Structural, functional, and biochemical heterogeneity of myocardial tissue has been documented at different levels of functional integration, from molecular to whole organ. In isolated cells, transmural heterogeneity of biochemical properties, electrical and mechanical characteristics, and excitation-contraction coupling have been experimentally confirmed. There are, however, a many unresolved question, such as: How does cellular heterogeneity correlate with mechanical conditions and the electrical activation sequence in the intact heart? What is the physiological significance of myocardial heterogeneity? How does it affect pathologies? To study basic effects of the dynamic interaction between myocardial elements on the electro-mechanical function of a heterogeneous system, we developed a condensed model of cardiac heterogeneity, termed ‘duplex’. A duplex consists of a pair of interacting cardiac muscle preparations that are mechanically interconnected. We have implemented six duplex configurations [1], based on mechanical connection of elements in-parallel or in-series, using all possible combinations of biological and/or virtual muscle segments. The combinations are: i) biological duplex (two biological samples, such as thin papillary muscles or trabeculae); ii) virtual duplex (two mechanically interacting mathematical models of cardiac muscle); and iii) hybrid duplex (combination of a biological sample and a model-driven I/O system that interact mechanically in real-time). For all duplex configurations, we studied the mechanical activity of each individual element in isolation, and after coupling within a duplex, during isometric, isotonic, and auxotonic modes of contraction. Introducing different time lags between element stimulation, we furthermore studied effects of the electrical excitation sequence on duplex function. We found that, the contractile function of each individual element (quantitatively assessed as length-force and force-velocity relations) is significantly affected by the dynamic interaction of elements (representing a model of the in situ mechanical environment), depending on individual mechanical properties, electrical activation sequence, and connection pattern of elements. Using virtual duplexes, we showed that mechanical interaction between functionally heterogeneous virtual muscle elements affects their electrical activity in the sense of mechano-electrical feedback (MEF). The models yielded opposite changes in the action potential duration (APD) of elements after duplex formation (both in-parallel and in-series), where an increase in APD of one virtual muscle correlates to a decrease in the other. The sense of that APD change depends critically on the excitation sequence. As a result, dispersion of repolarisation within the duplex is significantly different from that observed in uncoupled muscles, and varied from zero to values that significantly exceeded intrinsic activation delay times. This prediction may explain contradictory data on dispersion of repolarisation, experimentally registered in either isolated cells or in intact tissue. From modelling results we derived mechanisms that are possibly responsible for the effects of heterogeneity on duplex electromechanical function. We conclude that functional alteration of the electromechanical activity of duplex elements involves complex interplay of cellular processes, where mechano-dependent Ca²⁺ kinetics (via co-operative modulation of Ca2+ binding to troponin C, and influence on Ca²⁺ dependent ionic currents) plays a key role in the tuning of mechanical and electrical activity. Additional effects of stretch-activated channels are subject of further investigation. Along with rapid responses of coupled muscles to change in external conditions (e.g. excitation sequence, duplex length, afterload) we studied more slowly occurring changes in steady state behaviour. Particularly, we assessed SR Ca²⁺ levels in duplex elements (either directly by calculating this in virtual muscle or indirectly by registering force change in real muscle) before and after mechanical coupling. We found in hybrid and virtual duplexes that there is a relative re-distribution of SR Ca²⁺ load between mechanically interacting elements, even in the absence of common Ca²⁺ source. This could shed light on one of the potential physiological relevance of MEF in heterogeneous myocardium, which could be related to the maintenance of an adequate Ca²⁺ load in the individual cells of the heart, to optimize their function.