Signaling pathways involved in desflurane-induced postconditioning in human atrial myocardium in vitro

Massimo Massetti, Sandrine Lemoine, Gallic Beauchef, Lan Zhu, Emmanuelle Renard, Olivier Lepage, André Khayat, Philippe Galera, Jean Louis Gérard, Jean Luc Hanouz

Risultato della ricerca: Contributo in rivistaArticolo in rivista

19 Citazioni (Scopus)

Abstract

BACKGROUND: Isoflurane and sevoflurane have been shown to elicit myocardial postconditioning, but the effect of desflurane remain unknown. The authors studied the mechanisms involved in desflurane-induced myocardial postconditioning. METHODS: Contracting isolated human right atrial trabeculae (34 degrees C, stimulation frequency 1 Hz) were exposed to 30-min hypoxia followed by 60-min reoxygenation. Desflurane at 3%, 6%, and 9% was administered during the first 5-min of reoxygenation. Postconditioning with 6% desflurane was studied in the presence of 1 microM calphostin C, a protein kinase C inhibitor; 800 mm 5-hydroxydecanoate, a mitochondrial adenosine triphosphate-sensitive potassium channels antagonist; 1 microM Akt inhibitor; 20 microM PD89058, an extracellular-regulated kinase 1/2 inhibitor; and 1 microM SB 202190, a p38 mitogen-activated protein kinase inhibitor. The force of contraction at the end of the 60-min reoxygenation period was compared (mean +/- SD). The p38 mitogen-activated protein kinase phosphorylation was studied using Western blotting. RESULTS: Desflurane at 3% (77 +/- 10% of baseline), 6% (90 +/- 14% of baseline), and 9% (86 +/- 11% of baseline) enhanced the recovery of force after 60 min of reoxygenation as compared with the control group (51 +/- 9% of baseline; P < 0.001). Calphostin C (55 +/- 3% of baseline), 5-hydroxydecanoate (53 +/- 3% of baseline), Akt inhibitor (57 +/- 8% of baseline), PD89058 (64 +/- 6% of baseline), and SB 202190 (61 +/- 3% of baseline) abolished desflurane-induced postconditioning. Western blot analysis showed that 6% desflurane increased p38 mitogen-activated protein kinase phosphorylation. CONCLUSIONS: In vitro, desflurane postconditioned human atrial myocardium through protein kinase C activation, opening of mitochondrial adenosine triphosphate-sensitive potassium channels, Akt and extracellular-regulated kinase 1/2 activation, and p38 mitogen-activated protein kinase phosphorylation.
Lingua originaleEnglish
pagine (da-a)1036-1044
Numero di pagine9
RivistaAnesthesiology
Volume109
DOI
Stato di pubblicazionePubblicato - 2008

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Heart Atria
  • Humans
  • In Vitro Techniques
  • Ischemic Preconditioning, Myocardial
  • Isoflurane
  • Middle Aged
  • Myocardial Contraction
  • Signal Transduction
  • Ventricular Function, Left

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