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A novel application of myocardial contrast echocardiography to evaluate angiogenesis by autologous bone marrow cell transplantation in chronic ischemic pig model

Hiroko Fujii, MD, PhD^*, Shinji Tomita, MD, PhD^*,2, Takeshi Nakatani, MD, PhD, Shinya Fukuhara, MD^||, Akihisa Hanatani, MD, PhD, Yoshinori Ohtsu, MD^*, Michiko Ishida, MD, Chikao Yutani, MD, PhD^||, Kunio Miyatake, MD, PhD, FACC and Soichiro Kitamura, MD, PhD, FACC^,1

^* Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center, Osaka, Japan
Department of Cardiovascular Medicine, National Cardiovascular Center, Osaka, Japan
Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan
Department of Organ Transplantation, National Cardiovascular Center, Osaka, Japan
^|| Department of Pathology, National Cardiovascular Center, Osaka, Japan

View larger version (94K): [in a new window]   Figure 1 Capillary formation at the anteroseptum and anterior wall. Number 1 represents the bone marrow mononuclear cell (BMMNC) subset; number 2 represents the bone marrow stromal cell (BMSC) subset; and number 3 represents the control group (magnification x200). The top row (1a, 2a, 3a) shows the findings of the anteroseptum (nontransplanted infarct area), and bottom row (1b, 2b, 3b) shows the findings of the anterior wall (transplanted infarct area). In the BMMNC and BMSC subsets, the anterior wall (1b, 2b) contained more capillaries than the anteroseptum (1a, 2a). In contrast, in the control group, both the anteroseptum (3a) and anterior wall (3b) contained very few capillaries.

View larger version (14K): [in a new window]   Figure 2 The capillary density (CD) of the anteroseptum (open bars) and anterior wall (solid bars). The CD of the anterior wall was higher than that of the anteroseptum in the cell transplant group (**p = 0.0081; A) (*p = 0.025 and *p = 0.025 for bone marrow mononuclear cell (BMMNC) and bone marrow stromal cell (BMSC) subsets, respectively; B), although there was no difference between the two areas in the control group (A).

View larger version (50K): [in a new window]   Figure 3 The myocardial contrast intensity (MCI) of the bone marrow mononuclear cell subset at one month after cell transplantation. The four graphs enable us to quantify MCI and to recognize the differences in the anteroseptum, anterior wall, septum, and lateral wall. The MCI in the anterior wall was higher than that in the anteroseptum.

View larger version (13K): [in a new window]   Figure 4 Relationship between myocardial contrast intensity (MCI) and capillary density (CD). (A) When MCI was evaluated by dB, a logarithmic relation was seen between MCI and CD. (B) When MCI was evaluated by AU2, a linear relation was seen between them.

View larger version (12K): [in a new window]   Figure 5 Time course of myocardial contrast intensity (MCI) in the anteroseptum and anterior wall before and after transplantation. The straight line indicates the cell transplant group (bone marrow mononuclear cell and bone marrow stromal cell subsets), and the dashed line indicates the control group. (A) At the anteroseptum (nontransplanted infarct area), there was no significant change between the groups or stages. (B) At the anterior wall (transplanted infarct area), the MCI of the cell transplant group significantly increased after transplantation (*p = 0.018), although that of the control group did not change.