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J Am Coll Cardiol, 2004; 43:1299-1305, doi:10.1016/j.jacc.2003.09.061
© 2004 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: PRECLINICAL STUDY

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*{dagger}, Shinji Tomita, MD, PhD*{ddagger},2, Takeshi Nakatani, MD, PhD§, Shinya Fukuhara, MD||, Akihisa Hanatani, MD, PhD{dagger}, Yoshinori Ohtsu, MD*, Michiko Ishida, MD{dagger}, Chikao Yutani, MD, PhD||, Kunio Miyatake, MD, PhD, FACC{dagger} and Soichiro Kitamura, MD, PhD, FACC{ddagger},1

* Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center, Osaka, Japan
{dagger} Department of Cardiovascular Medicine, National Cardiovascular Center, Osaka, Japan
{ddagger} 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

Manuscript received July 11, 2003; revised manuscript received September 1, 2003, accepted September 16, 2003.

2 Correspondence: Dr. Shinji Tomita, Cardiothoracic Surgical Unit, Auckland City Hospital, Private Bag 92024, Auckland, New Zealand.
shinjitomita{at}hotmail.com

1 Reprint requests: Dr. Soichiro Kitamura, President of National Cardiovascular Center, Chairman of Department of Cardiovascular Surgery, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565 Japan.
skitamura{at}hsp.ncvc.go.jp

OBJECTIVES: We investigated the feasibility of myocardial contrast echocardiography (MCE) to evaluate regional perfusion after bone marrow cell transplantation.

BACKGROUND: The myocardial microvessels improved by cell transplantation are too small to visualize with conventional angiography.

METHODS: Fourteen mini-pigs from the Nippon Institute for Biological Science were used. The proximal left anterior descending coronary artery was ligated. One month later, nine pigs survived. Six pigs received autologous cell transplantation into the left ventricular anterior wall: bone marrow mononuclear cells (BMMNCs) (n = 3) and bone marrow stromal cells (BMSCs) (n = 3). The other three pigs received saline (control group, n = 3). The pigs were sacrificed one month later. Myocardial contrast intensity (MCI) with a contrast agent was measured using the SONOS 5500 system (Philips). Capillary density (CD) and MCI were measured at four areas: anteroseptum (nontransplanted infarct area), anterior wall (transplanted infarct area), septum (border zone), and lateral wall (normal). We compared the anteroseptum with the anterior wall by MCI and CD.

RESULTS: In the BMMNC and BMSC subsets, the CD of the anterior wall was higher than that of the anteroseptum (p < 0.001). There was a linear relation between MCI and CD (acoustic unit [AU2] = 0.234 CD + 0.010, r = 0.92, p < 0.001). At one month after cell transplantation, MCI of the anterior wall increased in the BMMNC and BMSC subsets (p < 0.05), although it did not change in the control group. The ratio of wall thickness (systole/diastole) in the transplanted infarct area was larger than that in the nontransplanted infarct area (p < 0.01).

CONCLUSIONS: Myocardial contrast echocardiography is useful to evaluate regional perfusion, which was enhanced by bone marrow cell transplantation.

Abbreviations and Acronyms
  AU = acoustic unit
  BMMNC = bone marrow mononuclear cell
  BMSC = bone marrow stromal cell
  CD = capillary density
  MCE = myocardial contrast echocardiography
  MCI = myocardial contrast intensity
  MI = myocardial infarction




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