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Sevoflurane postconditioning prevents activation of caspase 3 and 9 through antiapoptotic signaling after myocardial ischemia–reperfusion

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Abstract

Purpose

Volatile anesthetic postconditioning reduces apoptosis through antiapoptotic signaling. Whether sevoflurane postconditioning prevents activation of caspase 9 and 3, which are implicated in the initiation and execution step of apoptosis, is not known.

Methods

Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion [control (CTL)]. Anesthetic postconditioning was elicited with sevoflurane (2%) for 2 min at reperfusion onset (POST). LY294002, phosphatidylinositol-3-kinase (PI3K)/Akt (protein kinase B) inhibitor; and PD98059, extracellular signal-regulated kinase 1/2 (ERK) inhibitor, were administered for 10 min before ischemia and throughout the reperfusion period in POST (POST + LY, POST + PD). Left-ventricular-developed (LVDP) and LV end-diastolic (LVEDP) pressures and infarct size were measured. Western blot analysis determined phosphorylated Akt and ERK expression. Myocardial caspase 3 and 9 were determined immunohistochemically.

Results

After ischemia–reperfusion, POST had higher LVDP (57 ± 9 vs. 38 ± 7 mmHg, p < 0.05) and lower LVEDP (21 ± 8 vs. 46 ± 15 mmHg, p < 0.05) versus CTL. Infarct size was significantly reduced in POST versus CTL (15 ± 3 vs. 41 ± 11%, p < 0.001). Phosphorylation of Akt and ERK after reperfusion was significantly increased in POST versus CTL. Immunoreactivity for caspase 3 and 9 was greater in the nucleus of myocytes and endothelial cells in CTL. POST attenuated this increased immunoreactivity. LY294002 and PD98059 abolished the effect of POST on caspase 3 and 9 immunoreactivity.

Conclusions

Sevoflurane postconditioning prevents activation of caspase 3 and 9, mediators of apoptosis in ischemia–reperfusion injury. This caspase activation is mediated by phosphorylation of Akt and ERK.

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Acknowledgments

We thank Dr. Vincent M. Figueredo for careful review of this manuscript and Dr. Masahiro Wato for his kind advice and help. This study was conducted at the Laboratory Animal Facilities and Dental Bioscience I, Institute of Dental Research, Osaka Dental University, and was supported by Osaka Dental University Research Funds (08-06) (Yoshitaka Inamura) and Grant-in-Aid for Scientific Research (C) 20592382 (Masami Miyamae), “High-Tech Research Center” Project for Private Universities: matching fund subsidy, 2007–2011 from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Naochika Domae).

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Authors and Affiliations

  1. Graduate School, Dentistry (Department of Anesthesiology), Osaka Dental University, Osaka, Japan

    Yoshitaka Inamura

  2. Department of Internal Medicine, Osaka Dental University, 8-1 Kuzuha Hanazono-cho, Hirakata, Osaka, 573-1121, Japan

    Masami Miyamae & Naochika Domae

  3. Department of Anesthesiology, Osaka Dental University, Osaka, Japan

    Shingo Sugioka & Junichiro Kotani

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  1. Yoshitaka Inamura
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  2. Masami Miyamae
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  5. Junichiro Kotani
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Correspondence to Masami Miyamae.

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Inamura, Y., Miyamae, M., Sugioka, S. et al. Sevoflurane postconditioning prevents activation of caspase 3 and 9 through antiapoptotic signaling after myocardial ischemia–reperfusion. J Anesth 24, 215–224 (2010). https://doi.org/10.1007/s00540-010-0877-6

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  • DOI: https://doi.org/10.1007/s00540-010-0877-6

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