Activation of prosurvival signaling pathways during the memory phase of volatile anesthetic preconditioning in human myocardium: a pilot study

Mol Cell Biochem. 2014 Mar;388(1-2):195-201. doi: 10.1007/s11010-013-1910-5. Epub 2013 Nov 26.

Abstract

According to a compelling body of evidence anesthetic preconditioning (APC) attenuates the deleterious consequences of ischemia-reperfusion and protects the heart through a mechanism similar to ischemic preconditioning. The present study was purported to investigate the intracellular signaling pathways activated in human myocardium in response to a preconditioning protocol with two different volatile anesthetics, namely isoflurane and sevoflurane. To this aim, phosphorylation of PKCα and -δ, ERK1/2, Akt, and GSK3β was determined at the end of the APC protocol, in human atrial samples harvested from patients undergoing open-heart surgery. The results demonstrate that preconditioning with volatile anesthetics triggers the activation of PKCδ and -α isoforms and of prosurvival kinases, ERK1/2, and Akt, while inhibiting their downstream target GSK3β during the memory phase.

MeSH terms

  • Aged
  • Anesthetics, General / administration & dosage
  • Anesthetics, General / pharmacology*
  • Anesthetics, Inhalation / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Heart / drug effects*
  • Humans
  • Ischemic Preconditioning, Myocardial / methods*
  • Isoflurane / pharmacology
  • Male
  • Methyl Ethers / pharmacology
  • Middle Aged
  • Myocardial Ischemia / prevention & control*
  • Phosphorylation
  • Pilot Projects
  • Protein Kinase C-alpha / metabolism
  • Protein Kinase C-delta / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Sevoflurane
  • Signal Transduction / drug effects
  • Thoracic Surgery

Substances

  • Anesthetics, General
  • Anesthetics, Inhalation
  • Methyl Ethers
  • Sevoflurane
  • Isoflurane
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • PRKCA protein, human
  • Protein Kinase C-alpha
  • Protein Kinase C-delta
  • Extracellular Signal-Regulated MAP Kinases
  • Glycogen Synthase Kinase 3