Li Fuhai, Xia Wei, Yuan Shuanghu, Sun Ruopeng
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, China.
Pediatr Cardiol. 2009 Apr;30(3):363-6. doi: 10.1007/s00246-008-9315-z. Epub 2008 Oct 25.
This study aimed to determine whether the Rho-kinase-mediated pathway is involved in the pathogenesis of left-to-right shunt-induced pulmonary hypertension and whether fasudil exhibits acute beneficial effects on the hemodynamics of these patients. A total of 12 patients with a mean age of 12.3 years were enrolled in a self-controlled prospective study. All the patients had a diagnosis of congenital heart disease with slight to moderate pulmonary hypertension and were scheduled for transcatheter closure. After placement of the catheters, 30 mg/kg fasudil was injected intravenously over 30 min under room air conditions. Hemodynamic parameters including pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), systemic artery pressure (SAP), systemic vascular resistance (SVR), cardiac input, and blood oxygen saturation were measured and calculated at baseline and 30 min after fasudil injection. After fasudil treatment, PASP decreased to a level 33.03 +/- 6.64% less than baseline value (p < 0.01), and maximal PVR decreased to a level 33.03 +/- 6.64% less than baseline value (p < 0.01). Cardiac input increased to a level 7.7 +/- 5.2% more than baseline value (p < 0.05), and mixed venous oxygen saturation significantly increased to a level 7.7 +/- 5.2% more than baseline value (p < 0.01). The left-to-right shunt ratio (Q(P)/Q(S)) also tended to increase (16.2 +/- 12.5% of baseline value; p < 0.01). Whereas SAP showed only a slight decrease (-1.6 +/- 3.1% of baseline value; p = 0.08), SVR significantly decreased (-10.2 +/- 12.2% of baseline value; p < 0.01), and the PVR/SVR ratio tended to decrease (-23.9 +/- 15.1% of baseline value). In conclusion, Rho-kinase is involved in the pathogenesis of left-to-right shunt-induced pulmonary hypertension, and fasudil is a novel therapeutic approach.
本研究旨在确定Rho激酶介导的通路是否参与左向右分流所致肺动脉高压的发病机制，以及法舒地尔对这些患者的血流动力学是否具有急性有益作用。共有12例平均年龄为12.3岁的患者纳入一项自身对照前瞻性研究。所有患者均诊断为先天性心脏病合并轻度至中度肺动脉高压，并计划行导管封堵术。放置导管后，在室内空气条件下于30分钟内静脉注射30mg/kg法舒地尔。在基线及法舒地尔注射后30分钟测量并计算血流动力学参数，包括肺动脉收缩压（PASP）、肺血管阻力（PVR）、体动脉压（SAP）、体循环血管阻力（SVR）、心输出量和血氧饱和度。法舒地尔治疗后，PASP降至比基线值低33.03±6.64%的水平（p<0.01），最大PVR降至比基线值低33.03±6.64%的水平（p<0.01）。心输出量增加至比基线值高7.7±5.2%的水平（p<0.05），混合静脉血氧饱和度显著增加至比基线值高7.7±5.2%的水平（p<0.01）。左向右分流率（Q(P)/Q(S)）也趋于增加（为基线值的16.2±12.5%；p<0.01）。虽然SAP仅略有下降（为基线值的-1.6±3.1%；p = 0.08），但SVR显著下降（为基线值的-10.2±12.2%；p<0.01），且PVR/SVR比值趋于下降（为基线值的-23.9±15.1%）。总之，Rho激酶参与左向右分流所致肺动脉高压的发病机制，法舒地尔是一种新的治疗方法。
