Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension

Objective: To determine whether inhalation of aerosolized sildenafil with a nd without inhaled nitric oxide (NO) causes selective pulmonary vasodilatio n in a sheep model of pulmonary hypertension. Design: A controlled laboratory study in instrumented, awake, spontaneously breathing lambs. Setting: Animal research laboratory affiliated with a university hospital. Subject: Twenty Suffolk lambs. Interventions: Lambs were instrumented with a carotid artery catheter, a pu lmonary artery catheter, and a tracheostomy tube and studied awake. After b aseline measurements, pulmonary hypertension was induced by the continuous infusion of U46619, a thromboxane A(2) analog. After breathing three concen trations of inhaled NO (2, 5, and 20 ppm), lambs were divided into two grou ps. Group 1 (n = 7) breathed aerosols containing 1, 10, and 30 mg of silden afil alone, and group 2 (n = 4) simultaneously breathed NO (2 and 5 ppm) an d aerosols containing 10 mg of sildenafil. Hemodynamic measurements were ob tained before and at the end of each drug administration. Venous admixture was calculated, and plasma cyclic guanosine monophosphate and sildenafil co ncentrations were measured. Measurements and Main Results: Aerosols containing 10 mg and 30 mg of silde nafil selectively decreased the pulmonary artery pressure by 21% +/- 3% and 26% +/- 3%, respectively (p < .05 vs. baseline pulmonary hypertension). Wh en 10 mg of sildenafil was inhaled while simultaneously breathing 2 ppm and 5 ppm NO, the pulmonary artery pressure decreased by 35% +/- 3% and 43% +/ - 2% (p < .05 vs. baseline pulmonary hypertension). Inhaled sildenafil did not impair systemic oxygenation, increase right-to-left intrapulmonary shun ting, or impair the ability of inhaled NO to reduce right-to-left shunting. Conclusions: Nebulized sildenafil is a selective pulmonary vasodilator that can potentiate the pulmonary vasodilating effects of inhaled NO.