Jiang Xin, Wang Yue-Fu, Zhao Qin-Hua, Jiang Rong, Wu Yan, Peng Fu-Hua, Xu Xi-Qi, Wang Lan, He Jing, Jing Zhi-Cheng
Thrombosis Medicine Center, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China.
Department of Anesthesiology, Fu Wai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China.
Int J Cardiol. 2014 Nov 15;177(1):61-5. doi: 10.1016/j.ijcard.2014.09.101. Epub 2014 Sep 28.
The Rho-kinase pathway has been shown to be involved in the pathogenesis of PAH. As yet, however, the acute effects of the Rho-kinase inhibitor fasudil have not been compared with established pulmonary selective vasodilators in patients with PAH. We compared the acute effects of intravenous fasudil with inhaled iloprost in patients with pulmonary arterial hypertension (PAH).
Using a crossover design, 50 patients with PAH (idiopathic PAH, PAH associated with repaired left-to-right cardiac shunts, or connective tissue disease) were randomized to iloprost inhalation (5 μg) and intravenous fasudil (30 mg over 30 min). Hemodynamic data were collected at baseline and during acute drug exposure.
Comparable decreases were observed in mean pulmonary artery pressure (-4.6 ± 4.3 mmHg vs. -4.8 ± 4.2 mmHg) and pulmonary vascular resistance (-3.0 ± 3.0 Wood U vs. -2.2 ± 2.7 Wood U) with fasudil infusion and iloprost inhalation, respectively, during acute challenge. However, fasudil infusion resulted in a more pronounced increase in mean cardiac output and mixed venous oxygen saturation compared with iloprost inhalation (13.7 ± 17.1% vs. 6.9 ± 15.0%; p=0.044 and 4.5 ± 5.3% vs. 2.7 ± 8.2%; p=0.044, respectively). Whereas inhaled iloprost resulted in a non-significant increase in mean systemic arterial oxygen saturation (0.8 ± 3.6%), infused fasudil resulted in a non-significant reduction (-0.6 ± 1.1%).
Infused fasudil improved pulmonary hemodynamics in patients with PAH without significant toxicity.
Rho激酶通路已被证明参与肺动脉高压（PAH）的发病机制。然而，迄今为止，Rho激酶抑制剂法舒地尔的急性效应尚未与PAH患者中已确立的肺选择性血管扩张剂进行比较。我们比较了静脉注射法舒地尔与吸入伊洛前列素对肺动脉高压（PAH）患者的急性效应。
采用交叉设计，将50例PAH患者（特发性PAH、与左向右心脏分流修复相关的PAH或结缔组织病）随机分为伊洛前列素吸入组（5μg）和静脉注射法舒地尔组（30mg，30分钟内）。在基线和急性药物暴露期间收集血流动力学数据。
在急性挑战期间，分别观察到法舒地尔输注和伊洛前列素吸入后平均肺动脉压（-4.6±4.3mmHg对-4.8±4.2mmHg）和肺血管阻力（-3.0±3.0伍德单位对-2.2±2.7伍德单位）有可比的下降。然而，与伊洛前列素吸入相比，法舒地尔输注导致平均心输出量和混合静脉血氧饱和度有更明显的增加（分别为13.7±17.1%对6.9±15.0%；p=0.044和4.5±5.3%对2.7±8.2%；p=0.044）。吸入伊洛前列素导致平均体循环动脉血氧饱和度有不显著的增加（0.8±3.6%），而输注法舒地尔导致有不显著的降低（-0.6±1.1%）。
输注法舒地尔可改善PAH患者的肺血流动力学，且无明显毒性。
