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
Institution
Titre
Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning: role of protein kinase B/Akt signaling
Périodique
Anesthesiology
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
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
20/08/2019 15:30