Cardioprotection of sevoflurane postconditioning by activating extracellular signal-regulated kinase 1/2 in isolated rat hearts.
OBJECTIVE
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 micromol/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.


CONCLUSIONS
Anesthetic postconditioning by sevoflurane effectively protects against reperfusion damage by activating ERK1/2 in vitro.
Chen
Hong-tao
HT
Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, Xuzhou 221002, China.
Yang
Cheng-xiang
CX
Li
Heng
H
Zhang
Cheng-jing
CJ
Wen
Xian-jie
XJ
Zhou
Jun
J
Fan
You-ling
YL
Huang
Teng
T
Zeng
Yin-ming
YM
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D006334:Heart Function Tests; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D002316:Cardiotonic Agents; D008738:Methyl Ethers; D000077149:Sevoflurane; D045304:Cytochromes c; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3