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


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 1.6x10(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.


CONCLUSIONS
These findings suggest that BM-MNC implantation augments endothelium-dependent vasodilation in patients with limb ischemia.
Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. yhigashi@hiroshima-u.ac.jp
Yukihito
Y
Higashi
Masashi
M
Kimura
Keiko
K
Hara
Kensuke
K
Noma
Daisuke
D
Jitsuiki
Keigo
K
Nakagawa
Tetsuya
T
Oshima
Kazuaki
K
Chayama
Taijiro
T
Sueda
Chikara
C
Goto
Hiroaki
H
Matsubara
Toyoaki
T
Murohara
Masao
M
Yoshizumi
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D003097:Collateral Circulation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007511:Ischemia / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D016491:Peripheral Vascular Diseases / Q000150:complications*; D010991:Plethysmography; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine