Efficacy of Rho kinase inhibitor fasudil in secondary Raynaud's phenomenon.
Efficacy of Rho kinase inhibitor fasudil in secondary Raynaud's phenomenon.
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DOI：
10.1002/acr.21622
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发表时间：
2012-06
影响因子：
4.7
通讯作者：
Boin, Francesco
中科院分区：
文献类型：
--
作者：
Fava, Andrea;Wung, Peter K.;Wigley, Fredrick M.;Hummers, Laura K.;Daya, Natalie R.;Ghazarian, Sharon R.;Boin, Francesco
RhoA/Rho激酶通路在冷诱导的血管收缩、血管平滑肌细胞功能和血管稳态中起着关键作用。本研究评价了法舒地尔（一种RhoA/Rho激酶抑制剂）逆转继发于系统性硬化症（SSc）的雷诺现象（RP）患者冷诱导血管痉挛的疗效。这是一项单中心、双盲、安慰剂对照、随机化、3阶段交叉研究，在标准化寒冷激发前2小时口服法舒地尔（40 mg或80 mg）或安慰剂。冷刺激后皮肤温度的下降以及恢复50%和70%刺激前手指皮肤温度的时间被用作主要结局。还测量了通过激光多普勒评估的指血流、达到最低皮肤温度的时间和皮肤冷却速率。17例SSc和RP患者完成了研究。冷刺激后，皮肤温度和平均时间（分钟）恢复50%（安慰剂：7.9，法舒地尔40 mg：7.5，法舒地尔80 mg：8.2; p=.791）和70%（安慰剂：18.2，法舒地尔40 mg：15.0，法舒地尔80 mg：17.1; p= 0.654）三组之间激发前皮肤温度无显著差异。法舒地尔治疗组的指血流测量值高于安慰剂组，但差异不显著（p= 0.693）。单次口服法舒地尔40 mg或80 mg在低温刺激后的皮肤温度恢复时间和手指血流量方面没有显著获益。
The RhoA/Rho-kinase pathway plays a pivotal role in cold induced vasoconstriction, vascular smooth muscle cells function and vascular homeostasis. This study evaluates the efficacy of fasudil, a RhoA/Rho-kinase inhibitor, to reverse cold-induced vasospasm in patients with Raynaud’s phenomenon (RP) secondary to systemic sclerosis (SSc). This is a single-center, double-blind, placebo-controlled, randomized, 3-period crossover study of oral fasudil (40 mg or 80 mg) or placebo administered 2 hours before a standardized cold challenge. The fall in skin temperature after the cold challenge and time to recover 50% and 70% of pre-challenge digital skin temperature were used as primary outcomes. Digital blood flow assessed by Laser Doppler, time to minimum skin temperature, and rate of skin cooling were also measured. Seventeen patients with SSc and RP completed the study. After cold challenge, skin temperatures and the average time (minutes) to recover 50% (placebo: 7.9, fasudil 40 mg: 7.5, and fasudil 80 mg: 8.2; p=.791) and 70% (placebo: 18.2, fasudil 40 mg: 15.0, and fasudil 80 mg: 17.1; p=.654) of pre-challenge skin temperature were not significantly different across the three groups. The digital blood flow measurements were higher in fasudil treated groups than placebo but differences were not significant (p=.693). Fasudil administered at single oral dose of 40 mg or 80 mg was not associated with significant benefit in term of skin temperature recovery time and digital blood flow after cold challenge.
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DOI：
10.1152/ajpheart.2000.278.4.h1075
发表时间：
2000-04-01
影响因子：
4.8
作者：
Chotani, MA;Flavahan, S;Flavahan, NA
通讯作者：
Flavahan, NA
影响因子：
2.9
作者：
WOLLERSHEIM, H;THIEN, T;VANTLAAR, A
通讯作者：
VANTLAAR, A
影响因子：
24
作者：
Yada, T;Shimokawa, H;Kajiya, F
通讯作者：
Kajiya, F
影响因子：
2.9
作者：
Hinderling, Peter H.;Karara, Adel H.;Lu, Ming
通讯作者：
Lu, Ming
影响因子：
--
作者：
Wise, RA;Wigley, FA;Czerwiec, FS
通讯作者：
Czerwiec, FS