Protective Effect of Sevoflurane Postconditioning against Cardiac Ischemia/Reperfusion Injury via Ameliorating Mitochondrial Impairment, Oxidative Stress and Rescuing Autophagic Clearance.
OBJECTIVE
Myocardial infarction leads to heart failure. Autophagy is excessively activated in myocardial ischemia/reperfusion (I/R) in rats. The aim of this study is to investigate whether the protection of sevoflurane postconditioning (SPC) in myocardial I/R is through restored impaired autophagic flux.


METHODS
Except for the sham control (SHAM) group, each rat underwent 30 min occlusion of the left anterior descending coronary (LAD) followed by 2 h reperfusion. Cardiac infarction was determined by 2,3,5-triphenyltetrazolium chloride triazole (TTC) staining. Cardiac function was examined by hemodynamics and echocardiography. The activation of autophagy was evaluated by autophagosome accumulation, LC3 conversion and p62 degradation. Potential molecular mechanisms were investigated by immunoblotting, real-time PCR and immunofluorescence staining.


RESULTS
SPC improved the hemodynamic parameters, cardiac dysfunction, histopathological and ultrastructural damages, and decreased myocardial infarction size after myocardial I/R injury (P < 0.05 vs. I/R group). Compared with the cases in I/R group, myocardial ATP and NAD+ content, mitochondrial function related genes and proteins, and the expressions of SOD2 and HO-1 were increased, while the expressions of ROS and Vimentin were decreased in the SPC group (P < 0.05 vs. I/R group). SPC significantly activated Akt/mTOR signaling, and inhibited the formation of Vps34/Beclin1 complex via increasing expression of Bcl2 protein (P < 0.05 vs. I/R group). SPC suppressed elevated expressions of LC3 II/I ratio, Beclin1, Atg5 and Atg7 in I/R rat, which indicated that SPC inhibited over-activation of autophagy, and promoted autophagosome clearance. Meanwhile, SPC significantly suppressed the decline of Opa1 and increases of Drp1 and Parkin induced by I/R injury (P < 0.05 vs. I/R group). Moreover, SPC maintained the contents of ATP by reducing impaired mitochondria.


CONCLUSIONS
SPC protects rat hearts against I/R injury via ameliorating mitochondrial impairment, oxidative stress and rescuing autophagic clearance.
Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Peng
P
Yu
Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Jing
J
Zhang
Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Shuchun
S
Yu
Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Zhenzhong
Z
Luo
Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Fuzhou
F
Hua
Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Linhui
L
Yuan
Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Zhidong
Z
Zhou
Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Qin
Q
Liu
Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Xiaohong
X
Du
Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Sisi
S
Chen
Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Lieliang
L
Zhang
Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, China.
Guohai
G
Xu
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D002316:Cardiotonic Agents / Q000494:pharmacology*; D058546:Class III Phosphatidylinositol 3-Kinases / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D066263:Protein Aggregation, Pathological; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D000077149:Sevoflurane; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016276:Ventricular Function / Q000187:drug effects
D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; D002316:Cardiotonic Agents; D008738:Methyl Ethers; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000077149:Sevoflurane; D000255:Adenosine Triphosphate; D058546:Class III Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases