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-mediated cardioprotection, and their precise underlying mechanisms of action, remain incompletely understood. Methods and Results Sevoflurane preconditioning (SF-PreCon, consisting of 3 cycles of 15 minute-exposures to 2% sevoflurane prior to 30 minutes of MI) decreased MI/R injury in WT mice (caspase-3 activity −29.1%, infarct size −20.2%, and LVEDP −33.8%). In cardiac-specific AMPKα2 dominant negative overexpression (AMPK-DN) mice, the cardioprotective effect of SF-PreCon was largely retained (caspase-3 activity −26.7%, infarct size −16.7%, and LVEDP −25.9%, P<0.01). In contrast, SF-PreCon failed to significantly protect Cav3-knockout (Cav3-KO) mice against MI/R injury (P>0.05). SF-PreCon significantly decreased MI/R-induced superoxide generation in WT (−43.6%) and AMPK-DN mice (−35.5%, P<0.01), but not in Cav3-KO mice. SF-PreCon did not affect NADPH oxidase expression, but significantly inhibited COX-2 expression in WT (−38.7%) and AMPK-DN mice (−35.8%), but not in Cav-3KO mice. Conclusions We demonstrate for the first time sevoflurane preconditioning mediates cardioprotection against MI/R injury via Cav-3 dependent-COX-2 inhibition and anti-oxidative effects.

Propofol Through Upregulating Caveolin-3 Attenuates Post-Hypoxic Mitochondrial Damage and Cell Death in H9C2 Cardiomyocytes During Hyperglycemia

“…Within these microdomains, caveolins (Cav) are structural proteins of caveolae [12, 13], which interact with numerous signaling molecules (such as eNOS, PI3K, and MER/MRK etc.) that are required in cardiac protection initiated by a variety of cardioprotective interventions (e.g., ischemic preconditioning [14] and anesthetic preconditioning [15]). Cardiac I/R tolerance parallels the expression of Cav-3, the cardiac-specific isoform of Cav.…”

Abnormal Downregulation of Caveolin-3 Mediates the Pro-Fibrotic Action of MicroRNA-22 in a Model of Myocardial Infarction

“…Furthermore, its dysregulation is involved in the development of arrhythmia, myocardial hypertrophy, and myocardial ischemia/reperfusion injury [17-19]. However, no previous studies elucidated the regulatory role of Cav3 during the development of cardiac fibrosis.…”

“…Cav3 is involved in signal transduction both inside and outside of the myocardial cell membrane, and its defects are closely associated with heart disease development. Previous studies reported that Cav3 contributes to a variety of cardiac pathophysiological processes such as arrhythmogenesis, myocardial hypertrophy, and myocardial ischemia/reperfusion injury [17-19]. Cav3 was shown to be associated with protein kinase C (PKC) signaling, known to induce fibrogenesis [20-22].…”

Sevoflurane downregulates interleukin-6 and interleukin-8 levels in patients after cardiopulmonary bypass surgery: a meta-analysis

“…Inhaled anesthetics (including sevoflurane) reduce myocardial injury and the need for inotropic support in cardiac patients (Zhao et al, 2013). Our meta-analysis explored the role of inflammatory cytokines, IL-6 and IL-8, in groups pretreated and post-treated with sevoflurane.…”