Markhasin V S, Solovyova O, Katsnelson L B, Protsenko Yu, Kohl P, Noble D
Institute of Ecology and Genetics of Microorganisms, Ural Division of the Russian Academy of Sciences, 91, Pervomayskaya Street, 620219, Ekaterinburg, Russia.
Prog Biophys Mol Biol. 2003 May-Jul;82(1-3):207-20. doi: 10.1016/s0079-6107(03)00017-8.
The heart is structurally and functionally a highly non-homogenous organ, yet its main function as a pump can only be achieved by the co-ordinated contraction of millions of ventricular cells. This apparent contradiction gives rise to the hypothesis that 'well-organised' inhomogeneity may be a pre-requisite for normal cardiac function. Here, we present a set of novel experimental and theoretical tools for the study of this concept. Heterogeneity, in its most condensed form, can be simulated using two individually controlled, mechanically interacting elements (duplex). We have developed and characterised three different types of duplexes: (i) biological duplex, consisting of two individually perfused biological samples (like thin papillary muscles or a trabeculae), (ii) virtual duplex, made-up of two interacting mathematical models of cardiac muscle, and (iii) hybrid duplex, containing a biological sample that interacts in real-time with a virtual muscle. In all three duplex types, in-series or in-parallel mechanical interaction of elements can be studied during externally isotonic, externally isometric, and auxotonic modes of contraction and relaxation. Duplex models, therefore, mimic (patho-)physiological mechano-electric interactions in heterogeneous myocardium at the multicellular level, and in an environment that allows one to control mechanical, electrical and pharmacological parameters. Results obtained using the duplex method show that: (i) contractile elements in heterogeneous myocardium are not 'independent' generators of tension/shortening, as their ino- and lusitropic characteristics change dynamically during mechanical interaction-potentially matching microscopic contractility to macroscopic demand, (ii) mechanical heterogeneity contributes differently to action potential duration (APD) changes, depending on whether mechanical coupling of elements is in-parallel or in-series, which may play a role in mechanical tuning of distant tissue regions, (iii) electro-mechanical activity of mechanically interacting contractile elements is affected by their activation sequence, which may optimise myocardial performance by smoothing intrinsic differences in APD. In conclusion, we present a novel set of tools for the experimental and theoretical investigation of cardiac mechano-electric interactions in healthy and/or diseased heterogeneous myocardium, which allows for the testing of previously inaccessible concepts.
心脏在结构和功能上是一个高度非均质的器官，然而它作为泵的主要功能只能通过数百万心室细胞的协同收缩来实现。这种明显的矛盾引发了一种假说，即“组织良好”的非均质性可能是正常心脏功能的一个先决条件。在此，我们提出了一套用于研究这一概念的新颖实验和理论工具。异质性，以其最浓缩的形式，可以使用两个单独控制、机械相互作用的元件（双联体）来模拟。我们已经开发并表征了三种不同类型的双联体：（i）生物双联体，由两个单独灌注的生物样本（如细乳头肌或小梁）组成，（ii）虚拟双联体，由两个相互作用的心肌数学模型组成，以及（iii）混合双联体，包含一个与虚拟肌肉实时相互作用的生物样本。在所有三种双联体类型中，可以在外部等张、外部等长和辅助等张收缩和舒张模式下研究元件的串联或并联机械相互作用。因此，双联体模型在多细胞水平上模拟了异质性心肌中的（病理）生理机电相互作用，并且在一个允许控制机械、电和药理学参数的环境中进行模拟。使用双联体方法获得的结果表明：（i）异质性心肌中的收缩元件不是张力/缩短的“独立”产生者，因为它们的变力和变时特性在机械相互作用期间动态变化——潜在地使微观收缩性与宏观需求相匹配，（ii）机械异质性对动作电位持续时间（APD）变化的贡献不同，这取决于元件的机械耦合是并联还是串联，这可能在远处组织区域的机械调节中起作用，（iii）机械相互作用的收缩元件的机电活动受其激活顺序的影响，这可能通过平滑APD的内在差异来优化心肌性能。总之，我们提出了一套新颖的工具，用于对健康和/或患病的异质性心肌中的心脏机电相互作用进行实验和理论研究，这使得能够测试以前无法触及的概念。
