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(Circulation. 2004;109:1215-1218.)
© 2004 American Heart Association, Inc.

Brief Rapid Communications

Autologous Bone-Marrow Mononuclear Cell Implantation Improves Endothelium-Dependent Vasodilation in Patients With Limb Ischemia

Yukihito Higashi, MD; Masashi Kimura, MD; Keiko Hara, MD; Kensuke Noma, MD; Daisuke Jitsuiki, MD; Keigo Nakagawa, MD; Tetsuya Oshima, MD; Kazuaki Chayama, MD; Taijiro Sueda, MD; Chikara Goto, RTP, MS; Hiroaki Matsubara, MD; Toyoaki Murohara, MD; Masao Yoshizumi, MD

From the Department of Cardiovascular Physiology and Medicine (Y.H., M.Y.), Department of Medicine and Molecular Science (M.K., K.H., K. Noma, D.J., K. Nakagawa, K.C.), Division of Physical Therapy, Institute of Health Sciences (C.G.), and the Department of Clinical Laboratory Medicine (T.O.), Department of Surgery (T.S.), Hiroshima University Graduate School of Biomedical Sciences, Department of Cardiovascular Medicine (H.M.), Kyoto Prefectural University of Medicine, and Department of Cardiology (T.M.), Nagoya University Graduate School of Medicine.

Correspondence to Yukihito Higashi, MD, PhD, FAHA, Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail yhigashi{at}hiroshima-u.ac.jp

Received March 5, 2003; de novo received December 15, 2003; revision received January 28, 2003; accepted January 28, 2003.

Background— Patients with limb ischemia were associated with endothelial dysfunction. The purpose of this study was to determine whether autologous bone-marrow mononuclear cell (BM-MNC) implantation improves endothelial dysfunction in patients with limb ischemia.

Methods and Results— We evaluated the leg blood flow (LBF) response to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, before and after BM-MNC implantation in 7 patients with limb ischemia. LBF was measured with a mercury-filled Silastic strain-gauge plethysmograph. The number of BM-MNCs implanted into ischemic limbs was 1.6x10⁹±0.3x10⁹. The number of CD34⁺ cells included in the implanted BM-MNCs was 3.8x10⁷±1.6x10⁷. BM-MNC implantation improved the ankle-brachial pressure index (0.33±0.21 to 0.39±0.17, P=0.06), transcutaneous oxygen pressure (28.4±11.5 to 36.6±5.2 mm Hg, P=0.03), and pain-free walking time (0.8±0.6 to 2.9±2.2 minutes, P=0.02). After BM-MNC implantation, LBF response to ACh was enhanced (19.3±6.8 versus 29.6±7.1 mL/min per 100 mL; P=0.002). The vasodilatory effect of SNP was similar before and after BM-MNC implantation.

Conclusions— These findings suggest that BM-MNC implantation augments endothelium-dependent vasodilation in patients with limb ischemia.

Key Words: angiogenesis • cells • endothelium • ischemia

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