TY  - JOUR
A1  - Lotz, Christopher
A1  - Herrmann, Johannes
A1  - Notz, Quirin
A1  - Meybohm, Patrick
A1  - Kehl, Franz
T1  - Mitochondria and pharmacologic cardiac conditioning — At the heart of ischemic injury
JF  - International Journal of Molecular Sciences
N2  - Pharmacologic cardiac conditioning increases the intrinsic resistance against ischemia and reperfusion (I/R) injury. The cardiac conditioning response is mediated via complex signaling networks. These networks have been an intriguing research field for decades, largely advancing our knowledge on cardiac signaling beyond the conditioning response. The centerpieces of this system are the mitochondria, a dynamic organelle, almost acting as a cell within the cell. Mitochondria comprise a plethora of functions at the crossroads of cell death or survival. These include the maintenance of aerobic ATP production and redox signaling, closely entwined with mitochondrial calcium handling and mitochondrial permeability transition. Moreover, mitochondria host pathways of programmed cell death impact the inflammatory response and contain their own mechanisms of fusion and fission (division). These act as quality control mechanisms in cellular ageing, release of pro-apoptotic factors and mitophagy. Furthermore, recently identified mechanisms of mitochondrial regeneration can increase the capacity for oxidative phosphorylation, decrease oxidative stress and might help to beneficially impact myocardial remodeling, as well as invigorate the heart against subsequent ischemic insults. The current review highlights different pathways and unresolved questions surrounding mitochondria in myocardial I/R injury and pharmacological cardiac conditioning.
KW  - cardioprotection
KW  - preconditioning
KW  - ischemia/reperfusion injury
KW  - volatile anesthetics
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285368
SN  - 1422-0067
VL  - 22
IS  - 6
ER  - 
TY  - JOUR
A1  - Jazbutyte, Virginija
A1  - Stumpner, Jan
A1  - Redel, Andreas
A1  - Lorenzen, Johan M.
A1  - Roewer, Norbert
A1  - Thum, Thomas
A1  - Kehl, Franz
T1  - Aromatase Inhibition Attenuates Desflurane-Induced Preconditioning against Acute Myocardial Infarction in Male Mouse Heart In Vivo
JF  - PLoS One
N2  - 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 following 180 minutes reperfusion. Anastrozole blocked DES induced preconditioning and increased infarct size compared to DES alone (37.94615.5% vs. 17.163.62%) without affecting area at risk and systemic hemodynamic parameters following ischemia/reperfusion. Protein localization studies revealed that aromatase was abundant in the murine cardiovascular system with the highest expression levels in endothelial and smooth muscle cells. Desflurane application at pharmacological concentrations efficiently upregulated aromatase expression in vivo and in vitro. We conclude that desflurane efficiently regulates aromatase expression and activity which might lead to increased local estrogen synthesis and thus preserve cellular integrity and reduce cardiac damage in an acute myocardial infarction model.
KW  - smooth muscle cells
KW  - estrogens
KW  - heart
KW  - anesthetics
KW  - immunostaining
KW  - endothelial cells
KW  - gene expression
KW  - myocardial infarction
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151258
VL  - 7
IS  - 8
ER  -