Sevoflurane preconditioning attenuates myocardial ischemia/reperfusion injury via caveolin-3-dependent cyclooxygenase-2 inhibition.

Abstract

BACKGROUND:

The inhaled anesthetic sevoflurane has been demonstrated to protect against myocardial ischemia/reperfusion (MI/R) injury via mechanisms involving AMP-activated protein kinase (AMPK) and caveolin-3 (Cav-3). However, the relative contributions of AMPK and Cav-3 to sevoflurane preconditioning (SF-PreCon)-mediated cardioprotection and their precise underlying mechanisms of action remain incompletely understood.

METHODS AND RESULTS:

SF-PreCon (consisting of 3 cycles of 15-minute exposure to 2% sevoflurane before 30 minutes of MI) decreased MI/R injury in wild-type mice (caspase-3 activity, -29.1%; infarct size, -20.2%; and left ventricular end diastolic pressure, -33.8%). In cardiac-specific AMPKα2 dominant-negative overexpressing mice, the cardioprotective effect of SF-PreCon was largely retained (caspase-3 activity, -26.7%; infarct size, -16.7%; and left ventricular end-diastolic pressure, -25.9%; P<0.01). In contrast, SF-PreCon failed to significantly protect Cav-3 knockout mice against MI/R injury (P>0.05). SF-PreCon significantly decreased MI/R-induced superoxide generation in wild-type (-43.6%) and AMPK dominant-negative overexpressing mice (-35.5%; P<0.01) but not in Cav-3 knockout mice. SF-PreCon did not affect nicotinamide adenine dinucleotide phosphate oxidase expression but significantly inhibited cyclooxygenase-2 expression in wild-type (-38.7%) and AMPK dominant-negative overexpressing mice (-35.8%) but not in Cav-3 knockout mice.

CONCLUSIONS:

We demonstrate for the first time SF-PreCon mediates cardioprotection against MI/R injury via caveolin-3-dependent cyclooxygenase-2 inhibition and antioxidative effects.

• Authors: Jianli Zhao, Feng Wang, Yanqing Zhang, Liyuan Jiao, Wayne Bond Lau, Lili Wang, Baojiang Liu, Erhe Gao, Walter J Koch, Xin-Liang Ma, Yajing Wang
• Journal: Circulation (Circulation) Vol. 128 Issue 11 Suppl 1 Pg. S121-9 (Sep 10 2013) ISSN: 1524-4539 [Electronic] United States
• PMID: 24030395 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Inhalation
• Caveolin 3
• Cyclooxygenase 2 Inhibitors
• Methyl Ethers
• Sevoflurane

Topics

• Anesthetics, Inhalation (therapeutic use)
• Animals
• Caveolin 3 (deficiency, genetics, physiology)
• Cells, Cultured
• Cyclooxygenase 2 Inhibitors (therapeutic use)
• Ischemic Preconditioning, Myocardial (methods)
• Male
• Methyl Ethers (therapeutic use)
• Mice
• Mice, Knockout
• Myocardial Reperfusion Injury (drug therapy, genetics, metabolism)
• Sevoflurane