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

ABSTRACT

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 GSK3ß 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 GSK3ß 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.