Aim: To investigate the role of extracellular signal-regulated kinases (ERKs) in sevoflurane post-conditioning induced cardioprotection in vitro. Methods: Isolated rat hearts were subjected to 30 min ischemia followed by 120 min reperfusion (I/R). Sevoflurane post-conditioning was carried out by administration of O 2 -enriched gas mixture with 3% sevoflurane (SEVO) for 15 min from the onset of reperfusion. Cardiac functions, myocardial infarct size, myocardial ATP and NAD + contents, mitochondrial ultrastructure, and anti-apototic and antioncosis protein levels were measured. Results: Sevoflurane post-conditioning significantly improved the heart function, decreased infarct size and mitochondria damage, and increased myocardial ATP and NAD + content in the I/R hearts. Furthermore, sevoflurane post-conditioning significantly increased the levels of p-ERK and p-p70S6K, decreased the levels of porimin, caspase-8, cleaved caspase-3, and cytosolic cytochrome c in the I/R hearts. Co-administration of the ERK1/2 inhibitor PD98059 (20 μmol/L) abolished the sevoflurane-induced protective effects against myocardial I/R. Conclusion: Sevoflurane post-conditioning protects isolated rat hearts against myocardial I/R injury and inhibits cell oncosis and apoptosis via activation of the ERK1/2 pathway.
This study aimed to determine the role of mitochondrial adenosine
triphosphate-sensitive potassium (mitoKATP) channels and protein kinase C
(PKC)-ε in the delayed protective effects of sevoflurane preconditioning using
Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts
were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5%
sevoflurane (the second window of protection group, SWOP group) or 33% oxygen
inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and
the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane
for 60 min, respectively, without coronary occlusion. The mitoKATP channel
inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane
preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum
cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated
PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε
expression was upregulated, caspase-8 expression was downregulated, cTnI
concentrations were decreased, and the infarcts were significantly smaller
(P<0.05) in the SWOP group compared with the I/R group. Cardiac function was
worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated,
cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group
(P<0.05) compared with the SWOP group. The results suggest that
mitoKATP channels are involved in the myocardial protective effects of
sevoflurane in preconditioning against I/R injury, by regulating PKC-ε
phosphorylation before ischemia, and by downregulating caspase-8 during
reperfusion.
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