostC+Z groups received a HO-1 inhibitor, zinc protoporphyrin (Znpp), 60 min before ischemia, and sevoflurane PreC and PostC were induced.

Results

Serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels, and histological damage scores in the SPreC and SPostC groups were significantly lower than those in group C. Inhibiting HO-1 with Znpp partially blocked these protective effects of sevoflurane. Sevoflurane PreC and PostC significantly increased the number of HO-1-positive Kupffer cells in comparison with group C, and Znpp prevented sevoflurane-induced HO-1 expression.

Conclusion

PostC and PreC by sevoflurane at a clinically applicable dose have equally protective effects against hepatic IR injury by increasing HO-1 expression.

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Acknowledgements

The authors are grateful to Dr. Katsuya Matsuda (Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan) and Dr. Suntaro Sato (Clinical Research Center, Nagasaki University Hospital, Nagasaki, Japan) for their useful suggestions for histopathology and immunohistology examinations, and statistical analysis.

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Authors and Affiliations

  1. Department of Anesthesiology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Saki Shiraishi, Taiga Ichinomiya & Tetsuya Hara

  2. Department of Anesthesiology, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan

    Sungsam Cho

  3. Department of Anesthesiology, Nagasaki University Hospital, Nagasaki, Japan

    Daiji Akiyama, Itsuko Shibata, Osamu Yoshitomi & Takuji Maekawa

  4. Department of Gastroenterology, Nagasaki University Hospital, Nagasaki, Japan

    Eisuke Ozawa & Hisamitsu Miyaaki

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  1. Saki Shiraishi
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Correspondence to Saki Shiraishi.

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Shiraishi, S., Cho, S., Akiyama, D. et al. Sevoflurane has postconditioning as well as preconditioning properties against hepatic warm ischemia–reperfusion injury in rats. J Anesth 33, 390–398 (2019). https://doi.org/10.1007/s00540-019-02642-4

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  • DOI: https://doi.org/10.1007/s00540-019-02642-4

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