Interventional Transcatheter Closure Ameliorates the Leukocyte Rho Kinase Activities among Patients with Patent Ductus Arteriosus

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Key words: Patent ductus arteriosus (PDA); Pulmonary arterial pressure; Rho kinase; Transcatheter closure.

Figure 1

Leukocyte Rho-associated coiled-coil containing protein kinase (ROCK) activity was reduced after catheter intervention on PDA (defined as the phosphorylation ratio of myosin binding subunit by Western blot measurement). PC, positive control lane; p-MBS, phospho-myosin binding subunit; t-MBS, total-myosin binding subunit.

Figure 2

The correlation between the leukocyte Rho-associated coiled-coil containing protein kinase (ROCK) activity and the systolic pulmonary artery pressure. Sys PAP, systolic pulmonary arterial pressure; p-MBS, phospho-myosin binding subunit; t-MBS, total-myosin binding subunit.

Figure 3

The correlation between the leukocyte Rho-associated coiled-coil containing protein kinase (ROCK) activity with the Qp/Qs value. p-MBS, phospho-myosin binding subunit; Qp/Qs, the ratio of pulmonary blood flow to systemic blood flow; t-MBS, total-myosin binding subunit.