Hsieh Min-Ling, Liu Ping-Yen, Wu Jing-Ming, Liao James K, Wang Jieh-Neng
Departments of Pediatrics;
Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; ; Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan;
Acta Cardiol Sin. 2015 Nov;31(6):494-9. doi: 10.6515/acs20150424d.
Patent ductus arteriosus (PDA) causes increased pulmonary blood flow, which can lead to pulmonary arterial hypertension (PAH). Rho-associated coiled-coil containing protein kinase (ROCK) may play an important pathophysiological role in PAH. We hypothesized that the increased pulmonary artery (PA) flow from PDA could activate ROCK.
Patients who received a PDA transcatheter closure in our hospital were consecutively enrolled in this study. Basic demographics and clinical hemodynamic data of the study participants were recorded. Then, ROCK activity was measured before and after the PDA occlusion procedure. ROCK activity was defined as the phosphorylation ratio of myosin-binding subunit by Western blot measurement. We also sub-divided patients into the coil group and occluder group based on the occlusion device used in each patient's procedure.
From January 2009 to December 2011, 25 patients with a median age of 2.3 years, ranging from 10 months to 72 years were enrolled. The mean PDA size was 0.31 ± 0.14 cm, the mean Qp/Qs shunt was 1.54 ± 0.41, and the mean systolic pulmonary artery pressure was 26.9 ± 10.3 mmHg. There were 10 patients (one boy and nine girls) in the coil group and 15 patients (four boys and eleven girls) in the occluder group. Following the closure of the PDA, ROCK activity significantly decreased (1.78 ± 2.25 vs. 0.77 ± 0.69, p < 0.01). There was a strong correlation between the leukocyte ROCK activity with the systolic PA pressure (y = 5.4608x + 22.54, R2 = 0.5539, p < 0.05), but not the Qp/Qs value. Both subgroups showed significant changes of ROCK activity after the procedure. Interestingly, when comparing the coil group with the occluder group, the decrease in ROCK activity was more apparent in the occluder group.
The findings of this study indicated that ROCK activity is higher in patients with PDA and correlates with PA pressure. The decrease in ROCK activity following the device closure suggests that ROCK may be an important biomarker for PDA patency.
Patent ductus arteriosus (PDA); Pulmonary arterial pressure; Rho kinase; Transcatheter closure.
动脉导管未闭（PDA）会导致肺血流量增加，进而可能引发肺动脉高压（PAH）。含 Rho 相关卷曲螺旋的蛋白激酶（ROCK）可能在 PAH 的病理生理过程中发挥重要作用。我们推测，PDA 导致的肺动脉（PA）血流增加可能会激活 ROCK。
连续纳入在我院接受 PDA 经导管封堵术的患者。记录研究参与者的基本人口统计学和临床血流动力学数据。然后，在 PDA 封堵术前和术后测量 ROCK 活性。通过蛋白质印迹法将 ROCK 活性定义为肌球蛋白结合亚基的磷酸化比率。我们还根据每位患者手术中使用的封堵装置将患者分为线圈组和封堵器组。
2009 年 1 月至 2011 年 12 月，共纳入 25 例患者，中位年龄 2.3 岁，年龄范围为 10 个月至 72 岁。PDA 的平均大小为 0.31±0.14 cm，平均 Qp/Qs 分流为 1.54±0.41，平均收缩期肺动脉压为 26.9±10.3 mmHg。线圈组有 10 例患者（1 名男孩和 9 名女孩），封堵器组有 1-5 例患者（4 名男孩和 11 名女孩）。PDA 封堵术后，ROCK 活性显著降低（1.78±2.25 对 0.77±0.69，p<0.01）。白细胞 ROCK 活性与收缩期 PA 压力之间存在强相关性（y = 5.4608x + 22.54，R2 = 0.5539，p<0.05），但与 Qp/Qs 值无关。两个亚组在手术后 ROCK 活性均有显著变化。有趣的是，比较线圈组和封堵器组时，封堵器组 ROCK 活性的降低更为明显。
本研究结果表明，PDA 患者的 ROCK 活性较高，且与 PA 压力相关。装置封堵后 ROCK 活性降低表明，ROCK 可能是 PDA 通畅性的重要生物标志物。
动脉导管未闭（PDA）；肺动脉压；Rho 激酶；经导管封堵术
