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.
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-HT(2A) 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.
Higashi
Yukihito
Y
Departments of Cardiovascular Physiology, Hiroshima University, Hiroshima, Japan. yhigashi@hiroshima-u.ac.jp
Miyazaki
Masanori
M
Goto
Chikara
C
Sanada
Hiroaki
H
Sueda
Taijiro
T
Chayama
Kazuaki
K
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods; D003131:Combined Modality Therapy; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D007866:Leg / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013386:Succinates / Q000494:pharmacology*; D014182:Transplantation, Autologous; D014665:Vasodilator Agents / Q000494:pharmacology
D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D013386:Succinates; D014665:Vasodilator Agents; D009599:Nitroprusside; C064294:sarpogrelate; D000109:Acetylcholine