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Dexmedetomidine Maintains Its Direct Cardioprotective Effect Against Ischemia/Reperfusion Injury in Hypertensive Hypertrophied Myocardium

Yoshikawa, Yusuke MD; Hirata, Naoyuki MD, PhD; Kawaguchi, Ryoichi MD, PhD; Tokinaga, Yasuyuki MD, PhD; Yamakage, Michiaki MD, PhD
doi: 10.1213/ANE.0000000000002452
Research Report: PDF Only

BACKGROUND:

Dexmedetomidine (DEX) has a direct cardioprotective effect against ischemia/reperfusion injury through endothelial nitric oxide synthase (eNOS) phosphorylation via α2-adrenoreceptor (α2-AR). By using spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat models, the cardioprotective effect of DEX in hypertrophied myocardium and the differential characteristics of cardiac α2-AR and the I1 imidazoline receptor (I1R) were examined.

METHODS:

Langendorff-perfused rat hearts underwent 40 minutes of global ischemia followed by 120 minutes of reperfusion in the presence or absence of DEX before ischemia. Infarct size was measured, and eNOS phosphorylation was assessed by Western blotting. The presence and expression of the receptors were assessed by immunohistochemistry, real-time reverse transcriptase polymerase chain reaction, and Western blotting.

RESULTS:

In WKY, DEX significantly decreased infarct size and increased phosphorylated-eNOS/eNOS. These effects were counteracted by yohimbine (α2-AR antagonist) and efaroxan (α2-AR and I1R antagonist). In SHR, DEX significantly decreased infarct size, and the effect was counteracted by efaroxan but not yohimbine. DEX did not alter phosphorylated-eNOS/eNOS in SHR. α2-AR and I1R were observed in WKY and SHR hearts. Although alpha2A-AR and alpha2B-AR messenger RNA and protein levels were upregulated in SHR, I1R expression was comparable between the 2 species.

CONCLUSIONS:

In the hypertrophied heart, DEX maintains its direct cardioprotective effect against ischemia/reperfusion injury via I1R in an eNOS-nondependent manner despite upregulation of α2-AR.

Accepted for publication July 24, 2017.

Funding: This report was partially supported by a Grant-in-Aid for Young Scientists (B) (Research No. 26861237) from the Japan Society for the Promotion of Science, Tokyo, Japan (to Y.Y.).

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.anesthesia-analgesia.org).

Reprints will not be available from the authors.

Address correspondence to Yusuke Yoshikawa, MD, Department of Anesthesiology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, Hokkaido 8543, Japan. Address e-mail to y.yoshikawa@sapmed.ac.jp.

© 2017 International Anesthesia Research Society

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