aromatase inhibition attenuates desflurane-induced preconditioning against acute myocardial infarction in male mouse heart in vivo芳香化酶抑制变弱desflurane-induced预处理对急性心肌梗死在雄性老鼠体内.pdfVIP

Aromatase Inhibition Attenuates Desflurane-Induced Preconditioning against Acute Myocardial Infarction in Male Mouse Heart In Vivo 1 2 3 1 2 Virginija Jazbutyte *, Jan Stumpner , Andreas Redel , Johan M. Lorenzen , Norbert Roewer , Thomas Thum1., Franz Kehl4. 1 Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School (MHH), Hannover, Germany, 2 Department of Anesthesia and Critical ¨ ¨ Care, University of Wurzburg, Wurzburg, Germany, 3 Department of Anesthesia, University of Regensburg, Regensburg, Germany, 4 Department of Anesthesiology and Critical Care, Klinikum Karlsruhe, Karslruhe, Germany Abstract The volatile anesthetic desflurane (DES) effectively reduces cardiac infarct size following experimental ischemia/reperfusion injury in the mouse heart. We hypothesized that endogenous estrogens play a role as mediators of desflurane-induced preconditioning against myocardial infarction. In this study, we tested the hypothesis that desflurane effects local estrogen synthesis by modulating enzyme aromatase expression and activity in the mouse heart. Aromatase metabolizes testosterone to 17b- estradiol (E2) and thereby significantly contributes to local estrogen synthesis. We tested aromatase effects in acute myocardial infarction model in male mice. The animals were randomized and subjected to four groups which were pre-treated with the selective aromatase inhibitor anastrozole (A group) and DES alone (DES group) or in combination (A+DES group) for 15 minutes prior to surgical intervention whereas the control group received 0.9% NaCl (CON group). All animals were subjected to 45 minutes ischemia