BACKGROUND Volatile
anesthetic preconditioning confers delayed cardioprotection against
ischemia/reperfusion injury (I/R).
AMP-activated protein kinase (AMPK) takes part in autophagy activation. Furthermore, autophagic flux is thought to be impaired after I/R. We hypothesized that delayed cardioprotection can restore autophagic flux by activating AMPK. MATERIAL AND METHODS All male rat hearts underwent 30-min
ischemia and 120-min reperfusion with or without
sevoflurane exposure.
AMPK inhibitor compound C (250 μg/kg, iv) was given at the reperfusion period. Autophagic flux blocker
chloroquine (10 mg/kg, ip) was administrated 1 h before the experiment.
Myocardial infarction,
nicotinamide adenine dinucleotide (NAD⁺) content, and
cytochrome c were measured. To evaluate autophagic flux, the markers of
microtubule-associated protein 1 light chain 3 (LC3) I and II, P62 and
Beclin 1, and lysosome-associated membrane protein-2 (LAMP 2) were analyzed. RESULTS The delayed cardioprotection enhanced post-ischemic AMPK activation, reduced
infarction, CK-MB level, NAD⁺ content loss and
cytochrome c release, and compound C blocked these effects.
Sevoflurane restored impaired autophagic flux through a lower ratio of LC3II/LC3I, downregulation of P62 and
Beclin 1, and higher expression in LAMP 2. Consistently, compound C inhibited these changes of autophagy flux. Moreover,
chloroquine pretreatment abolished
sevoflurane-induced
infarct size reduction, CK-MB level, NAD⁺ content loss, and
cytochrome c release, with concomitant increase the ratios of LC3II/LC3I and levels of P62 and
Beclin 1, but p-AMPK expression was not downregulated by
chloroquine. CONCLUSIONS
Sevoflurane exerts a delayed cardioprotective effects against myocardial injury in rats by activation of AMPK and restoration of I/R-impaired autophagic flux.