Effect of transmurally heterogeneous myocyte excitation-contraction coupling on canine left ventricular electromechanics - PubMed (original) (raw)

Comparative Study

Effect of transmurally heterogeneous myocyte excitation-contraction coupling on canine left ventricular electromechanics

Stuart G Campbell et al. Exp Physiol. 2009 May.

Abstract

The excitation-contraction coupling properties of cardiac myocytes isolated from different regions of the mammalian left ventricular wall have been shown to vary considerably, with uncertain effects on ventricular function. We embedded a cell-level excitation-contraction coupling model with region-dependent parameters within a simple finite element model of left ventricular geometry to study effects of electromechanical heterogeneity on local myocardial mechanics and global haemodynamics. This model was compared with one in which heterogeneous myocyte parameters were assigned randomly throughout the mesh while preserving the total amount of each cell subtype. The two models displayed nearly identical transmural patterns of fibre and cross-fibre strains at end-systole, but showed clear differences in fibre strains at earlier points during systole. Haemodynamic function, including peak left ventricular pressure, maximal rate of left ventricular pressure development and stroke volume, were essentially identical in the two models. These results suggest that in the intact ventricle heterogeneously distributed myocyte subtypes primarily impact local deformation of the myocardium, and that these effects are greatest during early systole.

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Figures

Figure 1

Depiction of finite element meshes and myocyte subtype distribution used in this study. (A) Left ventricular geometry was approximated as a truncated elipse of revolution with embedded fibres. White and black lines show orientation of endocardial and epicardial fibres, respectively. (B) In the BASELINE simulation, myocyte subtype was set as a proportion of wall thickness to be 1:2:1 endo:mid:epi. Their spatial distribution is shown here superimposed on the two-dimensional mesh used for solution of electrical propagation across the ventricular wall. (C) In the HOM simulation, myocyte subtypes were assigned randomly throughout the mesh while preserving the total volume of each subtype to be equal that used in the BASELINE simulation.

Figure 2

Myocardial activation time as calculated in the BASELINE simulation. Activation was the result of simultaneously stimulating the entire endocardial surface.

Figure 3

Comparison of model-generated fibre (Eff) and cross-fibre (Ecc) strains at end-systole (A) with those reported experimentally in the study of Mazhari et al. (2001) (B). BASELINE and HOM simulations produced essentially identical transmural patterns of fibre and crossfibre strains in spite of different spatial arrangement of myocyte subtypes. End-systolic strains produced by the models displayed transmural patterns that were in good agreement with experimental measurements.

Figure 4

Comparison of time courses of fibre strain (Eff) in models and experiments. Time courses have been normalised to the length of the systolic interval in each case, with dotted vertical lines indicating aortic valve opening. Shaded lines in panels A and B represent fibre strains at wall depths between the heavier lines corresponding to epi-, mid-, and endocardial depths as labelled. Experimentally measured strains (panel C) were obtained in an anesthetized adult dogs (n = 6) using radiopaque beads implanted in the LV free wall. Plotted values represent means ± S.D. of maximum and minimum fibre strains at each time point across animals.

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Effect of transmurally heterogeneous myocyte excitation-contraction coupling on canine left ventricular electromechanics - PubMed (original) (raw)