The Effect of Sildenafil on Pulmonary Embolism-Induced Oxidative Stress and Pulmonary Hypertension

In Brief Acute pulmonary embolism (APE) is a major cause of pulmonary hypertension and death. We examined the effects of sildenafil on the hemodynamic changes caused by APE in anesthetized dogs. Sham-operated dogs (n = 3) received only saline. APE was induced by stepwise IV injections of 300 μm microspheres in amounts adjusted to increase mean pulmonary artery pressures by 20 mm Hg. Hemodynamic evaluation was performed at baseline, after APE was induced, and then after sildenafil 0.25 mg/kg (n = 8), or sildenafil 1 mg/kg + 0.3 mg · kg−1 · h−1 (n = 8) or saline (n = 9) infusions were started. Similar experiments were conducted to examine the effects of sildenafil in rat isolated perfused lung preparation. Plasma thiobarbituric acid reactive species were also determined in both studies to measure oxidative stress. Both doses of sildenafil reduced mean pulmonary artery pressures in dogs by approximately 8 to 16 mm Hg (both P < 0.05) and attenuated the increase in oxidative stress after APE. Mean arterial blood pressure remained unaltered after both doses of sildenafil. Sildenafil produced similar effects after APE in rat isolated perfused lung preparation. These findings indicate that IV sildenafil can selectively attenuate the increases in mean pulmonary artery pressures after APE, possibly through antioxidant mechanisms. IMPLICATIONS: We evaluated the effects of IV sildenafil in two animal models of acute pulmonary embolism. IV sildenafil selectively decreased pulmonary vascular resistance and pulmonary artery pressure and attenuated the increase in oxidative stress after acute pulmonary embolism in both models.