Myocardial slices come to age: an intermediate complexity in vitro cardiac model for translational research

Figure 1. Cardiac slices. (A) Heart slice cartoon. Note that thickness is one order of magnitude less than width or length. As a result, slices have been described as pseudo-2D. (B) Heart slice. After the vibratome cuts through the heart tissue, a heart slice is obtained (B, left). This is subsequently trimmed using razor blades to a rectangle, typically 10 × 8 mm in dimensions, with the myofibres oriented along the long axis (B, right) of the slice. B adapted from Watson et al.1

Figure 2. Number of published papers using myocardial slices between the years 1943 and 2019. One hundred and eighty-one papers were identified in a literature search.

Figure 3. Canine myocardial slices. (A) Cardiac populations of a dog myocardial slice visualized under confocal microscopy. α-smooth muscle actin (white) was used to identify large vessels, isolectin for endothelial cells (green), and vimentin for mesenchymal cells (red). (B) Capillary network in a freshly prepared dog myocardial slice. Cardiomyocytes labelled with caveolin-3 (red) and endothelial cells with isolectin (white). Figure adapted from Perbellini et al.18

Figure 4. Experimental data acquired using myocardial slices. (A) Twitch force trace of human HF slices paced at 0.5 Hz. (B) ATP and ADP peaks from high-performance liquid chromatography for metabolic studies. (C) Effects of chronic pentamidine exposure on action potential in cultured human slices. (D) T-tubule density and regularity of cultured rat slices. (E) Conduction maps of freshly prepared human HF slices (left, right: longitudinal, transverse conduction velocity, respectively). (F) Second harmonic imaging of a slice that has been optically cleared using FASTClear. A and E adapted from Watson et al.1; B from Camelliti et al.26; C from Watson et al.8; D modified from Fischer et al.7; and F from Perbellini et al.72

Figure 5. Culture systems developed by Fischer et al. (A and C), and Watson et al. (B and D), for prolonged maintenance of adult cardiac tissue in vitro. (A) Culture chamber developed by Fischer et al., consisting of one inflexible and one flexible post allowing for auxotonic contractions, and graphite blocks for electrical stimulation. (B) Culture chamber developed by Watson et al. The chamber can accommodate up to four stainless steel stretchers and each stretcher mounts one slice. The system consists of graphite electrodes, perfusion and O2 inlets/outlets. (C) This culture system allows measurements of contractility by monitoring displacement of the flexible post, quantified using a magnetic plate and the stiffness constant of the post. (D) Stretchers allow for manipulation of preload by changing the muscle length of the mounted slice. The stretchers posts are inflexible so that the muscle contracts isometrically. Scale bars: 10 mm. A and C adapted from Fischer et al.7 and B and D from Watson et al.8

Figure 6. Computer simulations of force-length changes under the culture chambers developed by Fischer et al. (A) and Watson et al. (B) vs. the in vivo state (C). (A) In the system by Fischer et al., the slices generate force while shortening in a linear manner. (B) In the system by Watson et al., slices contract isometrically, that is, generate force without corresponded changes in length. (C) In vivo, the myocardium develops force while shortening in a more intricate fashion consisting of distinct phases whereby force is changing without length changes, and where both are changing simultaneously.