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Scintigraphic Assessment of the Effects of Bone Marrow–Derived Mononuclear Cell Transplantation Combined with Off-Pump Coronary Artery Bypass Surgery in Patients with Ischemic Heart Disease

Hiroyuki Yaoita, MD1, Shinya Takase, MD2, Yukio Maruyama, MD1, Yoshiyuki Sato, MD2, Hirono Satokawa, MD2, Nobuo Hoshi, MD3, Nobutaka Ono, MD4, Tsuguo Igari, MD5, Hitoshi Ohto, MD5 and Hitoshi Yokoyama, MD2

1 First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan
2 Department of Cardiovascular Surgery, Fukushima Medical University, Fukushima, Japan
3 Second Department of Pathology, Fukushima Medical University, Fukushima, Japan
4 Shirakawa Kousei General Hospital, Shirakawa, Japan
5 Division of Blood Transfusion and Transplantation Immunology, Fukushima Medical University, Fukushima, Japan



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FIGURE 1. Myocardial uptake of 99mTc-tetrofosmin on dipyridamole-stress (A) and at resting condition (B) before and 1 mo after OPCAB and BMCT in regions of no ischemia (control), OPCAB, and BMCT treatment. {circ}, Control sites; {triangleup}, OPCAB sites; {boxplus}, BMCT sites (n = 10 each). *P < 0.05 vs. before OPCAB + BMCT. (C) Comparison of myocardial uptake of 99mTc-tetrofosmin on dipyridamole-stress among different methods for bone marrow–derived mononuclear cell correction by G-CSF and apheresis or by bone marrow aspiration. {square}, Sites of BMCT by G-CSF and apheresis; {blacksquare}, sites of BMCT by bone marrow aspiration (n = 5 each). *P < 0.05 vs. before OPCAB + BMCT.

 


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FIGURE 2. Relation between CD34+ (A and C) or total number of mononuclear cells (B and D) and changes (ratios) in myocardial uptake (myocardial 99mTc uptake 1 mo after BMCT/myocardial 99mTc uptake before BMCT) on dipyridamole-stress (A and B) and at rest (C and D) in 10 patients. Plots in A–D are from the same patient. Only A showed a significant relation between x- and y-axes: Changes in myocardial uptake on stress = 1.091 x (CD34+ cell number [x106])0.074 (r2 = 0.48).

 


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FIGURE 3. A representative case: patient 2. Polar maps on myocardial 99mTc perfusion SPECT during dipyridamole-stress and at rest, and time–volume curve (volume [mL]/interval) on QGS (from left to right) before and 1 and 5 mo after OPCAB and BMCT. Compared with before, after OPCAB and BMCT, myocardial perfusion on dipyridamole-stress was ameliorated in posterolateral wall (BMCT site) and anterolateral wall (OPCAB site), although myocardial perfusion at rest was unchanged. LVEF increased 5 mo after compared with before OPCAB and BMCT. LVEDV = LV end-diastolic volume.

 


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FIGURE 4. Myocardial CD34+ vessel densities in areas of control (nonischemic), OPCAB, BMCT, and old myocardial infarction. There were 3 patients each in control, OPCAB, and BMCT (total n = 63) areas and 2 patients in old infarction area (n = 14). *P < 0.05 vs. control area; {dagger}P < 0.0001 vs. control area; {ddagger}P < 0.05 vs. OPCAB area; §P < 0.0001 vs. old infarction area.

 


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FIGURE 5. Histopathogic findings at autopsy: patient 2. Light microscopic findings by Azan staining of posterolateral wall (A, x40), of local areas corresponding to BMCT (B, x100), and of old myocardial infarction (C, x100). Light microscopic findings by CD34 immunostaining of area of BMCT (D, x200), of old infarction (E, x200), and of control (nonischemic) anterior wall (F, x200).

 


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FIGURE 6. Histopathologic findings at autopsy: patient 3. Macroscopic finding of short-axial section of ventricles (A), light microscopic findings by elastica Masson staining of posterolateral wall where BMCT was performed (B, x40; D, x100), and light microscopic findings of old myocardial infarction where BMCT was not performed (C, x150). Proliferating vessels filled with red blood cells are shown by arrows in D.

 





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