Sarpogrelate Hydrochloride, a Selective 5-hydroxytryptamine(2A) Antagonist, Augments Autologous Bone Marrow Mononuclear Cell Implantation-induced Improvement in Endothelium-dependent Vasodilation in Patients With Critical Limb Ischemia

Higashi Yukihito

Miyazaki Masanori

Goto Chikara

Sanada Hiroaki

Sueda Taijiro

Chayama Kazuaki

Journal of Cardiovascular Pharmacology

Background: The purpose of this study was to determine the effect of a combination of bone marrow mononuclear cell (BM-MNC) implantation and sarpogrelate, a selective 5-HT2A antagonist, on endothelial function in patients with critical limb ischemia (CLI). Methods: We evaluated the leg blood flow (LBF) responses to acetylcholine (ACh) and sodium nitroprusside before and after BM-MNC implantation in 16 patients with CLI. We divided patients with CLI into 2 groups: those cotreated with sarpogrelate orally for 12 weeks (sarpogrelate group, n = 8) and those who remained on conventional therapy (control group, n = 8). LBF was measured by strain gauge plethysmography. Results: BM-MNC implantation improved ankle brachial pressure index, transcutaneous oxygen pressure, and pain-free walking time, There was no significant difference in these parameters between the 2 groups. Before BM-MNC implantation, LBF responses to ACh were similar in the sarpogrelate group and control group. Twelve weeks of BM-MNC implantation enhanced LBF responses to ACh in the sarpogrelate and control groups. After 12 weeks of BM-MNC implantation, LBF response to ACh was significantly greater in the sarpogrelate group than in the control group. BM-MNC implantation did not alter the LBF responses to sodium nitroprusside in either group. Conclusions: These findings suggest that BM-MNC implantation improved not only limb ischemic symptoms but also endothelium-dependent vasodilation in patients with CLI. A combination of BM-MNC implantation and sarpogrelate had a more beneficial effect on vascular function in these patients.

angiogenesis

cell therapy

endothelial function

limb ischemia

Medical sciences [ 490 ]

eng

Lippincott Williams & Wilkins

Copyright (c) 2010 Lippincott Williams & Wilkins, Inc.

[ISSN] 0160-2446

[DOI] 10.1097/FJC.0b013e3181c37da4

[NCID] AA00257104

[DOI] http://dx.doi.org/10.1097/FJC.0b013e3181c37da4