Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning: role of protein kinase B/Akt signaling

Détails

ID Serval
serval:BIB_722F15D861E2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning: role of protein kinase B/Akt signaling
Périodique
Anesthesiology
Auteur(s)
Feng  J., Fischer  G., Lucchinetti  E., Zhu  M., Bestmann  L., Jegger  D., Arras  M., Pasch  T., Perriard  J. C., Schaub  M. C., Zaugg  M.
ISSN
0003-3022 (Print)
Statut éditorial
Publié
Date de publication
05/2006
Volume
104
Numéro
5
Pages
1004-14
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Résumé
BACKGROUND: Postinfarct remodeled myocardium exhibits numerous structural and biochemical alterations. So far, it is unknown whether postconditioning elicited by volatile anesthetics can also provide protection in the remodeled myocardium. METHODS: Myocardial infarct was induced in male Wistar rats by ligation of the left anterior descending coronary artery. Six weeks later, hearts were buffer-perfused and exposed to 40 min of ischemia followed by 90 min of reperfusion. Anesthetic postconditioning was induced by 15 min of 2.1 vol% isoflurane. In some experiments, LY294002 (15 microM), a phosphatidylinositol 3-kinase inhibitor, was coadministered with isoflurane. Masson's trichrome staining, immunohistochemistry, Western blot analysis, and reverse-transcription polymerase chain reaction served to confirm remodeling. In buffer-perfused hearts, functional recovery was recorded, and acute infarct size was measured using 1% triphenyltetrazolium chloride staining and lactate dehydrogenase release during reperfusion. Western blot analysis was used to determine phosphorylation of reperfusion injury salvage kinases including protein kinase B/Akt and its downstream targets after 15 min of reperfusion. RESULTS: Infarct hearts exhibited typical macroscopic and molecular changes of remodeling. Isoflurane postconditioning improved functional recovery and decreased acute infarct size, as determined by triphenyltetrazolium (35 +/- 5% in unprotected hearts vs. 8 +/- 3% in anesthetic postconditioning; P < 0.05) and lactate dehydrogenase release. This protection was abolished by LY294002, which inhibited phosphorylation of protein kinase B/Akt and its downstream targets glycogen synthase kinase 3beta, endothelial nitric oxide synthase, and p70S6 kinase. CONCLUSIONS: Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning via protein kinase B/Akt signaling. This is the first time to demonstrate that anesthetic postconditioning retains its marked protection in diseased myocardium.
Mots-clé
Anesthetics, Inhalation/*pharmacology Animals Blotting, Western *Cardiotonic Agents Hemodynamic Processes/drug effects Isoflurane/*pharmacology Male Myocardium/ultrastructure Oncogene Protein v-akt/*physiology Proto-Oncogene Proteins c-akt/*physiology RNA, Messenger/biosynthesis/isolation & purification Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction Signal Transduction/*drug effects Ventricular Remodeling/*drug effects
Pubmed
Web of science
Création de la notice
28/01/2008 10:28
Dernière modification de la notice
03/03/2018 18:16
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