Thickening of the Infarcted Wall by Collagen Injection Improves Left Ventricular Function in Rats
A Novel Approach to Preserve Cardiac Function After Myocardial Infarction
Wangde Dai, MD,
Loren E. Wold, PhD,
Joan S. Dow, BS and
Robert A. Kloner, MD, PhD*
The Heart Institute, Good Samaritan Hospital, Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
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Figure 1 Left ventricular ejection fraction (LVEF) calculated by angiography at six weeks after collagen or saline injection directly into the scar area of myocardial infarction in rats. For rats that received collagen, LVEF was 48.4 ± 1.8% (n = 11). For rats that received saline, LVEF (40.7 ± 1.0%, n = 10) was significantly lower than that in the collagen-treated group (*p = 0.002).
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Figure 2 (A) Low-power slices of left ventricles stained with picrosirius red staining. Muscle cells stain yellow, whereas collagen stains red. The section shows that implanted collagen thickens the wall (blue arrows) of the six-week-old myocardial infarct scar area with bright red collagen. (B) Saline-treated heart with six-week-old myocardial infarct (black arrows). Note the staining of the infarct scar collagen in the thin free wall of the left ventricle is much less intense than that of the implanted collagen (bright red staining).
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Figure 3 (A, B) Higher power view of the boxed area in Figure 2A. Picrosirius red-stained sections of collagen implanted into myocardial infarct scar area. The bright red-stained implanted collagen is in the center of the scar (A, B; black arrows), and the scar is divided into endocardial and epicardial portions (A: x40; B: x100). (C) Higher power view (x400) of Figure 3B show the border (black arrows) between the collagen implant (left side) and the native collagen deposition (right side). The collagen implant is homogeneous. There is no bundle formation as in native collagen deposition. (D) Picrosirius red staining of in vitro collagen for implantation. The collagen staining is bright red and homogeneous, similar to that shown in Figure 3C (collagen-treated) (x400). (E, F) Higher power view of the boxed area in Figure 2B. Picrosirius red-stained sections of a six-week-old saline-treated myocardial infarct scar area. Red staining shows the collagen deposition, whereas yellow shows the viable myocardium in the scar, and the blue staining shows the blood vessels (E: x40; F: x100). In contrast, note that no blue dye is found in the implanted collagen area in Figures 3A and 3B, and collagen deposition is much more intense in Figures 3A and 3B (collagen-treated) compared with Figures 3E and 3F (saline-treated).
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Figure 4 (A, B) Hematoxylin and eosin staining of the slices in Figure 2A. The white dashed line (white arrow) shows the border between the collagen implant (left side) and the native collagen deposition (right side). The collagen implant is homogeneous red without cells within the implant. The native collagen deposition shows bundle formation with cells (yellow arrows) (A: x200, B: x400). C Hematoxylin and eosin staining of in vitro collagen for implantation. The collagen staining is bright red and homogeneous, similar to that shown in Figure 4B (collagen-treated) (x400).
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Figure 5 Verhoeff's stain for elastic tissue staining of the slices in Figure 2A. Elastic fibers stain black, whereas collagen stains red. The white dashed line (white arrow) shows the border between the collagen implant (left side) and the native collagen deposition (right side). The collagen implant is homogeneous without elastic fibers within the implant. The native collagen deposition demonstrates bundle formation with elastic fibers (yellow arrows) (x400).
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