Department of Cardiology, University Hospitals Coventry & Warwickshire, Coventry, CV2 2DX, UK.
Centre for Sport, Exercise & Life Sciences, Faculty of Health and Life Sciences, Alison Gingell Building, Coventry University, Coventry, CV1 2DS, UK.
Curr Cardiol Rep. 2022 Jun;24(6):711-730. doi: 10.1007/s11886-022-01689-2. Epub 2022 Mar 30.
This review combines existing mechano-energetic principles to provide a refreshing perspective in heart failure (HF) and examine if the phenomenon of myocardial fatigue can be rigorously tested in vitro with current technological advances as a bridge between pre-clinical science and clinical practice.
As a testament to the changing paradigm of HF pathophysiology, there has been a shift of focus from structural to functional causes, as reflected in its modern universal definition and redefined classification. Bolstered by recent landmark trials of sodium-glucose cotransport-2 inhibitors across the HF spectrum, there is a rekindled interest to revisit the basic physiological tenets of energetic efficiency, metabolic flexibility, and mechanical load on myocardial performance. Indeed, these principles are well established in the study of skeletal muscle fatigue. Since both striated muscles share similar sarcomeric building blocks, is it possible that myocardial fatigue can occur in the face of sustained adverse supra-physiological load as a functional cause of HF? Myocardial fatigue is a mechano-energetic concept that offers a novel functional mechanism in HF. It is supported by current studies on exercise-induced cardiac fatigue and reverse translational science such as from recent landmark trials on sodium glucose co-transporter 2 inhibitors in HF. We propose a novel framework of myocardial fatigue, injury, and damage that aligns with the contemporary notion of HF as a continuous spectrum, helps determine the chance and trajectory of myocardial recovery, and aims to unify the plethora of cellular and molecular mechanisms in HF.
本文综合现有的机械能量学原理，为心力衰竭（HF）提供新视角，并探讨心肌疲劳现象能否在体外通过当前技术进步进行严格测试，从而在临床前科学和临床实践之间架起桥梁。
随着 HF 病理生理学范式的转变，人们的关注点已经从结构性原因转移到功能性原因，这反映在其现代通用定义和重新定义的分类中。最近 HF 谱中钠-葡萄糖共转运蛋白 2 抑制剂的里程碑式试验进一步证实了这一点，人们重新燃起了兴趣，重新审视能量效率、代谢灵活性和机械负荷对心肌性能的基本生理原理。事实上，这些原理在骨骼肌疲劳研究中已得到充分证实。由于横纹肌具有相似的肌节结构，那么在面对持续的超生理负荷时，心肌是否会出现疲劳，这是否是 HF 的一种功能性原因？心肌疲劳是一种机械能量学概念，为 HF 提供了一种新的功能性机制。它得到了关于运动诱导性心肌疲劳的现有研究以及反向转化科学的支持，如最近 HF 中钠葡萄糖共转运蛋白 2 抑制剂的里程碑式试验。我们提出了一种新的心肌疲劳、损伤和损伤框架，与 HF 作为连续谱的现代概念一致，有助于确定心肌恢复的机会和轨迹，并旨在统一 HF 中众多的细胞和分子机制。
