目的:多项随机对照试验已将SGLT2抑制剂(SGLT2i)作为心力衰竭患者的新型药物治疗,导致心力衰竭住院和死亡率降低。考虑到心脏中没有SGLT2受体,SGLT2i的直接心脏保护作用机制复杂,尚待研究.在这项研究中,我们评估了SGLT2iempagliflozin对终末期心力衰竭患者离体心肌的直接生物力学效应.
方法:将7例接受心脏移植或心室辅助装置植入手术的患者的心室组织活检切成27个活体心肌切片(LMS),并安装在定制的培养室中,并带有机械预加载和电刺激,导致心脏收缩。对这些300µm厚的LMS进行10µMempagliflozin处理,并连续记录生物力学参数。
结果:Empagliflozin不影响切片的最大收缩力,然而,总收缩持续时间增加了13%(p=0.002),这是通过延长达到峰值的时间和松弛时间(分别为p=0.009和p=0.003)确定的。
结论:在仿生系统中培养的终末期心力衰竭患者的LMS中添加依帕列净可通过增加总收缩持续时间而不减少最大力的产生来改善收缩和松弛动力学。因此,我们提供了令人信服的证据,证明SGLT2i在没有来自其他器官系统的全身影响的情况下可以直接作用于心肌.
OBJECTIVE: Multiple randomized controlled trials have presented SGLT2 inhibitors (SGLT2i) as novel pharmacological therapy for patients with heart failure, resulting in reductions in hospitalization for heart failure and mortality. Given the absence of SGLT2 receptors in the heart, mechanisms of direct cardioprotective effects of SGLT2i are complex and remain to be investigated. In this study, we evaluated the direct biomechanical effects of SGLT2i empagliflozin on isolated myocardium from end-stage heart failure patients.
METHODS: Ventricular tissue biopsies obtained from 7 patients undergoing heart transplantation or ventricular assist device implantation surgery were cut into 27 living myocardial slices (LMS) and mounted in custom-made cultivation chambers with mechanical preload and electrical stimulation, resulting in cardiac contractions. These 300 µm thick LMS were subjected to 10 µM empagliflozin and with continuous recording of biomechanical parameters.
RESULTS: Empagliflozin did not affect the maximum contraction force of the slices, however, increased total contraction duration by 13% (p = 0.002) which was determined by prolonged time to peak and time to relaxation (p = 0.009 and p = 0.003, respectively).
CONCLUSIONS: The addition of empagliflozin to LMS from end-stage heart failure patients cultured in a biomimetic system improves contraction and relaxation kinetics by increasing total contraction duration without diminishing maximum force production. Therefore, we present convincing evidence that SGLT2i can directly act on the myocardium in absence of systemic influences from other organ systems.