Study Of The Relationship Of The Pulmonary Micro-Arteriolar Pathological Grading And Serum Vascular Endothelial Growth Factor In Patients With Congenital Heart Disease Complicated By Pulmonary Hypertension

Objective: To assess the relationship of serum vascular endothelial growth factor (VEGF) and the pulmonary micro-arteriolar pathological grading and the effects of Prostaglandin Ei and Captopril on the concentrations of VEGF in patients with left-to-right shunting congenital heart disease complicated by pulmonary hypertension (PH).Methods: 47patients were selected from 82 patients, who were hospitalized from Jan.2000 to Jul.2004 with left-to-right shunting congenital heart disease, to be classified into 5 groups according to Heath-Edwards pathologic grading (VI grades): 8 patients of them belonged to grade I were named as group 1,10 patients with grade II as group 2, 13 patients with grade III as group 3, 9 patients with grade IV as group 4, and the other 7 patients with severe cyanosis belonged to grade V or even severe, than grade V as group 5. Allof the patients were infused with Prostaglandin E1 for 15 days with 10 ng/kg-min, 12 hours/day for 15 days. And Captopril was taken at the same time at the dose 0.5 mg/kg-d. Blood specimens were taken for studying from veins in the morning on the day before infusion, and on the 5th, 10th, 15th days respectively after infusion. Then the concentrations of VEGF were measured by enzyme linked immunosorbent assay (ELISA). The mean pulmonary artery pressure (MPAP) and the pulmonary vessel resistance (PVR) were measured in all of the cases. The biopsy specimens of lungs were taken to measure mean medial thickness in pulmonary arterioles (mMTPA), the relative ratios of vessel wall area/total area (WA/TA), the relative ratios of vessel lumen area/total area (EA/TA) and the percentage of thick walled peripheral lung vessel (TWPV).Results: With the increasing of pathological grades of pulmonary vessel, the serum VEGF concentration, MPAP, PVR, mMTPA, WA/TA and TWPV gradually increased, while EA/TA gradually decreased. For all indexes above, there were significant differences between group 1 and group 2, group 2 and group 3, group3 and group 4, group 4 and group 5(P<0.01). When the pathologic grad were less than grad III, the correlation analysis revealed that the serum VEGF concentration were positively correlated with MPAP, PVR, mMTPA, WA/TA, TWPV, but negatively correlated with EA/TA (P<0.0l). The concentrations of VEGF increased from group 1 to group 3, and got to a peak value in group 3, but decreased from group4 to group 5. And it decreased acutely in group 5. However, the concentrations of VEGF didn't decrease obviously after medication in group 1 ( P>0.05) ,but in group 2 and group 3, the concentrations of VEGF decreased obviously at the 5th day, and maintained the lower level at the 10th and 15th day ( P<0.01) , and changed a little in group4 ( P<0.05 ) , but the concentrations of VEGF didn't change any more in group 5 ( P>0.05) .Conclusion: There was a close relationship between the serum VEGF concentration and the pathological grades of pulmonary vessel; Prostaglandin E1 and captopril can lower VEGF, but the extent relates to the pulmonary micro-arteriolar pathological grading intently.