Abstract
Background: Volatile anesthetic preconditioning (APC) protects against myocardial ischemia-reperfusion (IR) injury, but the precise mechanisms underlying this phenomenon remain undefined. To investigate the molecular mechanism of APC in myocardial protection, the activation of nuclear factor (NF) κB and its regulated inflammatory mediators expression were examined in the current study. Methods: Hearts from male rats were isolated, Langendorff perfused, and randomly assigned to one of three groups: (1) the control group: hearts were continuously perfused for 130 min; (2) the IR group: 30 min of equilibration, 15 min of baseline, 25 min of ischemia, 60 min of reperfusion; and (3) the APC + IR group: 30 min of equilibration, 10 min of sevoflurane exposure and a 5-min washout, 25 min of global ischemia, 60 min of reperfusion. Tissue samples were acquired at the end of reperfusion. NF-κB activity was determined by electrophoretic mobility shift assay. The NF-κB inhibitor, IκB-α, was determined by Western blot analysis. Myocardial inflammatory mediators, including tumor necrosis factor α, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase, were also assessed by Western blot analysis. Results: Nuclear factor κB-DNA binding activity was significantly increased at the end of reperfusion in rat myocardium, and cytosolic IκB-α was decreased. Supershift assay revealed the involvement of NF-κB p65 and p50 subunits. APC with sevoflurane attenuated NF-κB activation and reduced the expression of tumor necrosis factor α, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase. APC also reduced infarct size and creatine kinase release and improved myocardial left ventricular developed pressure during IR. Conclusions: The results of this study indicate that attenuation of NF-κB activation and subsequent down-regulation of NF-κB-dependent inflammatory gene expression plays an important role in the protective mechanism of APC against acute myocardial IR injury.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 540-546 |
| Number of pages | 7 |
| Journal | Anesthesiology |
| Volume | 100 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2004 |
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ASJC Scopus subject areas
- Anesthesiology and Pain Medicine
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Nuclear Factor κB and Anesthetic Preconditioning during Myocardial Ischemia-Reperfusion. / Zhong, Caiyun; Zhou, Yamei; Liu, Hong.
In: Anesthesiology, Vol. 100, No. 3, 03.2004, p. 540-546.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nuclear Factor κB and Anesthetic Preconditioning during Myocardial Ischemia-Reperfusion
AU - Zhong, Caiyun
AU - Zhou, Yamei
AU - Liu, Hong
PY - 2004/3
Y1 - 2004/3
N2 - Background: Volatile anesthetic preconditioning (APC) protects against myocardial ischemia-reperfusion (IR) injury, but the precise mechanisms underlying this phenomenon remain undefined. To investigate the molecular mechanism of APC in myocardial protection, the activation of nuclear factor (NF) κB and its regulated inflammatory mediators expression were examined in the current study. Methods: Hearts from male rats were isolated, Langendorff perfused, and randomly assigned to one of three groups: (1) the control group: hearts were continuously perfused for 130 min; (2) the IR group: 30 min of equilibration, 15 min of baseline, 25 min of ischemia, 60 min of reperfusion; and (3) the APC + IR group: 30 min of equilibration, 10 min of sevoflurane exposure and a 5-min washout, 25 min of global ischemia, 60 min of reperfusion. Tissue samples were acquired at the end of reperfusion. NF-κB activity was determined by electrophoretic mobility shift assay. The NF-κB inhibitor, IκB-α, was determined by Western blot analysis. Myocardial inflammatory mediators, including tumor necrosis factor α, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase, were also assessed by Western blot analysis. Results: Nuclear factor κB-DNA binding activity was significantly increased at the end of reperfusion in rat myocardium, and cytosolic IκB-α was decreased. Supershift assay revealed the involvement of NF-κB p65 and p50 subunits. APC with sevoflurane attenuated NF-κB activation and reduced the expression of tumor necrosis factor α, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase. APC also reduced infarct size and creatine kinase release and improved myocardial left ventricular developed pressure during IR. Conclusions: The results of this study indicate that attenuation of NF-κB activation and subsequent down-regulation of NF-κB-dependent inflammatory gene expression plays an important role in the protective mechanism of APC against acute myocardial IR injury.
AB - Background: Volatile anesthetic preconditioning (APC) protects against myocardial ischemia-reperfusion (IR) injury, but the precise mechanisms underlying this phenomenon remain undefined. To investigate the molecular mechanism of APC in myocardial protection, the activation of nuclear factor (NF) κB and its regulated inflammatory mediators expression were examined in the current study. Methods: Hearts from male rats were isolated, Langendorff perfused, and randomly assigned to one of three groups: (1) the control group: hearts were continuously perfused for 130 min; (2) the IR group: 30 min of equilibration, 15 min of baseline, 25 min of ischemia, 60 min of reperfusion; and (3) the APC + IR group: 30 min of equilibration, 10 min of sevoflurane exposure and a 5-min washout, 25 min of global ischemia, 60 min of reperfusion. Tissue samples were acquired at the end of reperfusion. NF-κB activity was determined by electrophoretic mobility shift assay. The NF-κB inhibitor, IκB-α, was determined by Western blot analysis. Myocardial inflammatory mediators, including tumor necrosis factor α, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase, were also assessed by Western blot analysis. Results: Nuclear factor κB-DNA binding activity was significantly increased at the end of reperfusion in rat myocardium, and cytosolic IκB-α was decreased. Supershift assay revealed the involvement of NF-κB p65 and p50 subunits. APC with sevoflurane attenuated NF-κB activation and reduced the expression of tumor necrosis factor α, interleukin 1, intercellular adhesion molecule 1, and inducible nitric oxide synthase. APC also reduced infarct size and creatine kinase release and improved myocardial left ventricular developed pressure during IR. Conclusions: The results of this study indicate that attenuation of NF-κB activation and subsequent down-regulation of NF-κB-dependent inflammatory gene expression plays an important role in the protective mechanism of APC against acute myocardial IR injury.
UR - http://www.scopus.com/inward/record.url?scp=1442308454&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1442308454&partnerID=8YFLogxK
U2 - 10.1097/00000542-200403000-00012
DO - 10.1097/00000542-200403000-00012
M3 - Article
C2 - 15108966
AN - SCOPUS:1442308454
VL - 100
SP - 540
EP - 546
JO - Anesthesiology
JF - Anesthesiology
SN - 0003-3022
IS - 3
ER -