Induction of autophagy restores the loss of sevoflurane cardiac preconditioning seen with prolonged ischemic insult.

Authors

Mayumi Shiomi, Osaka Medical CollegeFollow
Masami Miyamae, Osaka Dental UniversityFollow
Genzou Takemura, Gifu University Graduate School of MedicineFollow
Kazuhiro Kaneda, Osaka Dental UniversityFollow
Yoshitaka Inamura, Osaka Dental UniversityFollow
Anna Onishi, Osaka Dental UniversityFollow
Shizuka Koshinuma, Osaka Dental UniversityFollow
Yoshihiro Momota, Osaka Dental UniversityFollow
Toshiaki Minami, Osaka Medical CollegeFollow
Vincent M. Figueredo, M.D., Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

2-5-2014

Comments

This article has been peer reviewed. It is the authors' final version prior to publication in European Journal of Pharmacology, Volume 724, Issue 1, February 2014, Pages 58-66.

The published version is available at DOI: 10.1016/j.ejphar.2013.12.027. Copyright © Elsevier

Abstract

Sevoflurane preconditioning against myocardial ischemia-reperfusion injury is lost if the ischemic insult is too long. Emerging evidence suggests that induction of autophagy may also confer cardioprotection against ischemia-reperfusion injury. We examined whether induction of autophagy prolongs sevoflurane preconditioning protection during a longer ischemic insult. Isolated guinea pigs hearts were subjected to 30 or 45 min ischemia, followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2% sevoflurane for 10 min prior to ischemia (SEVO-30, SEVO-45). Chloramphenicol (autophagy upregulator, 300 µM) was administered starting 20 min before ischemia and throughout reperfusion in SEVO-45 (SEVO-45+CAP). To inhibit autophagy, 3-methyladenine (10 μM) was administered during sevoflurane administration in SEVO-45+CAP. Infarct size was determined by triphenyltetrazolium chloride stain. Tissue samples were obtained before ischemia to determine autophagy-related protein (microtubule-associated protein light chain I and II: LC3-I, II), Akt and glycogen synthase kinase 3β (GSK3β) expression using Western blot analysis. The effect of autophagy on calcium-induced mitochondrial permeability transition pore (MPTP) opening in isolated calcein-loaded mitochondria was assessed. Electron microscopy was used to detect autophagosomes. Infarct size was significantly reduced in SEVO-30, but not in SEVO-45. Chloramphenicol restored sevoflurane preconditioning lost by 45 min ischemia. There were more abundant autophagozomes and LC3-II expression was significantly increased in SEVO-45+CAP. Induction of autophagy before ischemia enhanced GSK3β phosphorylation and inhibition of calcium-induced MPTP opening. These effects were abolished by 3-methyladenine. Pre-ischemic induction of autophagy restores sevoflurane preconditioning lost by longer ischemic insult. This effect is associated with enhanced inhibition of MPTP by autophagy.

Recommended Citation

Shiomi, Mayumi; Miyamae, Masami; Takemura, Genzou; Kaneda, Kazuhiro; Inamura, Yoshitaka; Onishi, Anna; Koshinuma, Shizuka; Momota, Yoshihiro; Minami, Toshiaki; and Figueredo, M.D., Vincent M., "Induction of autophagy restores the loss of sevoflurane cardiac preconditioning seen with prolonged ischemic insult." (2014). Division of Cardiology Faculty Papers. Paper 58.
https://jdc.jefferson.edu/cardiologyfp/58

PubMed ID

24374197