This paper briefly recapitulates the Frank–Starling law of the heart, reviews approaches to establishing diastolic and systolic force–length behaviour in intact isolated cardiomyocytes, and introduces a dimensionless index called ‘Frank–Starling Gain’, calculated as the ratio of slopes of end-systolic and end-diastolic force–length relations. The benefits and limitations of this index are illustrated on the example of regional differences in Guinea pig intact ventricular cardiomyocyte mechanics. Potential applicability of the Frank–Starling Gain for the comparison of cell contractility changes upon stretch will be discussed in the context of intra- and inter-individual variability of cardiomyocyte properties.Electronic supplementary materialThe online version of this article (doi:10.1007/s00424-011-0964-z) contains supplementary material, which is available to authorized users.

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There is a lack of data about the contractile behavior of the right atrial myocardium in chronic pulmonary heart disease. We thoroughly characterized the contractility and Ca transient of isolated right atrial strips of healthy rats (CONT) and rats with the experimental model of monocrotaline-induced pulmonary hypertension (MCT) in steady state at different preloads (isometric force-length), during slow force response to stretch (SFR), and during post-rest potentiation after a period of absence of electrical stimulation (PRP). The preload-dependent changes in the isometric twitch and Ca transient did not differ between CONT and MCT rats while the kinetics of the twitch and Ca transient were noticeably slowed down in the MCT rats. The magnitude of SFR was significantly elevated in the MCT right atrial strips and this was accompanied by the significantly higher elevation of the Ca transient relative amplitude at the end of SFR. The slow changes in the contractility and Ca transient in the PRP protocol did not differ between CONT and MCT. In conclusion, the alterations in the contractility and Ca transient of the right atrial myocardium of monocrotaline-treated rats with pulmonary hypertension mostly concern the elevation in SFR. We hypothesize that this positive inotropic effect in the atrial myocardium may (partly) compensate the systolic deficiency of the right ventricular failing myocardium.

Using one-dimensional models of myocardial tissue, implemented as chains of virtual ventricular muscle segments that are kinematically connected in series, we studied the role of the excitation sequence in spatio-temporal organization of cardiac function. Each model element was represented by a well-verified mathematical model of cardiac electro-mechanical activity. We found that homogeneous chains, consisting of identical elements, respond to non-simultaneous stimulation by generation of complex spatio-temporal heterogeneities in element deformation. These are accompanied by the establishment of marked gradients in local electro-mechanical properties of the elements (heterogeneity in action potential duration, Ca2+ transient characteristics and sarcoplasmic reticulum Ca2+ loading). In heterogeneous chains, composed of elements simulating fast and slow contracting cardiomyocytes from different transmural layers, we found that only activation sequences where stimulation of the slower elements preceded that of faster ones gave rise to optimization of the system's electro-mechanical function, which was confirmed experimentally. Based on the results obtained, we hypothesize that the sequence of activation of cardiomyocytes in different ventricular layers is one of the key factors of spatio-temporal organization of myocardium. Moreover, activation sequence and regional differences in intrinsic electro-mechanical properties of cardiac muscle must be matched in order to optimize myocardial function.

In an earlier study, we experimentally mimicked the effects of mechanical interaction between different regions of the ventricular wall by allowing pairs of independently maintained cardiac muscle fibers to interact mechanically in series or in parallel. This simple physiological model of heterogeneous myocardium, which has been termed "duplex," has provided new insight into basic effects of cardiac electromechanical heterogeneity. Here, we present a novel "hybrid duplex," where one of the elements is an isolated cardiac muscle and the other a "virtual cardiac muscle." The virtual muscle is represented by a computational model of cardiomyocyte electromechanical activity. We present in detail the computer-based digital control system that governs the mechanical interaction between virtual and biological muscle, the software used for data analysis, and working implementations of the model. Advantages of the hybrid duplex method are discussed, and experimental recordings are presented for illustration and as proof of the principle.