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Isoflurane-induced post-conditioning in senescent hearts is attenuated by failure to activate reperfusion injury salvage kinase pathway

Chang, DJ; Chang, CH; Kim, JS; Hong, YW; Lee, WK; Shim, YH
Acta anaesthesiologica Scandinavica, 56(7):896-903, 2012
Journal Title
Acta anaesthesiologica Scandinavica
BACKGROUND: We investigated the cardioprotective effects of isoflurane administered at the onset of reperfusion in senescent rat in vivo, and the activation of the reperfusion injury salvage kinase (RISK) pathway to address a possible mechanism underlying age-related differences.

METHODS: Male Wistar rats were assigned to age groups (young, 3-5 months; old, 20-24 months), and randomly selected to receive isoflurane (1 minimum alveolar concentration) or not for 3 min before and 2 min after reperfusion (ISO postC). Rats were subjected to coronary occlusion for 30 min followed by 2 h of reperfusion. Western blot analysis was used to assess the phosphorylation of extracellular signal-regulated kinase (ERK1/2), Akt, and GSK3β 15 min after reperfusion.

RESULTS: Brief administration of isoflurane 3 min before and 2 min after the initiation of early reperfusion reduced infarct size (56 ± 8% of left ventricular area at risk, mean ± standard deviation) compared with controls (68 ± 4%) in young rats, but had no effect in old rats (56 ± 8% in ISO postC and 56 ± 10% in control, respectively). Phosphorylation of ERK1/2, Akt, and GSK3β were increased in the young ISO postC group but not in the old ISO postC group compared with control groups of the respective ages.

CONCLUSIONS: We demonstrated that isoflurane post-conditions the heart in young but not in senescent rats. Failure to activate RISK pathway may contribute to attenuation of isoflurane-induced post-conditioning effect in senescent rats.
MeSH terms
Aging/*physiologyAnimalsCardiotonic Agents/pharmacology/*therapeutic useDrug Evaluation, PreclinicalGlycogen Synthase Kinase 3/*physiologyIschemic Postconditioning/*methodsIsoflurane/pharmacology/*therapeutic use*MAP Kinase Signaling SystemMaleMitogen-Activated Protein Kinase 1/*physiologyMitogen-Activated Protein Kinase 3/*physiologyMyocardial Infarction/pathologyMyocardial ReperfusionMyocardial Reperfusion Injury/enzymology/physiopathology/*prevention & controlPhosphorylationProtein Processing, Post-TranslationalProto-Oncogene Proteins c-akt/*physiologyRandom AllocationRatsRats, Wistar
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Anesthesiology & Pain Medicine
AJOU Authors
김, 진수홍, 용우
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