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Ann Thorac Surg 2003;75:768-773
© 2003 The Society of Thoracic Surgeons

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Original article: cardiovascular

Improvement of cardiac function by bone marrow cell implantation in a rat hypoperfusion heart model

^a Division of Cardiovascular Surgery, Department of Bioregulation, Yamaguchi University School of Medicine, Yamaguchi, Japan
^b Division of Cardiovascular Medicine, Department of Bioregulation, Yamaguchi University School of Medicine, Yamaguchi, Japan

Accepted for publication September 4, 2002.

^* Address reprint requests to Dr Hamano, Division of Cardiovascular Surgery, Department of Bioregulation, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
e-mail: kimikazu{at}yamaguchi-u.ac.jp

BACKGROUND: Local bone marrow cell implantation can induce angiogenesis. In the present study we investigated whether angiogenesis induced by bone marrow cell implantation improves deteriorated cardiac function in a rat heart model of hypoperfusion.

METHODS: A hypoperfusion heart model was created in Dark Agouti rats by ligating the left anterior descending artery placed against a copper wire (275 µm), then pulling out the wire immediately. The left ventricular (LV) anterior wall was injected directly at six points, each with 1 x 10⁷ bone marrow cells in 10 µL of phosphate-buffered saline or with phosphate-buffered saline only, respectively. Echocardiography was performed to evaluate the cardiac function 7, 30, 60, and 90 days after treatment. Microvessel density and blood flow in the LV anterior wall were estimated 60 days after treatment.

RESULTS: Both the increase of LV end-systolic diameter and the decrease of percent of fractional shortening caused by myocardial ischemia were attenuated effectively by bone marrow cell implantation treatment. Bone marrow cell implantation treatment also increased the levels of angiopoietin-1 and vascular endothelial growth factor in the LV anterior wall. The microvessel density, blood flow, and thickness of the LV anterior wall significantly also increased after bone marrow cell implantation treatment compared with those after phosphate-buffered saline injection.

CONCLUSIONS: The local implantation of autologous bone marrow cells induced angiogenesis and improved the perfusion of ischemic myocardium, thereby preventing LV remodeling and improving deteriorated cardiac function caused by myocardial hypoperfusion.

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