Sildenafil: Emerging Pulmonary Vasodilator for Pulmonary Hypertension due to Congenital Heart Disease

Pulmonary arterial hypertension is a life-threatening condition for which therapeutic options are limited. The current expensive gold standard-inhaled nitric oxide-is usually not affordable in developing countries. Moreover, nitric oxide has also not proved to be the single magic bullet for persistent pulmonary hypertension in newborn infants and those with complex congenital heart disorders. Nearly 20-30% of these cases do not respond to nitric oxide. Sildenafil (ViagraTM) a selective phosphodiesterase type 5 (PDE-5) inhibitor, primarily used to treat male erectile impotence, is under investigation as a novel therapy for this condition. PDE-5 is abundant in the lung and hydrolyses cyclic GMP, a mediator of vasorelaxation and antitrophic effects in vascular tissue. Chronic PDE5 inhibition has been shown to elevate pulmonary cyclic GMP levels and abrogate hypoxia-induced pulmonary hypertension and vascular remodeling in animal models, and to reduce pulmonary artery pressure in primary pulmonary hypertension. This article reviews the available evidence on the use of sildenafil for treating pulmonary hypertension in children with congenital heart disorders.