合并室间隔缺损的大动脉转位所致肺动脉高压的可逆性程度及其分子机制

Objective Explore the reversibility and potential molecular mechanisms of pulmonary hypertension in pa-tients with complete transposition of the great arteries (cTGA) combined with ventricular septal defect (VSD) in comparison with those with simple VSD. Methods Twenty-four patients with pulmonary hypertension (mean pulmonary arterial pressure was greater than 30 mmHg) were enrolled in our study, in which 10 patients suffered from cTGA with VSD, and the rest 14 pa-tients suffered from simple VSD. Lung specimens were taken from the right middle lobe of lung before cardiopulmonary bypass. The extent of pulmonary hypertension was then graded according to the Heath-Edwards classification. ELISA was used to exam-ine the expression of eNOS, iNOS, ET-1, ET-AR, ET-BR, MMP-2, MMP-9 and TIMP in all the specimens. Results No statistically significant differences in age, height, weight, the size of VSD, and the pulmonary artery pressure before operation were found between the groups. The level of hemoglobin, aortic and pulmonary arterial oxygen saturation, and the reduction value of pulmonary arterial pressure after surgery were significantly higher in the cTGA patients than that in the simple VSD pa-tients (P < 0.05). All patients had grade 0 - Ⅱ Heath-Edwards changes in their lung biopsy samples. The expression of eNOS and MMP-2 was significantly lower in the TGA group than that in the simple VSD group [eNOS: (280.13 ± 101.92) ng/mg vs. (488.41±249.6) ng/mg, P<0.05; MMP-2:(31.68±15.36)ng/mg vs. (69.28±49.12)ng/mg, P<0.05]. There were no statistically significant differences between the two groups regarding the expression of iNOS, ET-1, ET-AR, ET-BR,MMP-9 or TIMP. Conclusion The imbalance of the NOS/ET system and the MMP/TIMP system involves in the development of pulmonary hypertension in patients with TGA combined with VCD. In patients with cTGA, the high oxygenation state in pul-monary circulation may decrease the expression of MMP2 and eNOS, and may affect the progress of pulmonary hypertension to a certain extent.

Reversibility and molecular mechanisms of pulmonary hypertension in patients with complete transposition of the great arteries combined with ventricular septal defect