Failure to protect against myocardial ischemia-reperfusion injury with sevoflurane postconditioning in old rats in vivo.

Abstract:

BACKGROUND:Sevoflurane post-conditioning (SpostC) 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 (MEK1/2) inhibitor. Western blotting was used to determine the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2). 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 ERK1/2 (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 MEK1/2 inhibitor in young rats, respectively, but failed to activate Akt and ERK1/2 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 MEK1/2 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 ERK1/2, and resultant failure to inhibit mPTP opening.

authors

Li H,Zhou C,Chen D,Fang N,Yao Y,Li L

doi

10.1111/aas.12156

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

1024-31

issue

8

eissn

0001-5172

issn

1399-6576

journal_volume

57

pub_type

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