The beneficial effects of empagliflozin (EMPA) on cardiac functions during ischemia and reperfusion were characterized. The contractile functions of isolated cardiomyocytes from adult C57BL/6J mice were determined with IonOptix SoftEdgeMyoCam system. The mitochondrial superoxide production was measured by MitoSOX fluorescent probe. The ex vivo isolated heart perfusion system was used to determine the pharmacological effects of EMPA on heart's contractile functions under both physiological and pathological conditions. The in vivo regional myocardial ischemia and reperfusion by ligation of left artery coronary artery descending (LAD) was used to measure the myocardial infarction caused by ischemia and reperfusion with or without EMPA treatment. The results demonstrated that EMPA treatment significantly improves cardiomyocyte contractility under hypoxia conditions and augments the post-ischemic recovery in the ex vivo heart perfusion system. Furthermore, the in vivo myocardial infarction measurement shows that EMPA treatment significantly reduce myocardial infarct size caused by ischemia and reperfusion. The biochemical analysis demonstrated that EMPA can trigger cardiac AMPK signaling pathway and attenuate mitochondrial superoxide production under hypoxia and reoxygenation conditions. In conclusion, EMPA can trigger AMPK signaling pathways and modulate myocardial contractility and reduce myocardial infarct size caused by ischemia and reperfusion independent of hypoglycemic effect. The results for the first time demonstrate that the activation of AMPK by EMPA could one reason about EMPA's beneficial effects on heart disease.

中文翻译：

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Empagliflozin可通过LKB1 / AMPK信号通路减轻缺血和再灌注损伤。

表征了依帕列净（EMPA）对缺血和再灌注期间心脏功能的有益作用。使用IonOptix SoftEdgeMyoCam系统确定来自成年C57BL / 6J小鼠的分离的心肌细胞的收缩功能。通过MitoSOX荧光探针测量线粒体超氧化物的产生。离体离体心脏灌注系统用于确定EMPA在生理和病理条件下对心脏收缩功能的药理作用。通过结扎左动脉冠状动脉降支（LAD）进行体内局部心肌缺血和再灌注，以测量缺血或再灌注引起的心肌梗塞（有或没有EMPA治疗）。结果表明，EMPA治疗可显着改善缺氧条件下的心肌收缩力，并增强离体心脏灌注系统的缺血后恢复能力。此外，体内心肌梗塞的测量结果表明，EMPA治疗可显着减少由缺血和再灌注引起的心肌梗塞面积。生化分析表明，EMPA可以在缺氧和复氧条件下触发心脏AMPK信号通路并减弱线粒体超氧化物的产生。总之，EMPA可以触发AMPK信号通路并调节心肌收缩力，并减少由缺血和再灌注引起的心肌梗塞面积，而与降血糖作用无关。