ABSTRACT
Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment.
Subject(s)
Hypertension, Pulmonary/drug therapy , Niflumic Acid/therapeutic use , Pulmonary Artery/drug effects , Pulmonary Circulation/physiology , Vascular Remodeling/drug effects , Animals , Arterioles/drug effects , Arterioles/pathology , Chloride Channels/antagonists & inhibitors , Disease Models, Animal , Hypertension, Pulmonary/pathology , Hypertension, Pulmonary/physiopathology , Muscle Tonus/drug effects , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Niflumic Acid/administration & dosage , Niflumic Acid/pharmacology , Pulmonary Artery/pathology , Pulmonary Artery/physiopathology , Rats, Sprague-Dawley , Tunica Media/drug effects , Tunica Media/pathologyABSTRACT
BACKGROUND: Patent ductus arteriosus (PDA) remains a common congenital heart disease in pediatric patients, and the new trend of catheterization therapy is still associated with some potential risks and complications. HYPOTHESIS: Compared with surgical closure, the clinical effect of catheterization therapy in pediatric PDA patients requires meta-analysis. METHODS: A systematic literature search of PubMed, Cochrane Library, Embase, Science Citation Index, Web of Science, and the Chinese Biomedicine literature database was conducted. Eligible studies included controlled trials of pediatric PDA patients receiving catheterization therapy vs surgical closure. Relative risks (RRs), standard mean differences, and 95% confidence intervals (CIs) were calculated and heterogeneity was assessed with the I(2) test. RESULTS: Seven studies with a total of 810 patients met the inclusion criteria. Catheterization therapy neither significantly increased the primary success rate (RR: 0.92, 95% CI: 0.82-1.03, P = 0.16) nor reduced the total postprocedure complications (RR: 0.74, 95% CI: 0.44-1.25, P = 0.26) and blood transfusion (RR: 1.10, 95% CI: 0.16-7.67, P = 0.93). Catheterization was associated with a statistically significant increase in residual shunts (RR: 5.19, 95% CI: 1.41-19.20, P = 0.01) and reduction in length of hospital stay (standard mean difference: -1.66, 95% CI: -2.65 to -0.67, P = 0.001). CONCLUSIONS: Catheterization therapy in pediatric PDA patients did not show a significant advantage in primary success rate, total complications, or blood transfusion, but it was associated with increase in residual shunts and reduction in length of hospital stay.
