The sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of effective drugs managing patients, who suffer from type 2 diabetes (T2D): Landmark clinical trials including EMPA-REG, CANVAS and Declare-TIMI have demonstrated that SGLT2 inhibitors reduce cardiovascular mortality and re-hospitalization for heart failure (HF) in patients with T2D. It is well established that there is a strong independent relationship among infarct size measured within 1 month after reperfusion and all-cause death and hospitalization for HF: The fact that cardiovascular mortality was significantly reduced with the SGLT2 inhibitors, fuels the assumption that this class of therapies may attenuate myocardial infarct size. Experimental evidence demonstrates that SGLT2 inhibitors exert cardioprotective effects in animal models of acute myocardial infarction through improved function during the ischemic episode, reduction of infarct size and a subsequent attenuation of heart failure development. The aim of the present review is to outline the current state of preclinical research in terms of myocardial ischemia/reperfusion injury (I/R) and infarct size for clinically available SGLT2 inhibitors and summarize some of the proposed mechanisms of action (lowering intracellular Na+ and Ca2+, NHE inhibition, STAT3 and AMPK activation, CamKII inhibition, reduced inflammation and oxidative stress) that may contribute to the unexpected beneficial cardiovascular effects of this class of compounds.

中文翻译：

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在临床前模型中，SGLT2抑制剂可减少缺血再灌注心脏的梗塞面积并改善其心脏功能。

钠葡萄糖共转运蛋白2（SGLT2）抑制剂是一类有效的新型药物，可治疗2型糖尿病（T2D）患者：具有里程碑意义的临床试验包括EMPA-REG，CANVAS和Declare-TIMI已证明SGLT2抑制剂可降低心血管疾病T2D患者的病死率和心衰（HF）的再次住院治疗。公认的是，在再灌注后1个月内测得的梗塞面积与HF的全因死亡和住院之间存在很强的独立关系：使用SGLT2抑制剂可显着降低心血管死亡率，这一事实加剧了这一假设：治疗可以减轻心肌梗塞的大小。实验证据表明，SGLT2抑制剂可通过在缺血性发作期间改善功能，减少梗塞面积并随后减轻心力衰竭的发展，在急性心肌梗塞的动物模型中发挥心脏保护作用。本综述的目的是就临床上可用的SGLT2抑制剂的心肌缺血/再灌注损伤（I / R）和梗死面积概述临床前研究的现状，并概述一些拟议的作用机制（降低细胞内Na +和Ca2 +，NHE抑制，STAT3和AMPK激活，CamKII抑制，减少的炎症和氧化应激）可能有助于此类化合物的意料之外的有益心血管作用。减少梗塞面积并随后减轻心力衰竭的发展。本综述的目的是就临床上可用的SGLT2抑制剂的心肌缺血/再灌注损伤（I / R）和梗死面积概述临床前研究的现状，并概述一些拟议的作用机制（降低细胞内Na +和Ca2 +，NHE抑制，STAT3和AMPK激活，CamKII抑制，减少的炎症和氧化应激）可能有助于此类化合物的意料之外的有益心血管作用。减少梗塞面积并随后减轻心力衰竭的发展。本综述的目的是就临床上可用的SGLT2抑制剂的心肌缺血/再灌注损伤（I / R）和梗死面积概述临床前研究的现状，并概述一些拟议的作用机制（降低细胞内Na +和Ca2 +，NHE抑制，STAT3和AMPK激活，CamKII抑制，减少的炎症和氧化应激）可能有助于此类化合物的意料之外的有益心血管作用。