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Failure to protect against myocardial ischemia‐reperfusion injury with sevoflurane postconditioning in old rats in vivo
Author(s) -
LI H.,
ZHOU C.,
CHEN D.,
FANG N.,
YAO Y.,
LI L.
Publication year - 2013
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/aas.12156
Subject(s) - medicine , sevoflurane , in vivo , ischemia , reperfusion injury , myocardial reperfusion injury , myocardial ischemia , heart failure , anesthesia , pharmacology , cardiology , microbiology and biotechnology , biology
Background Sevoflurane post‐conditioning ( S post C ) protects young hearts against ischemia‐reperfusion injury. It is unknown whether the infarct‐limiting effect is also maintained in aged cohorts and whether there are age‐associated differences in the underlying mechanisms. Methods Young or old rats were randomly subjected to 30‐min myocardial ischemia, followed by 120‐min reperfusion in vivo, with or without SpostC in the presence or absence of phosphatidylinositol 3‐kinase ( PI3K ) or mitogen‐activated protein kinase kinase 1/2 ( MEK 1/2) inhibitor. W estern blotting was used to determine the phosphorylation of protein kinase B ( Akt ) and extracellular signal‐regulated kinase 1/2 ( ERK 1/2). Myocardial nicotinamide adenine dinucleotide ( NAD + ) level was measured to indicate mitochondrial permeability transition pore ( mPTP ) opening. Results SpostC significantly decreased infarct size in young (35 ± 4% vs. 56 ± 3%, P < 0.05) but not old rats (45 ± 3% vs. 47 ± 4%, P > 0.05) compared with each control group. SpostC substantially augmented phosphorylation of Akt (0.74 ± 0.03 arbitrary units vs. 0.27 ± 0.03 arbitrary units, P < 0.05) or ERK 1/2 (0.85 ± 0.04 arbitrary units vs. 0.29 ± 0.04 arbitrary units, P < 0.05) compared with control group, which was abolished by PI3K or MEK 1/2 inhibitor in young rats, respectively, but failed to activate Akt and ERK 1/2 in old rats. NAD + level (nmol/g tissue) was higher in SpostC group in young (118.57 ± 9.27 vs. 46.78 ± 4.54, P < 0.05) but not old rats (58.50 ± 7.16 vs. 61.15 ± 5.50, P > 0.05) compared with each control group. PI3K or MEK 1/2 inhibitor abrogated the infarct‐sparing effect and inhibition of loss of NAD + induced by SpostC in young rats, respectively. Conclusion SpostC ‐mediated cardioprotection in young rats is not effective in senescent rats, which may at least be the consequence of failure to activate Akt and ERK 1/2, and resultant failure to inhibit mPTP opening.