Vascular Smooth Muscle Cell Apoptosis in Lungs Induction by Nitric Oxide in Congenital Heart Disease and Pulmonary Hypertension

Objectives Cell apoptosis was assessed in congenital heart disease by NO treatment in order to explore the molecular biological mechanism of pulmonary hypertension. Methods Total of 15 patients with congenital heart disease were selected from March to July in 2001. there were 10 male patients and 5 female patients, with age ranged from 0. 5 to 5 years old(mean 2. 9±1.5 years old). Patients were divided into 4 groups: Group 1 included 2 cases of ventricular septal defect and 4 cases of total atrioventricu-lar canal defect with severe pulmonary hypertension. Patients in group 1 were treated with inhalation of 5-10 ppm NO and pure oxygen 2-4 hours a day for 10 to 14 days. Heart rate, blood pressure and oxygen saturation are monitored. Group 2 included 2 cases of ventricular septal defect and 1 case of atrioventricular canal defect with severe pulmonary hypertension without inhalation of NO before operation. Group 3 included 3 cases of Tetrology of Fallot. Group 4 included 3 cases of atrial septal defect without pulmonary hypertension. During the operation, a 0. 5×0. 5 cm2 lung specimen was taken from the middle lobe of the right lung and was prepared to had HE stain, elastic stain, and TUNEL stain respectively. Results Groupl showed active apoptosis of smooth muscle cell in small artery after NO treatment before operation. Group 2 showed an obvious thickening of middle layer of the small artery and proliferation of elastic fiber and significant decrease of smooth muscle cell apoptosis. Group 3 showed no thickening of smooth muscle cell in small artery and no increase of cell apoptosis. Group 4 showed thinning and dilation of smooth muscle cell wall in small artery, no obvious elastic fiber and active apoptosis of smooth muscle cell in small artery. We proved that apoptosis of smooth muscle cell is decreased in patients with pulmonary hypertension but increased in patients with Tetrology of Fallot. Research of secondary pulmonary hypertension indicated that due to unbalance of cell proliferation and apoptosis caused by increase of cell proliferation, accumulation of cells would lead to pulmonary vascular remodeling. Conclusions Our study indicated that pulmonary hypertension may relate with decrease of smooth muscle cell apoptosis in molecular biological level. We speculated that NO can increase cell apoptosis and inhibits endothelial cell and smooth muscle cell over proliferation, thus inhibits pulmonary vascular remodeling.