Signaling pathways involved in desflurane-induced postconditioning in human atrial myocardium in vitro.
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.
Lemoine
Sandrine
S
Laboratory of Experimental Anesthesiology and Cellular Physiology, Department of Cardiac and Thoracic Surgery, Centre Hospitalier Universitaire Caen, France.
Beauchef
Gallic
G
Zhu
Lan
L
Renard
Emmanuelle
E
Lepage
Olivier
O
Massetti
Massimo
M
Khayat
André
A
Galera
Philippe
P
Gérard
Jean-Louis
JL
Hanouz
Jean-Luc
JL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077335:Desflurane; D006325:Heart Atria / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D000077335:Desflurane; D007530:Isoflurane