Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.
Department of Engineering Science and Biomedical Engineering, The University of Auckland, Auckland, New Zealand.
Am J Physiol Heart Circ Physiol. 2023 Nov 1;325(5):H1223-H1234. doi: 10.1152/ajpheart.00272.2023. Epub 2023 Sep 15.
Isolated cardiac tissues allow a direct assessment of cardiac muscle function and enable precise control of experimental loading conditions. However, current experimental methods do not expose isolated tissues to the same contraction pattern and cardiovascular loads naturally experienced by the heart. In this study, we implement a computational model of systemic-pulmonary impedance that is solved in real time and imposed on contracting isolated rat muscle tissues. This systemic-pulmonary model represents the cardiovascular system as a lumped-parameter, closed-loop circuit. The tissues performed force-length work-loop contractions where the model output informed both the shortening and restretch phases of each work-loop. We compared the muscle mechanics and energetics associated with work-loops driven by the systemic-pulmonary model with that of a model-based loading method that only accounts for shortening. We obtained results that show simultaneous changes of afterload and preload or end-diastolic length of the muscle, as compared with the static, user-defined preload as in the conventional loading method. This feature allows assessment of muscle work output, heat output, and efficiency of contraction as functions of end-diastolic length. The results reveal the behavior of cardiac muscle as a pump source to achieve load-dependent work and efficiency outputs over a wider range of loads. This study offers potential applications of the model to investigate cardiac muscle response to hemodynamic coupling between systemic and pulmonary circulations in an in vitro setting. We present the use of a "closed-loop" model of systemic and pulmonary circulations to apply, for the first time, real-time model-calculated preload and afterload to isolated cardiac muscle preparations. This method extends current experimental protocols where only afterload has been considered. The extension to include preload provides the opportunity to investigate ventricular muscle response to hemodynamic coupling and as a pump source across a wider range of cardiovascular loads.
分离的心肌组织可以直接评估心肌功能，并能够精确控制实验加载条件。然而，目前的实验方法并没有使分离的组织暴露于心脏自然经历的相同收缩模式和心血管负荷下。在这项研究中，我们实现了一个系统-肺阻抗的计算模型，该模型实时求解，并施加于收缩的离体大鼠肌肉组织上。这个系统-肺模型将心血管系统表示为一个集总参数、闭环电路。组织进行力-长度工作环收缩，其中模型输出为每个工作环的缩短和再拉伸阶段提供信息。我们将由系统-肺模型驱动的肌肉力学和能量学与仅考虑缩短的基于模型的加载方法进行了比较。我们得到的结果表明，与传统加载方法中静态、用户定义的预载相比，肌肉的后负荷和前负荷或舒张末期长度同时发生变化。这个特征允许评估肌肉工作输出、热输出和收缩效率作为舒张末期长度的函数。结果揭示了心脏肌肉作为泵源的行为，以在更宽的负荷范围内实现与负荷相关的工作和效率输出。这项研究为模型在体外环境中研究系统和肺循环之间的血液动力学耦合对心肌的响应提供了潜在的应用。我们提出了使用系统和肺循环的“闭环”模型，首次将实时模型计算的前负荷和后负荷应用于离体心肌标本。这种方法扩展了目前仅考虑后负荷的实验方案。将前负荷包括在内提供了研究心室肌肉对血液动力学耦合的响应以及作为泵源的机会，可以在更宽的心血管负荷范围内进行。
