Premilinary Observation of Sarpogrelate Hydrochloride on Prevention and Treatment for Gluteal and Limb Ischemia Following Endovascular Repair of Abdominal Aortic Aneurysm_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HUANG Bin ,  ZHAO Jichun , MA Yukui , LU Wusheng , YANG Yi , YUAN Ding.

The Center of Vascular Surgery and Endovascular Therapy， West China Hospital， Sichuan University， Chengdu 610041， Sichuan Province， China;

Corresponding author：

ZHAO Jichun, Email: zhaojc3@126.com

Keywords：

Abdominal aortic aneurysm; Endovascular repair; Sarpogrelate hydrochloride

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Objective 　To observe the effects of sarpogrelate hydrochloride in prevention and treatment for ischemia of gluteal and limb following endovascular repair of abdominal aortic aneurysm （EVAR）.
Methods 　Clinical data were analyzed in 174 patients with abdominal aortic aneurysm （AAA） who underwent EVAR from January 2006 to January 2011. The patients’ mean age was （71.8±8.2）years old （male： 148 cases， female： 26 cases）. The diameter of abdominal aortic aneurysm was （55.2±12.9） mm. AAA involving common iliac artery was in 52 （29.9%） patients. Bifurcated endografts and aorto-uni-iliac （AUI） endografts with crossover bypass were used in 169 patients （97.1%） and 5 patients （2.9%）， respectively. Sarpogrelate hydrochloride were used in 39 patients with gluteal and limb ischemia due to exclusion of bilateral and unilateral internal iliac arteries among 174 patients. Sarpogrelate hydrochloride， 100 mg， three times daily，was taken for 2-4 weeks. Symptoms of gluteal and limb ischemia were followed-up.
Results 　All of patients with AAA was repaired by EVAR successfully and no conversion to open repair. General anesthesia 〔50.6%（88/174）〕， epidural anesthesia 〔30.0%（52/174）〕， and local anesthesia 〔19.5%（34/174）〕 were used. Blood loss was （125.2±43.1） ml and no blood transfusion during operation. Operative time was （145.5±38.7） min, ICU stay time was （14.7±5.2） h， and postoperative fasting time was （7.2±4.3） h. The duration of postoperative hospital stay was （9.1±2.7） d. The perioperative complication rate was 12.6% （22/174）. The 30-day mortality rate was 1.1% （2/174）. Gluteal and limb claudication occurred in 2 paients and 5 patients respectively among 29 patients with EVAR due to exclusion of unilateral internal iliac artery， intermittent claudication distance was 100-200 meters. Gluteal muscle pain and limb claudication for less than 200 meters occurred in 4 patients due to exclusion of bilateral internal iliac artery. The symptoms were relieved after Sarpogrelate hydrochloride， 100 mg， three times daily， was taken for 2-4 weeks. No gluteal gangrene occurred and claudication distances were more than 500 meters when walking， no any interventional and surgical procedures were required， all of them were doing well for median 16.1 months follow-up period.
Conclusions 　Sarpogrelate hydrochloride has definite effects on prevention and treatment for gluteal and limb ischemia following endovascular repair of abdominal aortic aneurysm，especially for exclusion of bilateral and unilateral internal iliac arteries during EVAR

Citation： HUANG Bin,ZHAO Jichun,MA Yukui,LU Wusheng,YANG Yi,YUAN Ding.. Premilinary Observation of Sarpogrelate Hydrochloride on Prevention and Treatment for Gluteal and Limb Ischemia Following Endovascular Repair of Abdominal Aortic Aneurysm. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(1): 82-86. doi: Copy

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2.	Heller JA， Weinberg A， Arons R， et al. Two decades of abdominal aortic aneurysm repair： have we made any progress [J]. J Vasc Surg， 2000， 32(6)： 1091-1100.
3.	Parodi JC， Palmaz JC， Barone HD. Transfemoral intraluminal graft implantation for abdominal aortic aneurysms [J]. Ann Vasc Surg，1991， 5(6)： 491-499.
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7.	Bratby MJ， Munneke GM， Belli AM， et al. How safe is bilateral internal iliac artery embolization prior to EVAR [J]. Cardiovasc Intervent Radiol， 2008， 31(2)： 246-253.
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11.	Maleux G， Koolen M， Heye S， et al. Limb occlusion after endovascular repair of abdominal aortic aneurysms with supported endografts [J]. J Vasc Interv Radiol，2008， 19(10)： 1409- 1412.
12.	Higashi Y， Miyazaki M， Goto C， et al. 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 [J]. J Cardiovasc Pharmacol， 2010，55(1)： 56-61.
13.	Houkin K， Nakayama N， Nonaka T， et al. The 5-hydroxytryptamine 2A receptor antagonist sarpogrelate hydrochloride inhibits acute platelet aggregation in injured endothelium [J]. J Int Med Res， 2006， 34(1)： 65-72.
14.	Shikata C， Nemoto M， Ebisawa T， et al. Effect of sarpogrelate on cardiovascular disorders [J]. Exp Clin Cardiol， 2011，16(3)： 75-76.
15.	Kajiwara I， Soejima H， Miyamoto S， et al. Effects of additional treatment of sarpogrelate to aspirin therapy on platelet aggregation and plasma plasminogen activator inhibitor activity in patients with stable effort angina [J]. Thromb Res， 2011，128(6)：547-551.
16.	Choi J， Kermode JC. New therapeutic approaches to combat arterial thrombosis： better drugs for old targets， novel targets， and future prospects[ J]. Mol Interv， 2011，11(2)： 111-123.
17.	Nakamura E， Tanaka N， Kuwabara M， et al. Relative contribu中国普外基础与临床杂志2012 年1 月第19 卷第1 期 Chin J Bases ? 86 ? Clin General Surg, Vol. 19, No. 1, Jan. 2012tions of 5-hydroxytryptamine (5-HT) receptor subtypes in 5-HTinduced vasoconstriction of the distended human saphenous vein as a coronary artery bypass graft [J]. Biol Pharm Bull， 2011，34(1)： 82-86.
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20.	Sun YM， Su Y， Jin HB， et al. Sarpogrelate protects against high glucose-induced endothelial dysfunction and oxidative stress [J]. Int J Cardiol，2011， 147(3)： 383-387.
21.	Hiroshi M，Hiroshi S. Effects of the 5-HT2A antagonist sarpogrelate on walking ability in patients with intermittent claudication as measured using the walking impairment questionnaire [J]. Ann Vasc Dis， 2008， 1 (2)：102-110.
22.	Kodama A， Komori K， Kajikuri J， et al. Chronic treatment of hydroxytryptamine type 2a receptor antagonist sarpogrelate hydrochloride modulates the vasoreactivity of serotonin in experimental rabbit vein grafts [J]. J Vasc Surg， 2009， 50(3)： 617-625.[ 23] Kodama A， Komori K， Hattori K， et al. Sarpogrelate hydrochloride reduced intimal hyperplasia in experimental rabbit vein graft [J]. J Vasc Surg， 2009，49(5)： 1272-1281.
23.	Nishihira K， Yamashita A， Tanaka N， et al. Serotonin induces vasoconstriction of smooth muscle cell-rich neointima through 5-hydroxytryptamine 2A receptor in rabbit femoral arteries [J].J Thromb Haemost， 2008， 6(7)： 1207-1214.
24.	Bir SC， Fujita M， Marui A， et al. New therapeutic approach for impaired arteriogenesis in diabetic mouse hindlimb ischemia[J]. Circ J， 2008， 72(4)： 633-640.[ 26] Shimizu T，Yamada Y，Tashita A，et al. Pharmacokinetic analysis of antiplatelet effect of sarpogrelate hydrochloride and its application to drug dosage regimen－ modeling based on reversible inhibition of 5-HT2 serotonergic receptor in the platelet membrane by sarpogrelate hydrochloride and its metabolite [J].Yakugaku Zasshi， 1999，19(11)：850-860.

1. Baril DT， Kahn RA， Ellozy SH， et al. Endovascular abdominal aortic aneurysm repair： emerging developments and anesthetic considerations [J]. J Cardiothorac Vasc Anesth， 2007， 21(5)：730-742.
2. Heller JA， Weinberg A， Arons R， et al. Two decades of abdominal aortic aneurysm repair： have we made any progress [J]. J Vasc Surg， 2000， 32(6)： 1091-1100.
3. Parodi JC， Palmaz JC， Barone HD. Transfemoral intraluminal graft implantation for abdominal aortic aneurysms [J]. Ann Vasc Surg，1991， 5(6)： 491-499.
4. Cochennec F， Marzelle J， Allaire E， et al. Open vs. endovascular repair of abdominal aortic aneurysm involving the iliac bifurcation [J]. J Vasc Surg，2010，51(6)： 1360-1366.
5. Zander T， Baldi S， Rabellino M， et al. Bilateral hypogastric artery occlusion in endovascular repair of abdominal aortic aneurysms and its clinical significance [J]. J Vasc Interv Radiol，2007， 18(12)： 1481-1486.
6. Libicher M， Pavlidis D， Bangard C， et al. Occlusion of the internal iliac artery prior EVAR： comparison of coils and plugs [J]. Vasc Endovascular Surg， 2011， Dec 14.[ Epub ahead of print].
7. Bratby MJ， Munneke GM， Belli AM， et al. How safe is bilateral internal iliac artery embolization prior to EVAR [J]. Cardiovasc Intervent Radiol， 2008， 31(2)： 246-253.
8. Hosaka A， Kato M， Kato I， et al. Outcome after concomitant unilateral embolization of the internal iliac artery and contralateral external-to-internal iliac artery bypass grafting during endovascular aneurysm repair [J]. J Vasc Surg， 2011， 54(4)： 960-964.
9. Maleux G， Willems E， Vaninbroukx J， et al. Outcome of proximal internal iliac artery coil embolization prior to stent-graft extension in patients previously treated by endovascular aortic repair [J]. J Vasc Interv Radiol， 2010， 21(7)： 990-994.
10. Maldonado TS， Rockman CB， Riles E， et al. Ischemic complications after endovascular abdominal aortic aneurysm repair [J]. J Vasc Surg，2004，40(4)： 703-709，710.
11. Maleux G， Koolen M， Heye S， et al. Limb occlusion after endovascular repair of abdominal aortic aneurysms with supported endografts [J]. J Vasc Interv Radiol，2008， 19(10)： 1409- 1412.
12. Higashi Y， Miyazaki M， Goto C， et al. 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 [J]. J Cardiovasc Pharmacol， 2010，55(1)： 56-61.
13. Houkin K， Nakayama N， Nonaka T， et al. The 5-hydroxytryptamine 2A receptor antagonist sarpogrelate hydrochloride inhibits acute platelet aggregation in injured endothelium [J]. J Int Med Res， 2006， 34(1)： 65-72.
14. Shikata C， Nemoto M， Ebisawa T， et al. Effect of sarpogrelate on cardiovascular disorders [J]. Exp Clin Cardiol， 2011，16(3)： 75-76.
15. Kajiwara I， Soejima H， Miyamoto S， et al. Effects of additional treatment of sarpogrelate to aspirin therapy on platelet aggregation and plasma plasminogen activator inhibitor activity in patients with stable effort angina [J]. Thromb Res， 2011，128(6)：547-551.
16. Choi J， Kermode JC. New therapeutic approaches to combat arterial thrombosis： better drugs for old targets， novel targets， and future prospects[ J]. Mol Interv， 2011，11(2)： 111-123.
17. Nakamura E， Tanaka N， Kuwabara M， et al. Relative contribu中国普外基础与临床杂志2012 年1 月第19 卷第1 期 Chin J Bases ? 86 ? Clin General Surg, Vol. 19, No. 1, Jan. 2012tions of 5-hydroxytryptamine (5-HT) receptor subtypes in 5-HTinduced vasoconstriction of the distended human saphenous vein as a coronary artery bypass graft [J]. Biol Pharm Bull， 2011，34(1)： 82-86.
18. Horiuchi M， Okita K， Takada S， et al. Effects of oral singledose administration of sarpogrelate hydrochloride on saturation O2 of calf muscle during plantar flexion exercise [J]. Adv Exp Med Biol， 2010， 662： 531-536.
19. Kim KM， Kim H， Chi HS， et al. Comparison of antiplatelet potency of sarpogrelate， aspirin， and beraprost in healthy volunteers according to in vitro closure time [J]. Blood Coagul Fibrinolysis， 2010，21(3)：262-265.
20. Sun YM， Su Y， Jin HB， et al. Sarpogrelate protects against high glucose-induced endothelial dysfunction and oxidative stress [J]. Int J Cardiol，2011， 147(3)： 383-387.
21. Hiroshi M，Hiroshi S. Effects of the 5-HT2A antagonist sarpogrelate on walking ability in patients with intermittent claudication as measured using the walking impairment questionnaire [J]. Ann Vasc Dis， 2008， 1 (2)：102-110.
22. Kodama A， Komori K， Kajikuri J， et al. Chronic treatment of hydroxytryptamine type 2a receptor antagonist sarpogrelate hydrochloride modulates the vasoreactivity of serotonin in experimental rabbit vein grafts [J]. J Vasc Surg， 2009， 50(3)： 617-625.[ 23] Kodama A， Komori K， Hattori K， et al. Sarpogrelate hydrochloride reduced intimal hyperplasia in experimental rabbit vein graft [J]. J Vasc Surg， 2009，49(5)： 1272-1281.
23. Nishihira K， Yamashita A， Tanaka N， et al. Serotonin induces vasoconstriction of smooth muscle cell-rich neointima through 5-hydroxytryptamine 2A receptor in rabbit femoral arteries [J].J Thromb Haemost， 2008， 6(7)： 1207-1214.
24. Bir SC， Fujita M， Marui A， et al. New therapeutic approach for impaired arteriogenesis in diabetic mouse hindlimb ischemia[J]. Circ J， 2008， 72(4)： 633-640.[ 26] Shimizu T，Yamada Y，Tashita A，et al. Pharmacokinetic analysis of antiplatelet effect of sarpogrelate hydrochloride and its application to drug dosage regimen－ modeling based on reversible inhibition of 5-HT2 serotonergic receptor in the platelet membrane by sarpogrelate hydrochloride and its metabolite [J].Yakugaku Zasshi， 1999，19(11)：850-860.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Premilinary Observation of Sarpogrelate Hydrochloride on Prevention and Treatment for Gluteal and Limb Ischemia Following Endovascular Repair of Abdominal Aortic Aneurysm

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