Sarpogrelate Hydrochloride, a Selective 5-HT2A Antagonist, Augments Autologous Bone-Marrow Mononuclear Cell Implantation-induced Improvement in Endothelium-Dependent Vasodilation in Patients with Critical Limb Ischemia Brief title: Cell therapy, 5-HT2A antagonist and endothelial function

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 and sodium nitroprusside (SNP) before and after BM-MNC implantation in 16 patients with CLI. We divided CLI patients into two groups: those co-treated 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, transcutanous oxygen pressure, and pain-free walking time. There was no significant difference in these parameters between the two groups. Before BM-MNC implantation, LBF responses to acetylcholine were similar in the sarpogrelate group and control group. Twelve weeks of BM-MNC implantation enhanced LBF responses to acetylcholine in the sarpogrelate and control groups. After 12 weeks of BM-MNC implantation, LBF response to acetylcholine was significantly greater in the sarpogrelate group than in the control group. BM-MNC implantation did not alter the LBF responses to SNP in either group. Conclusion: 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.