Korean J Pediatr 2010;53(6):688-693 • DOI: 10.3345/kjp.2010.53.6.688 691 Treatment of PH in the BPD patients Most patients with PH showed gradual resolution of PH over the first year of life because the damaged lung recovered and normal alveolarization completed. However, because some BPD patients with severe PH could experience fatal right heart failure and other complications from PH6-9), meticulous and aggressive treatment of PH in the BPD patients is mandatory. The basis of the treatment of PH in the BPD patients is to correct the underlying lung disease. These underlying conditions include chronic gastroesophageal reflux and aspiration, airway problems, such as laryngotracheomalacia, subglottic stenosis, and vocal cord palsy, and other conditions that cause intermittent or persistent hypoxia12). In case of repairable anatomic lesions to contribute to the PH, aggressive correction should be performed because the reduced vascular surface area in the BPD patients may result in significant hemodynamic injury caused by even a relatively small increase of left-to-right blood shunt through the patent foramen ovale, atrial septal defect, patent ductus arteriosus, or even other systemic-to-pulmonary collateral vessels12). Oxygen supply is the mainstay of the medical treatment of PH in the BPD patients. Chronic hypoxia can induce pulmonary vascular constriction and aggravate PH, while sufficient oxygenation can be helpful in the recovery of damaged pulmonary tissue and normal growth of the lung. In this regard, oxygen saturation (SpO2) should be maintained at more than 93-95% in the patients with BPD23). The oxygen supply should be discontinued when the SpO2 is greater than 93~95% without oxygen supply. In particular, the BPD patients with PH should have an SpO2 in the mid-90%24, 25). Besides oxygen supply, some BPD patients with PH require selective pulmonary vasodilators to decrease pulmonary arterial pressure; these medications subsequently decrease RV afterload and increase cardiac output from the RV. These actions result in an improvement of left ventricular filling and increase of systemic blood pressure and coronary perfusion26). The currently used medications for selective pulmonary vasodilation include inhaled nitric oxide (NO), inhaled prostacyclins, sildenafil, and endothelin-receptor antagonist. These medications can dilate the pulmonary artery and decrease the RV afterload through different mechanisms. Inhaled NO selectively decreases pulmonary vascular resistance and increases systemic venous oxygen saturation by improving ventilation–perfusion match27). Inhaled NO improves oxygenation in infants with known BPD28) and may be useful for long- term treatment of pulmonary hypertension29). Although long- term inhaled NO treatment has been used in the BPD patients, especially those who require continuous mechanical ventilation, no study has reported such data to date. Preventive low-dose inhaled NO supply can reduce the incidence of BPD in the preterm infants with birth weight greater than 1,000 g, but it showed no effect in the infants with birth weight less than 1,000 g. Therefore, the use of preventive inhaled NO for BPD prevention is questionable30, 31). Most patients require an initial inhaled NO dose of 10-20 parts per million (ppm) for PH treatment and a maintenance dose of 2-10 ppm for weaning. Because sudden discontinuance of inhaled NO may cause rebound PH, other selective pulmonary vasodilators should be started before the discontinuance of inhaled NO even though the patient’s condition is good32). Inhaled prostacyclin is less expensive and more readily available than inhaled NO in the centers with NICU. Aerosolized prost- acyclin may be administered directly to the lung, and it causes vasodilation in the ventilated pulmonary regions; it therefore minimizes the systemic side effects and helps avoid catheter- related complications in the patients33). Inhaled iloprost is the representative prostacyclin derivative; it easily dissolves in normal saline and has a lower viscosity than other prostacyclin derivatives34). The potential effect of inhaled iloprost for improving PH in the pediatric group has been established35). A case study had reported an improvement caused by inhaled iloprost in the BPD patient with severe PH36). For ensuring adequate improvement, inhalation should be performed 6-9 times a day because the half-life of the prostacyclin is extremely short. The occurrence of occasional bronchospasm may be a restricting factor in the use of inhaled prostacyclins by the BPD patients35). Sildenafil, a highly selective phosphodiesterase type-5 inhibitor, increases cyclic GMP in the pulmonary vascular smooth muscle cells and decreases pulmonary vascular resistance. The effect of sildenafil has been well proven in the patients with RV failure caused by PH32). Sildenafil also has a synergistic effect with other pulmonary vasodilators, such as inhaled NO and inhaled iloprost, which have different pharmacologic mechanisms10, 37). A recent study on BPD patients with PH also showed that the use of sildenafil was safe and provided long-term beneficial effect38). The recommended starting dose of sildenafil is 0.5 mg/kg every 8 h. If the patient shows no systemic hypotension, the dose can be gradually increased to get the desired effect or up to 2 mg/kg every 6 h over 2 weeks12). Endothelin-receptor antagonist inhibits the effect of endo- thelin-1, which is a potent vasoconstrictor, and induces pulmonary vascular smooth muscle cell hyperplasia12, 39). Bosentan is a representative non-selective endothelin-receptor antagonist that is orally administered. Bosentan improves exercise capacity of the