Effects of Cardiac Stem Cell on Postinfarction Arrhythmogenic Substrate

Figure 1. Regression line showing the correlation of dense scar volume between week 4 and week 16. (A): Dense scar correlation in the IC+TM CDCs group. (B): Dense scar correlation in the control group. The regression line shows a strong association between dense scars at weeks 4 and 16 in IC+TM group, suggesting scar growth is similar for all sizes of scars. In the control group, the smallest scars grew the most. IC: Intracoronary; TM: Transmyocardial; CDC, Cardiosphere-derived cells.

Figure 2. Upper panel: Optical mapping study showing the APD gradient around the scar. Blue lines represent AP in NZ areas and red lines HT APs. (Upper panel): Epicardial surface of a heart from the IC+TM treated group. The area that was optically mapped (shown inside the green rectangle) includes dense scar (absence of muscle), HT (fibrotic strands separating myocytes bundles), and NZ where no fibrosis is seen. Optical mapping of the area delimited by the green frame shows the APD gradient between HT and NZ; the HT remains green (myocytes are still depolarized), whereas the NZ has turned black (myocytes have repolarized). Below the optical mapping image, the AP of HT and NZ are shown. APs from HT were longer but no differences in amplitude and resting membrane potential were observed. (Lower panel): Optical mapping showing the APD gradient around the scar. On the left, the epicardial surface of a control heart is presented with the area that was optically mapped and delimited by a green rectangle. The figure shows the dense scar (absence of muscle) with intra-scar channels running along epicardial arteries, the HT, characterized by fibrotic strands separating myocytes bundles (red arrow…

Figure 3. Differences between control and IC+TM groups on action potential duration (A) and conduction velocity (B) during optical mapping. (*) Statistically significant p value < 0.05. ISC, epicardial intra-scar channel; HT, heterogeneous tissue; IC, intracoronary; TM, transmyocardial; NZ, normal zone.

Figure 4. (A): Example of a control experiment showing two ISCs of surviving myocardium; the red arrow shows the cross-section of one ISC, revealing viable muscle around the epicardial artery. These channels course along epicardial arteries. These channels served as the central isthmus of an induced VT whose isochron map is shown in (B) (See also Video S1 in online Supplementary Materials). ISCs, intra-scar channels; VT, ventricular tachycardia.

Figure 5. This figure shows the histological differences in dense scars between the control and IC+TM groups. (A): The control group is characterized by the presence of numerous myofibroblasts (brown elongated cells; red arrows) that stain with anti-α-SMA antibodies and that are not related to vessels. (B): In the IC+TM experiment, the anti-α-SMA antibodies only stain the walls of vessels (V) where smooth muscle is present (blue arrow). α-SMA: α-smooth muscle actin.

Figure 6. Characteristics of the fibrotic tissue at the HT in a control experiment. (A): Masson’s Trichrome stains blue the collagen tracts that invade and separate the bundles of myocytes at the border zone. (B): In the same area, anti-α-SMA antibodies reveal the presence of myofibroblasts (brown elongated cells, red arrows) in the collagen tracts separating bundles of myocytes. α-SMA: α-smooth muscle actin.

Figure 7. Distribution of connexin-43 in HT. The dashed red line marks the boundaries between fibrotic tissue and myocyte bundles. (A): connexin-43 (brown bands) distribution in the control group is more irregular than in the IC+TM group (B), in which most myocytes at the border zone were connected to other myocytes by connexin-43 located in intercalated discs.

Figure 8. Flow diagram showing the VT substrate substudy protocol within the protocol that analyzed the effects of CDC on the scar and LV volumes with ceMRI. CDCs: Cardiosphere-derived cells, ce-MRI: contrast-enhanced magnetic resonance imaging, EPS: Electrophysiological Study, IC: Intracoronary, TM: Transmyocardial.

Figure 9. Masson’s Trichrome stain shows a cross-section of the scar with: 1. Central dense scar (blue area devoid of myocytes), 2. Subendocardium, 3. The lateral HT (the area inside the yellow dotted line) in which the external boundary was marked by the tip of the fibrotic strands (blue arrows) and 4. The intra-scar channels. HT: heterogeneous tissue; EISC, epicardial intra-scar channels.