Sevoflurane confers additive cardioprotection to ethanol preconditioning associated with enhanced phosphorylation of glycogen synthase kinase-3β and inhibition of mitochondrial permeability transition pore opening.

Authors

Anna Onishi, Osaka Dental UniversityFollow
Masami Miyamae, Osaka Dental UniversityFollow
Hiroshi Inoue, Osaka Dental University
Kazuhiro Kaneda, Osaka Dental UniversityFollow
Chika Okusa, Osaka Dental University
Yoshitaka Inamura, Osaka Dental UniversityFollow
Mayumi Shiomi, Osaka Dental UniversityFollow
Shizuka Koshinuma, Osaka Dental UniversityFollow
Yoshihiro Momota, Osaka Dental UniversityFollow
Vincent M. Figueredo, Einstein Medical Center and Jefferson Medical CollegeFollow

Document Type

Article

Publication Date

10-1-2013

Comments

This article has been peer reviewed. It is the authors' final version prior to publication in Journal of cardiothoracic and vascular anesthesia.

Volume 27, Issue 5, October 2013, Pages 916-24.

The published version is available at DOI: 10.1053/j.jvca.2012.10.002. Copyright © Elsevier Inc.

Abstract

OBJECTIVE: The purposes of this study were to investigate whether sevoflurane (SEVO) enhances moderate-dose ethanol (EtOH) preconditioning and whether this additional cardioprotection is associated with glycogen synthase kinase-3β (GSK-3β), protein kinase B (Akt), mammalian target of rapamycin (mTOR), 70-kDa ribosomal s6 kinase-1 (p70s6K), and/or mitochondrial permeability transition pore (MPTP) opening.

DESIGN: In vitro study using an isolated heart Langendorff preparation.

SETTING: University research laboratory.

PARTICIPANTS: Male guinea pigs (n = 170).

INTERVENTIONS: Isolated perfused guinea pig hearts underwent 30-minute ischemia and 120-minute reperfusion (control). The EtOH group received 5% EtOH in the drinking water for 8 weeks. Anesthetic preconditioning was elicited by a 10-minute exposure to 2% SEVO in EtOH (EtOH + SEVO group) or non-EtOH (SEVO group) hearts. The inhibition of GSK-3β phosphorylation and mTOR was achieved with LY294002 and rapamycin, respectively. GSK-3β, Akt, mTOR, and p70s6K expressions were determined by western blot. Calcium-induced MPTP opening was assessed in isolated calcein-loaded mitochondria.

MEASUREMENTS AND MAIN RESULTS: After ischemia-reperfusion, the EtOH, SEVO, and EtOH + SEVO groups had higher left ventricular developed pressure recovery and lower end-diastolic pressure versus the control group. Infarct size was smaller in the EtOH and SEVO groups versus control and even smaller in the EtOH + SEVO group. Phosphorylation of GSK-3β and Akt, but not mTOR and p70s6K, was increased in the EtOH and SEVO groups. Phosphorylation of GSK-3β, but not mTOR and p70s6K, was further increased in the EtOH + SEVO group. The EtOH and SEVO groups exhibited a smaller calcium-induced MPTP opening, and the EtOH + SEVO presented an even smaller MPTP opening.

CONCLUSIONS: SEVO and chronic EtOH preconditioning offer additive cardioprotection. This effect is associated with an increased GSK-3β phosphorylation and an inhibition of MPTP opening.

Recommended Citation

Onishi, Anna; Miyamae, Masami; Inoue, Hiroshi; Kaneda, Kazuhiro; Okusa, Chika; Inamura, Yoshitaka; Shiomi, Mayumi; Koshinuma, Shizuka; Momota, Yoshihiro; and Figueredo, Vincent M., "Sevoflurane confers additive cardioprotection to ethanol preconditioning associated with enhanced phosphorylation of glycogen synthase kinase-3β and inhibition of mitochondrial permeability transition pore opening." (2013). Division of Cardiology Faculty Papers. Paper 30.
https://jdc.jefferson.edu/cardiologyfp/30

PubMed ID

23266287