National Heart & Lung Institute, Imperial College London, London, UK.
Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois, USA.
Exp Physiol. 2024 Mar;109(3):405-415. doi: 10.1113/EP091247. Epub 2023 Oct 17.
Mechanical load is one of the main determinants of cardiac structure and function. Mechanical load is studied in vitro using cardiac preparations together with loading protocols (e.g., auxotonic, isometric). However, such studies are often limited by reductionist models and poorly simulated mechanical load profiles. This hinders the physiological relevance of findings. Living myocardial slices have been used to study load in vitro. Living myocardial slices (LMS) are 300-μm-thick intact organotypic preparations obtained from explanted animal or human hearts. They have preserved cellular populations and the functional, structural, metabolic and molecular profile of the tissue from which they are prepared. Using a three-element Windkessel (3EWK) model we previously showed that LMSs can be cultured while performing cardiac work loops with different preload and afterload. Under such conditions, LMSs remodel as a function of the mechanical load applied to them (physiological load, pressure or volume overload). These studies were conducted in commercially available length actuators that had to be extensively modified for culture experiments. In this paper, we demonstrate the design, development and validation of a novel device, MyoLoop. MyoLoop is a bioreactor that can pace, thermoregulate, acquire and process data, and chronically load LMSs and other cardiac tissues in vitro. In MyoLoop, load is parametrised using a 3EWK model, which can be used to recreate physiological and pathological work loops and the remodelling response to these. We believe MyoLoop is the next frontier in basic cardiovascular research enabling reductionist but physiologically relevant in vitro mechanical studies.
机械负荷是心脏结构和功能的主要决定因素之一。在体外，通过心脏制剂和加载方案（例如，等张、等容）来研究机械负荷。然而，此类研究常常受到简化模型和模拟机械负荷曲线效果不佳的限制。这阻碍了研究结果的生理相关性。活体心肌切片已被用于体外负荷研究。活体心肌切片（LMS）是从离体动物或人心脏获得的 300μm 厚的完整器官型制剂。它们保留了细胞群体以及它们所制备组织的功能、结构、代谢和分子特征。我们之前使用三元素风箱（3EWK）模型表明，LMS 可以在进行不同预载和后载的心脏工作循环的同时进行培养。在这种情况下，LMS 会根据施加给它们的机械负荷（生理负荷、压力或容量过载）进行重塑。这些研究是在商业上可用的长度作动器上进行的，这些作动器必须经过大量修改才能用于培养实验。在本文中，我们展示了一种新型设备 MyoLoop 的设计、开发和验证。MyoLoop 是一种生物反应器，可起搏、温度调节、采集和处理数据，并在体外对 LMS 和其他心脏组织进行慢性加载。在 MyoLoop 中，使用 3EWK 模型对负荷进行参数化，该模型可用于重现生理和病理工作循环以及对这些循环的重塑反应。我们相信 MyoLoop 是基础心血管研究的下一个前沿领域，它可以实现简化但具有生理相关性的体外机械研究。
