Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia

• Published in: Circulation (New York, N.Y.) N.Y.), 2004-03, Vol.109 (10), p.1215-1218
• Main Authors: HIGASHI, Yukihito, KIMURA, Masashi, MATSUBARA, Hiroaki, MUROHARA, Toyoaki, YOSHIZUMI, Masao, HARA, Keiko, NOMA, Kensuke, JITSUIKI, Daisuke, NAKAGAWA, Keigo, OSHIMA, Tetsuya, CHAYAMA, Kazuaki, SUEDA, Taijiro, GOTO, Chikara
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Aged; Biological and medical sciences; Blood and lymphatic vessels; Bone Marrow Cells - physiology; Bone Marrow Transplantation; Cardiology. Vascular system; Collateral Circulation; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Female; Humans; Ischemia - etiology; Ischemia - physiopathology; Ischemia - therapy; Leg - blood supply; Male; Medical sciences; Middle Aged; Nitroprusside - pharmacology; Peripheral Vascular Diseases - complications; Plethysmography; Treatment Outcome; Vasodilator Agents - pharmacology
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000121427.53291.78

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. 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 1.6x10(9)+/-0.3x10(9). The number of CD34+ cells included in the implanted BM-MNCs was 3.8x10(7)+/-1.6x10(7). 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. These findings suggest that BM-MNC implantation augments endothelium-dependent vasodilation in patients with limb ischemia.