Abstract
Aim:
The activation of extracellular signal-regulated kinase (ERK)1/2 protects against ischemic–reperfusion injury. Whether ERK1/2 mediates the cardioprotection of sevoflurane postconditioning is unknown. We tested whether sevoflurane postconditioning produces cardioprotection via an ERK1/2-dependent mechanism.
Methods:
In protocol 1, Langendorff-perfused Sprague–Dawley rat hearts (n=84, 12 per group), with the exception of the Sham group, were subjected to 30 min ischemia followed by 90 min reperfusion and were assigned to the untreated (control) group, followed by 4 cycles of ischemic postconditioning (25 s of each), 3% (v/v) sevoflurane postconditioning (for 5 min and 10 min of washout), and the PD98059 solvent DMSO (<0.2%), ERK1/2 inhibitor PD98059 (20 μmol/L), and Sevo+PD administration. Left ventricular hemodynamics and coronary flow at 30 min of equilibrium were recorded at 30, 60, and 90 min of reperfusion, respectively. Acute infarct size was measured by triphenyltetrazolium chloride staining. The configuration of mitochondria was observed by an electron microscope. Western blot analysis was used to determine the contents of cytosolic and mitochondrial cytochrome c at the end of reperfusion. In protocol 2, after 15 min of reperfusion, the expression of total and phosphorylated forms of ERK1/2 and its downstream target p70S6K was determined by Western blotting.
Results:
No differences in baseline hemodynamics were observed among the experimental groups (P>0.05). After reperfusion, compared with the control group, sevoflurane postconditioning and ischemic postconditioning significantly (P<0.05) improved functional recovery and largely (P<0.05) decreased myocardial infarct size (22.9%±4.6% and 21.2%±3.8%, vs 39.4%±5.7%, both P<0.05). Sevoflurane-mediated protection was abolished by PD98059.
Conclusion:
Anesthetic postconditioning by sevoflurane effectively protects against reperfusion damage by activating ERK1/2 in vitro.
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Project supported by the Open Project of the Health Department of Jiangsu Province, China (No WK2006 03).
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Chen, Ht., Yang, Cx., Li, H. et al. Cardioprotection of sevoflurane postconditioning by activating extracellular signal-regulated kinase 1/2 in isolated rat hearts. Acta Pharmacol Sin 29, 931–941 (2008). https://doi.org/10.1111/j.1745-7254.2008.00824.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00824.x
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