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

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°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 μm calphostin C, a protein kinase C inhibitor; 800 mm 5-hydroxydecanoate, a mitochondrial adenosine triphosphate-sensitive potassium channels antagonist; 1 μm Akt inhibitor; 20 μm PD89058, an extracellular-regulated kinase 1/2 inhibitor; and 1 μm 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. © 2008, the American Society of Anesthesiologists, Inc.